A Phase 1, First-in-Human, Open-label Single Agent Study of SUPLEXA Therapeutic Cells in Patients With Metastatic Solid Tumours and Haematologic Malignancies
Phase: PHASE1
Conditions: Oncology
Sponsor: Alloplex Biotherapeutics Inc

CLINICAL STUDY PROTOCOL 
 
Protocol Title:  
A Phase 1, First-in-Human, Open-label Single Agent Study of SUPLEXA 
Therapeutic Cells in Patients with Metastatic Solid Tumours and Haematologic 
Malignancies 
Protocol Number:  
SUPLEXA-101 
Study Intervention:  
SUPLEXA Therapeutic cells, a single agent autologous adoptive cellular 
immunotherapy derived from patient peripheral blood mononuclear cells (PBMC) 
Study Phase:  
1 
Clinical Sites 
Up to 4 sites in Australia 
Sponsor Name: 
Alloplex Australia Pty. Ltd. 
Legal Registered Address: 
58 Gipps St, Collingwood, VIC 3066, Australia 
Version: 
4.0, Amendment 3 
Approval Date: 
30 Sep 2022 
NCT: 
NCT05237206 
 
 

 
Protocol Number: SUPLEXA-101 
 
Study intervention: SUPLEXA Therapeutic cells 
 
 
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CLINICAL STUDY PROTOCOL 
 
Protocol Title:  
A Phase 1, First-in-Human, Open-label Single Agent Study of 
SUPLEXA Therapeutic Cells in Patients with Metastatic Solid 
Tumours and Haematologic Malignancies 
Protocol Number:  
SUPLEXA-101 
Study Intervention:  
SUPLEXA Therapeutic cells, a single agent autologous adoptive 
cellular immunotherapy derived from patient peripheral blood 
mononuclear cells (PBMC) 
Study Phase:  
1 
Clinical Sites 
Up to 4 sites in Australia 
Sponsor Name: 
Alloplex Australia Pty. Ltd. 
Legal Registered 
Address: 
58 Gipps St, Collingwood, VIC 3066, Australia 
Version: 
4.0, Amendment 3 
Approval Date: 
30 Sep 2022 
 
 
 
 
 
Confidentiality Notice 
This document contains confidential information of Alloplex Australia Pty. Ltd. the 
contents of which must not be disclosed to anyone other than the study staff and members 
of the respective Institutional Review Board/Ethics Committee. 
The information in this document cannot be used for any purpose other than the evaluation 
or conduct of the clinical investigation without the prior written consent of Alloplex 
Australia Pty. Ltd. 
 
 

 
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SPONSOR SIGNATORY 
Protocol Title:  
A Phase 1, First-in-Human, Open-label Single Agent Study of 
SUPLEXA Therapeutic Cells in Patients with Metastatic Solid 
Tumours and Haematologic Malignancies 
Protocol Number:  
SUPLEXA-101 
Version and Date: 
4.0, 30 Sep 2022 
Amendment No.  
Amendment 3 
 
The above titled study protocol was subjected to critical review. The information presented is 
consistent with current knowledge of the risks and benefits of the investigational product, as well 
as with the moral, ethical, and scientific principles governing clinical research as set out in the 
current Declaration of Helsinki and the guidelines on Good Clinical Practice. 
 
 
 
Frank Borriello, MD, PhD, CEO 
 
Date 
 
 
Sharron Gargosky, PhD, CDO 
 
Date 
 
 
 
Sponsor Medical Monitor Name and Contact Information: 
Frank Borriello, MD, PhD  
Founder & Chief Executive Officer 
Alloplex Biotherapeutics, Inc. 
300 Tradecenter Drive - Suite 6580, Woburn, MA 01801 
Email: fborriello@alloplexbio.com 
Phone: 857-272-1214 (m) 
 
 

 
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DOCUMENT HISTORY 
DOCUMENT HISTORY 
Document 
Date 
Protocol Version 4.0, Amendment 3 
30 September 2022 
Protocol Version 3.0, Amendment 2 
18 May 2022 
Protocol Version 2.2, Amendment 1.2 
28 December 2021 
Protocol Version 2.1, Amendment 1.1 
30 November 2021 
Protocol Version 2.0, Amendment 1.0 
09 November 2021 
Original Protocol, Version 1.0 
21 September 2021 
Version 4.0 Amendment 3; 30   Sept 2022 
Overall Rationale for the Amendment: 
Summary of Changes (in order of appearance) 
Section Number and 
Name 
Description of Change 
Rationale for Change 
1.1 Synopsis 
1.2 Study Schema 
1.3 Schedule of Activities 
4.1 Overall Study Design 
6 Study Intervention 
• Extend treatment duration in subjects 
deriving clinical benefit.  
• Add description about manufacturing a 
second batch of SUPLEXA cells to 
ensure there is sufficient supply for 
treatment extension.  
• Added additional doses after dose 3 is 
5B cells every 2 weeks unless only a 
single dose available to be given. 
• For ethical reasons based on 
emerging data from ongoing 
study that further supports 
the original nonclinical data 
that up additional SUPLEXA 
doses can be safely 
administered. 
1.1 Synopsis 
1.3 Schedule of Activities 
4.1 Overall Study Design 
10.6 (Appendix 6) 
iRECIST 
• Add iRECIST for disease evaluation in 
solid tumours  
• To define progressive disease 
on iRECIST evaluation in 
order to address the 
possibility of pseudo 
progression. 
1.1 Synopsis 
1.3 Schedule of Activities 
4.1 Overall Study Design 
5.1 Inclusion Criteria 
• Add optional tumour biopsies of solid 
tumour patients where clinically feasible.  
• To allow assessment of 
tumour microenvironment 
following therapy. 
1.1 Synopsis 
4 Study Design 
6.1 Study Intervention 
Administered 
• Clarify that a dose unit of 2.5 billion 
cells / 100mL is an approximate number 
and that the range of cells can vary from 
1.9 to 3.1 billion cells for any particular 
SUPLEXA batch. 
• For clarity. 
1.1 Synopsis 
4 Study Design 
4.1.3 Follow Up 
• PFS and OS follow up is every 8 weeks 
for 48 weeks post last SUPLEXA dose.  
• To simplify follow up to 48 
weeks post last SUPLEXA 
dose due to variable dosing. 

 
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Section Number and 
Name 
Description of Change 
Rationale for Change 
1.1 Synopsis 
6.5 DLT period 
 
• DLT addressed in initial enrolment of > 
12 patients and thus removed. 
• Due to safety profile of 
autologous therapies and 
SUPLEXA, DLT window is 
not necessary 
1.1 Synopsis 
4.1 Overall Study Design 
7.3 Subject Withdrawal 
from the Study 
• Clarify that if a subject permanently 
discontinues study intervention and 
initiates another anti-cancer therapy, the 
subject will be withdrawn from the 
study. 
• For clarity. 
1.1 Synopsis 
4.1 Overall Study Design 
• Focus the remainder of the study on 
selected solid tumours. 
• To focus on solid tumours of 
interest based on preclinical 
and clinical findings. 
1.1 Synopsis 
9.1 Sample size 
determination 
• Increase sample size to 60 subjects and 
define cancer types.  
• To identify tumour types 
most likely to respond to 
therapy and find an active 
dose levels with a safe 
profile. 
2.3 Benefit and Risks 
Analysis 
• Update based on emerging data from 
ongoing study. 
• To update safety profile 
based on clinical data.  
3 Objectives and 
Endpoints 
• Add iRECIST as exploratory 
objectives/endpoints. 
• Assessment was added as 
part of disease evaluation to 
address pseudo-progression. 
4.3 Dose Justification 
• Update to support treatment extension. 
• To support treatment 
extension in patients deriving 
benefit. 
5.1 Inclusion Criteria 
• Clarify inclusion criterion no. 4 
regarding washout periods prior to 
drawing initial blood for SUPLEXA 
production and prior to SUPLEXA 
dosing. 
• To clarify. 
5.2 Exclusion Criteria 
6.8 Concomitant Generic 
Therapy 
• Revise exclusion criterion 14 to allow 
stable dose of low-level steroid. 
 
• To accommodate standard 
clinical practice. 
6.0 Study Intervention 
• Post administration observation period 
for additional doses. 
• To address observation 
period post infusion for 
additional doses. 
6.8 Concomitant Generic 
Therapy 
6.8.2 Prohibited 
Medications and 
Treatments 
• Clarify language relating to 
immunosuppressive anticancer therapies. 
• To clarify.  
8.4 Pharmacodynamic 
measures 
• Clarify language around blood and 
PBMC sample analysis 
• To clarify. 

 
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Section Number and 
Name 
Description of Change 
Rationale for Change 
9.3.6 Data Safety 
Monitoring Board 
• Changes IDMC to DSMB 
• To clarify.  
• Same independent clinical 
panel just changed for 
consistency of 
documentation. 
General 
• Correct typographical errors, 
hyperlinks/cross-references, style, and 
formatting (not tracked) 
• Align across protocol sections 
• Update protocol section numbering 
• Update footer with version and date 
• For consistency and clarity 
• Alignment across protocol 
 
 
 
 
 

 
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CLINICAL STUDY PROTOCOL ...............................................................................................1 
SPONSOR SIGNATORY .............................................................................................................2 
PRINCIPAL INVESTIGATOR SIGNATURE PAGE ............... ERROR! BOOKMARK NOT 
DEFINED. 
DOCUMENT HISTORY ..............................................................................................................3 
LIST OF TABLES .........................................................................................................................9 
LIST OF FIGURES .......................................................................................................................9 
1 
PROTOCOL SUMMARY ..............................................................................................10 
1.1 
SYNOPSIS ............................................................................................................................10 
1.2 
SCHEMA ..............................................................................................................................17 
1.3 
SCHEDULE OF ACTIVITIES ...................................................................................................19 
2 
INTRODUCTION............................................................................................................27 
2.1 
STUDY RATIONALE .............................................................................................................27 
2.2 
BACKGROUND .....................................................................................................................28 
2.2.1 Study Intervention Overview .............................................................................................29 
2.3 
BENEFIT AND RISK ANALYSIS .............................................................................................30 
2.3.1 Risk Assessment ................................................................................................................30 
2.3.2 Benefit Assessment ............................................................................................................32 
2.3.3 Overall Benefit: Risk Conclusion ......................................................................................32 
3 
OBJECTIVES AND ENDPOINTS ................................................................................33 
4 
STUDY DESIGN ..............................................................................................................35 
4.1 
OVERALL STUDY DESIGN ...................................................................................................35 
4.1.1 Screening Period – All Subjects ........................................................................................35 
4.1.2 Treatment Period ................................................................................................................36 
4.1.3 Follow-up – All Subjects ...................................................................................................38 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN .......................................................................38 
4.3 
DOSE JUSTIFICATION FOR SUPLEXA THERAPEUTIC CELL DOSE .......................................39 
4.4 
STUDY DURATION ...............................................................................................................39 
5 
ELIGIBILITY CRITERIA .............................................................................................40 
5.1 
INCLUSION CRITERIA ..........................................................................................................40 
5.2 
EXCLUSION CRITERIA .........................................................................................................41 
5.3 
SCREEN FAILURES...............................................................................................................44 
6 
STUDY INTERVENTION ..............................................................................................45 
6.1 
STUDY INTERVENTION ADMINISTERED ...............................................................................45 

 
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6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY .....................................................46 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING ......................................46 
6.4 
STUDY INTERVENTION COMPLIANCE ..................................................................................46 
6.5 
DOSE LIMITING TOXICITY CRITERIA ...................................................................................47 
6.5.1 Dose Modifications and Individual Stopping Rules due to DLT ......................................48 
6.6 
TOXICITY MANAGEMENT ....................................................................................................51 
6.7 
TREATMENT OF OVERDOSE .................................................................................................51 
6.8 
CONCOMITANT GENERIC THERAPY.....................................................................................51 
6.8.1 Prophylaxis ........................................................................................................................52 
6.8.2 Prohibited Medications and Treatment ..............................................................................52 
6.8.3 Rescue Medications and Supportive Care .........................................................................53 
7 
STOPPING RULES, DISCONTINUATION OF STUDY INTERVENTION 
AND SUBJECT WITHDRAWAL FROM THE STUDY ............................................54 
7.1 
STUDY STOPPING RULES .....................................................................................................54 
7.2 
DISCONTINUATION OF STUDY INTERVENTION .....................................................................54 
7.2.1 Immunological effects: Action and Follow-Up Assessment .............................................55 
7.2.2 Pregnancy ...........................................................................................................................55 
7.3 
SUBJECT WITHDRAWAL FROM THE STUDY .........................................................................55 
7.4 
LOST TO FOLLOW UP ...........................................................................................................56 
8 
STUDY ASSESSMENTS AND PROCEDURES ..........................................................57 
8.1 
EFFICACY ASSESSMENTS ....................................................................................................57 
8.1.1 RECIST v1.1 (Solid Tumours Cohort only) ......................................................................57 
8.1.2 Disease Response Assessments (Haematologic Malignancies Cohort only) ....................57 
8.2 
SAFETY ASSESSMENTS ........................................................................................................57 
8.2.1 Physical Examinations .......................................................................................................57 
8.2.2 Vital Signs ..........................................................................................................................58 
8.2.3 Electrocardiograms ............................................................................................................58 
8.2.4 Clinical Safety Laboratory Assessments ...........................................................................58 
8.2.5 Performance Status ............................................................................................................59 
8.3 
ADVERSE EVENTS (AES), SERIOUS ADVERSE EVENTS (SAES), AND OTHER SAFETY 
REPORTING .........................................................................................................................60 
8.3.1 Time Period and Frequency for Collecting AE and SAE Information ..............................61 
8.3.2 Method of Detecting AEs and SAEs .................................................................................61 
8.3.3 Follow-up of AEs and SAEs ..............................................................................................61 
8.3.4 Regulatory Reporting Requirements for SAEs ..................................................................62 
8.3.5 Pregnancy ...........................................................................................................................62 
8.3.6 Disease Progression ...........................................................................................................62 
8.3.7 Death Events ......................................................................................................................63 
8.4 
PHARMACODYNAMICS AND CORRELATIVE BIOMARKERS ...................................................63 

 
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9 
STATISTICAL CONSIDERATION .............................................................................64 
9.1 
SAMPLE SIZE DETERMINATION ...........................................................................................64 
9.2 
POPULATION FOR ANALYSES ..............................................................................................64 
9.3 
STATISTICAL METHODS ......................................................................................................64 
9.3.1 General ...............................................................................................................................64 
9.3.2 Efficacy Analysis ...............................................................................................................65 
9.3.3 Safety and Tolerability Analysis ........................................................................................66 
9.3.4 Other Analyses ...................................................................................................................66 
9.3.5 Interim Analysis .................................................................................................................66 
9.3.6 Data Safety Monitoring Board (DSMB) ............................................................................66 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS .......................................................................................................67 
10.1 
APPENDIX 1: REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS ............67 
10.1.1 Regulatory and Ethical Considerations ..............................................................................67 
10.1.2 Financial Disclosure...........................................................................................................68 
10.1.3 Informed Consent Process .................................................................................................68 
10.1.4 Data Protection...................................................................................................................69 
10.1.5 Dissemination of Clinical Study Data................................................................................69 
10.1.6 Data Quality Assurance .....................................................................................................69 
10.1.7 Source Documents .............................................................................................................70 
10.1.8 Study and Site Start and Closure .......................................................................................70 
10.1.9 Publication Policy ..............................................................................................................71 
10.2 
APPENDIX 2: CLINICAL LABORATORY TESTS ......................................................................72 
10.3 
APPENDIX 3: AES AND SAES: DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING ......................................................................73 
10.3.1 Definition of AE ................................................................................................................73 
10.3.2 Definition of SAE ..............................................................................................................74 
10.3.3 Recording and Follow-Up of AE and/or SAE ...................................................................75 
10.3.4 Reporting of SAEs .............................................................................................................78 
10.4 
APPENDIX 4: CONTRACEPTIVE GUIDANCE AND COLLECTION OF PREGNANCY 
INFORMATION .....................................................................................................................79 
10.4.1 Definitions..........................................................................................................................79 
10.4.2 Contraception Guidance.....................................................................................................79 
10.4.3 Collection of Pregnancy Information.................................................................................81 
10.5 
APPENDIX 5: SUMMARY OF RESPONSE EVALUATION CRITERIA IN SOLID TUMOURS 
(RECIST) V1.1 ...................................................................................................................83 
10.5.1 RECIST v1.1 ......................................................................................................................83 
10.5.2 Radiographic Imaging as Basis for Methods of Measurement ..........................................86 
10.6 
APPENDIX 6:  MODIFIED RECIST V1.1 FOR IMMUNE-BASED THERAPEUTICS .....................87 
10.7 
APPENDIX 7: CRS TOXICITY TREATMENT GUIDELINES ......................................................90 
10.8 
APPENDIX 8: TLS TOXICITY MANAGEMENT .......................................................................91 

 
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10.9 
APPENDIX 9: GUIDANCE TO ADDRESS GLOBAL HEALTH EMERGENCIES AND POTENTIAL 
IMPACT ON THE CLINICAL STUDY .......................................................................................94 
10.10 APPENDIX 10: GLOSSARY ...................................................................................................97 
10.11 APPENDIX 11: PROTOCOL AMENDMENT HISTORY ............................................................100 
REFERENCES ...........................................................................................................................103 
 
LIST OF TABLES 
Table 1: 
Potential Risks and Mitigation Strategy ....................................................31 
Table 2: 
Eastern Cooperative Oncology Group (ECOG) Performance Status ........59 
Table 3: 
Karnofsky Performance Status ..................................................................60 
Table 4: 
Adverse Event Reporting Periods and Reporting Timelines to the 
Sponsor ......................................................................................................61 
Table 5: 
Clinical Safety Laboratory Tests ...............................................................72 
Table 6: 
Contraception Methods Acceptable for this Study ....................................81 
Table 7: 
Modified MD Anderson (MDA) Criteria for Bone Metastases+...............85 
Table 8: 
Overall Time Point Response Assignment at Subsequent Assessments ...85 
Table 9 
 iRECIST Time Point iResponse ...............................................................88 
Table 10: 
Recommendation for Prevention and Treatment of Tumour Lysis 
Syndrome ...................................................................................................93 
 
LIST OF FIGURES 
Figure 1: 
Study Schema – Screening and Manufacturing Period (Day -35 to Day 
1) in All Subjects .......................................................................................17 
Figure 2: 
Study Schema – Overview (minimally 3 doses) ........................................18 
Figure 3: 
SUPLEXA Manufacturing Overview ........................................................27 
Figure 4: 
SUPLEXA Mechanism of Action Overview .............................................29 
Figure 5: 
Individual DLT Stopping Rules and Dose Modification of Study 
Intervention ................................................................................................50 
Figure 6: 
TLS risk assessment of solid tumours, myelomas and chronic 
leukaemias..................................................................................................92 
 
 

 
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1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS 
Protocol Title: A Phase 1, First-in-Human, Open-label Single Agent Study of SUPLEXA 
Therapeutic Cells in Patients with Metastatic Solid Tumours and Haematologic Malignancies 
Short Title: Phase 1 Study of SUPLEXA in Patients with Metastatic Solid Tumours and 
Haematologic Malignancies 
Rationale 
SUPLEXA Therapeutic cells (referred to as SUPLEXA throughout this protocol) are a 
heterogeneous mixture of PBMC-derived activated white blood cells, comprised predominantly 
of natural killer (NK) cells, natural killer T (NKT) cells, gamma/delta () positive T cells, and 
alpha/beta () positive T cells of both the cytotoxic CD8-positive and CD4-positive T 
lymphocytes (CTL) variety. All cell types have individually been shown by other researchers to 
contribute to the anti-tumour response. SUPLEXA cells have the ability to rapidly lyse a variety 
of tumour lines at exceedingly low effector to target cell ratios in an in vitro functional cytolysis 
assay. Moreover, flow sort data reveal that the cytolytic activity resides in both the 
CD56-positive (NK cell population) as well as the CD56-negative populations (T cell 
population), indicating that a minimum of two distinct SUPLEXA subpopulations possess anti-
tumour activity. 
SUPLEXA has been demonstrated to show anti-tumour activity on all tumour cell line tested to 
date irrespective of origin (e.g., melanoma, colorectal, breast, prostate, leukemia, glioma, 
ovarian, renal, glioma, and leukemia), while simultaneously showing no adverse impact on 
normal resting peripheral blood mononuclear cells (PBMC) derived from either allogeneic or 
autologous sources, suggesting that resting normal naïve immune cells are not targeted by 
SUPLEXA. Additionally, SUPLEXA demonstrates no fratricide, indicating that normal activated 
immune cells are not targeted either. 
During manufacturing, expanding SUPLEXA are supported by cytokines interleukin (IL)-7 and 
IL-15. After formulation in cryogenic media, controlled freezing, storage under liquid nitrogen, 
and controlled thawing, SUPLEXA remain highly efficacious against tumour targets. 
Additional nonclinical studies in organoids, as well as mouse patient derived xenografts (PDX) 
and xenograft models support the anti-tumour activity of SUPLEXA, as follows: 
1) Champions Oncology conducted two human organoid studies, (1) lung cancer cells and 
(2) colorectal cancer cells, to show that SUPLEXA cells display a highly statistically 
significant result within the first 24 hours post-thaw. 
2) Charles River conducted a xenograft study with a melanoma xenograft using a single low 
dose of SUPLEXA cells alone and found a statistically significant difference between the 
treated and untreated groups. SUPLEXA was safe and well tolerated. 
3) Crown Bio conducted lung cancer PDX studies. The study used a repeat SUPLEXA 
dosing strategy and showed a statistically significant difference between the treated and 
untreated groups. Once again, SUPLEXA was safe and tolerated well. 
This Phase 1, first-in-human (FIH), open-label study is designed to assess the safety, tolerability, 
and preliminary clinical efficacy of repeated intravenous (IV) infusions of SUPLEXA 

 
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monotherapy in subjects with measurable metastatic solid tumours and haematologic 
malignancies. 
Objectives and Endpoints (Primary and Secondary) 
Objectives 
Endpoints 
Primary 
 
• To assess safety and tolerability of 
SUPLEXA in subjects with malignant 
solid tumours and haematologic 
malignancies. 
• Incidence of dose limiting toxicities 
(DLTs) (as described in Section 6.5.1. 
• Incidence of adverse events (AEs), and 
serious adverse events (SAEs) overall, by 
severity, by relationship to each study 
intervention, and those that led to 
discontinuation of study intervention. 
Secondary 
 
• Solid tumours cohort: To assess the 
efficacy of SUPLEXA in subjects with 
malignant solid tumour as assessed by the 
Investigator based on response evaluation 
criteria in solid tumours (RECIST) v1.1 or 
by changes in tumour-derived blood 
biomarkers. 
• Objective response rate (ORR) defined as 
the proportion of subjects with best 
overall response (BOCR) of either a 
complete response (CR) or partial 
response (PR). 
• Time to Progression (TTP). 
• Haematologic malignancies cohort: To 
assess the efficacy of SUPLEXA in 
subjects with haematologic malignancies 
(multiple myeloma, lymphoma, and 
chronic lymphocytic leukemia). 
• Objective response rate as defined by 
standard of care. 
Overall Design 
This is a FIH Phase 1, non-comparative, open-label, basket-design study. The study will consist 
of 2 cohorts: 
• Solid tumours cohort: This cohort will include subjects with histologically or cytologically 
confirmed measurable solid tumours (e.g., various squamous cell carcinomas (skin, cervical, 
vaginal, oesophageal, lung), melanoma, prostate, and breast cancer)), radiographically 
confirmed as Stage 2 to 4 cancer. Subjects must fulfill entry criteria and not be currently 
receiving or under the residual influence of immunosuppressive therapies. 
• Haematologic malignancies cohort: This cohort will include subjects with histologically or 
cytologically confirmed multiple myeloma, lymphoma, and chronic lymphocytic leukemia 
(collectively termed as haematologic malignancies for the purposes of this protocol). 
Subjects must fulfill entry criteria and have relapsed or refractory advanced malignancy for 
which no standard therapy exists. 

 
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A Data Safety Monitoring Committee (DSMB) will provide oversight of the study and will 
monitor safety on a regular basis throughout the study to recommend on any modification of the 
study. Refer to Section 9.3.6. 
The study will be comprised of 3 periods. Screening, Treatment and Follow-up. Throughout the 
study, subjects will be evaluated as specified in the Schedule of Activities (SoA) in Section 1.3. 
Study schema is provided in Figure 2. 
Screening Period – All Subjects 
Prior to enroling in the study, and before performance of any procedures, potential subjects will 
attend a Screening session where they will be provided with full information concerning details 
of the study assessments and procedures. They will also be provided with a Participant 
Information Sheet and Informed Consent Form (PICF). Prior to being required to sign the 
consent form, subjects will be given time to review study information and ask questions. 
After signing the PICF, potential candidates will undergo screening procedures over 2 visits 
during a Screening period lasting up to 5 weeks (Section 1.2, Figure 1). During Screening 
Visit 1, blood will be drawn for safety laboratory assessment (~5 mL), for processing and 
manufacturing of SUPLEXA batch 1 (~50 mL of whole blood) and for exploratory studies 
(~20 mL of whole blood). Subjects who meet the safety laboratory inclusion criteria and have 
adequate evidence of blast formation at the manufacturing facility (notification of status will 
require 5 days from the initiation of culture), will proceed to Screening Visit 2. Subjects in whom 
the SUPLEXA blast formation does not occur will be considered screen failures and be replaced. 
This is expected to be < 10 % of subjects. 
Standard of care tests/procedures that were performed prior to signing the consent can be used as 
part of the screening assessments if the procedures meet the protocol-required timelines (i.e., 
within 5 weeks of consent) and it is documented in the source documents that these procedures 
performed prior to signing the consent were standard of care procedures. 
Eligibility criteria for study entry will be assessed locally by the Investigator; for the solid 
tumour cohort, screening radiographic scans (within 5 weeks of consent) will be collected and 
held for possible future retrospective evaluation by Sponsor or blinded independent central 
review (BICR). Safety laboratory assessments of all subjects will be rechecked for eligibility on 
the day of the first treatment with the local hospital laboratory (and the central laboratory for 
documentation), prior to first dose with study intervention. 
Treatment Period  
All eligible subjects will initially receive approximately weekly dosing of SUPLEXA, with a 
target of 2.5B cells per dose (range of 1.9 to 3.1 billion cells) per dose. 
Dosing will be done as follows: 
• First 3 SUPLEXA infusions (from batch 1) 
Initially, SUPLEXA will be administered at Day 1 (baseline), Week 1 and Week 2 (Section 1.2, 
Figure 2). Subjects will be monitored closely at the clinic after each of these 3 weekly infusions 
with follow-up phone calls as described below. 
The first 3 subjects in each cohort will be enroled and subsequently dosed in a staggered manner, 
at least 1 week apart to allow for evaluation of safety. These subjects will be monitored for safety 

 
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in the clinic for 6 hours after each of the 3 weekly infusions and be contacted by phone on a daily 
basis (weekdays) between these weekly infusions for up to 5 days post final treatment. While the 
Investigator will review safety data on a continual basis, the DSMB will have an opportunity to 
review the first 3 subjects in each cohort who receive at least 3 doses of SUPLEXA to further 
evaluate safety and make a recommendation to the Sponsor concerning continuation or 
enrolment, pause in enrolment or study termination.  
While the DSMB reviews the data from the first 3 subjects in each cohort, additional subjects 
will be screened and enroled into each cohort. These additional subjects will not be dosed until 
the first 3 subjects in their cohort are cleared by the DSMB. The dosed subjects in Protocol 
Amendment #2 and #3 will be monitored closely at the clinic for at least 3 hours after each of the 
3 weekly infusions with follow-up phone calls every 2 business days between treatments and for 
up to 5 days post the 3rd infusion. If any of these subjects experience an adverse event of Grade 
3 or greater, the longer in-clinic monitoring window of 6 hours post each of the first 3 weekly 
infusions and daily calls will be reimplemented as done for the first 3 subjects. During the 
observation period post SUPLEXA administration, subjects will be monitored for any AEs and 
immediate post infusion reaction(s) every 90 minutes. 
The first subjects in Amendment #2 and #3 were enroled and treated, and evaluated for DLTs, 1 
week after the 1st dose and 2nd dose (prior to administration of 2nd dose and 3rd dose, 
respectively). The DLT criteria and DLT assessment period(s) are defined in Section 6.5.  
• Subsequent weekly infusions (after dose 3 with SUPLEXA batch 1 and batch 2)  
After completion of the first 3 weekly SUPLEXA batch 1 infusions, based on emerging data 
from prior subjects, disease evaluation (as described below), the discretion of the Investigator, 
and in agreement with the subject, treating physician and the Sponsor’s Medical Monitor (or 
designee), the treatment period of SUPLEXA may be extended as follows:  
Subjects will continue to receive SUPLEXA treatments of approximately 5 B cells, every 2 
weeks with a wider window -1 day to +7 days until either, a) depletion of SUPLEXA batch 1 
doses *, or b) disease progression is assessed by the Investigator per  iRECIST v1.1, or c) 
unacceptable toxicity, or other reasons for discontinuation as described in Section 7.2.   
The 5 B cells will be provided as two bags of SUPLEXA targeted at 2.5B cells until all product 
used, unless there is only a single dose unit left, upon which time the subject may receive a 
single bag until more SUPLEXA is manufactured for them. 
An additional SUPLEXA batch #2 may be manufactured for a subject based on (a) last dose of 
batch 1 and the investigator and subject and sponsor agree, then prior to the administration of the 
last SUPLEXA dose, blood can be drawn for SUPLEXA manufacturing of batch 2; or (b) > 2 
weeks and < 8 weeks after the last dose of SUPLEXA administered, blood is collected for batch 
2. 
Note that subjects enroled in SUPLEXA-101,Version 3.0 or 2.0, and had SUPLEXA 
manufacturing started on or before October 31, 2022, may logistically be unable to have the 
consecutive administration of the recommended dosing regimen. These patients are therefore 
exempt from the defined gap in dosing, and the sequential dosing regimen described above. 
However, upon possible restarting additional doses of SUPLEXA, the dosing must be sequential 
until either, a) depletion of SUPLEXA batch 1 doses *, or b) disease progression is assessed by 

 
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the Investigator per  iRECIST v1.1, or c) unacceptable toxicity, or other reasons for 
discontinuation as described in Section 7.2.   
Subjects will be monitored at the clinic for at least 90 minutes (+/- 30 min) after each infusion 
for AE and ISR. 
To account for the well-recognized phenomenon of tumor pseudo-progression or delayed 
response with immunotherapies, subjects may continue to receive SUPLEXA beyond RECIST 
v1.1 defined progression at the discretion of the Investigator. To confirm disease progression 
according to iRECIST, pseudo-progression will be further assessed at the next tumor assessment 
imaging time point after 4 weeks later but not exceeding 8 weeks from the date of initial 
documentation of suspected disease progression, and provided no other drug related adverse 
event occur warranting immediate cessation for clinical reasons. Otherwise, patients will 
continue to be dosed until all doses are used or progression is confirmed, whichever comes first. 
*For each subject treatment duration will be variable and will depend on SUPLEXA 
manufacturing yield. It is anticipated that batch 1 (manufactured during screening)  may be 
sufficient for up to 15 individual 2.5M SUPLEXA doses. In this regimen that would mean 3 
doses as once a week dose, thereafter 3 doses at 2-week intervals, and one dose at the two-week 
interval to exhaust all product made. When batch 1 is depleted, batch 2 will be prepared (as 
described above during screening). During batch 2 manufacturing period, there may be a gap of 
up to 60 days in dosing. 
Decision for treatment extension will be based on: 
• Subject’s overall safety status including AE rate, clinically significant findings from 
safety laboratory (including parameters indicative of TLS, e.g., uric acid elevation), 
physical examination, vital signs; or 
• Subject deriving clinical benefit from treatment with SUPLEXA based on RECIST 
v1.1 and iRECIST for solid tumours and laboratory parameters for haematological 
malignancies; Subjects who are already enroled and received at least 3 weekly doses, 
treatment extension will be based on their latest radiographic scan / laboratory 
evaluation; or 
• Exploratory outcomes (pharmacodynamics and correlative biomarkers), if available 
for review. 
Disease Evaluation 
For subjects in the solid tumours cohort, the on-treatment radiographic assessments of chest, 
abdomen, and pelvis will be performed per standard of care intervals throughout the course of 
the study. The first radiographic scan after receiving SUPLEXA will be performed at Week 6-12 
weeks after the 1st SUPLEXA infusion and thereafter every 6-12 weeks depending on tumour 
type and as clinically indicated per investigator’s discretion. 
These scans should be available for assessment by the Sponsor, if requested. The response 
evaluation will be assessed by the Investigator according to RECIST v1.1 and iRECIST until 
unequivocal radiographic disease progression, or until the subject starts a subsequent anticancer 
therapy (whichever comes first). The tumour assessment (imaging) for confirmation of response 
should be performed no less than 4 weeks after the criteria for response are first met. All 

 
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radiographic scans will be collected and held for possible future retrospective evaluation by 
BICR. 
For subjects in the haematological malignancies cohort, disease evaluation will be conducted 
every 4 weeks, as clinically indicated throughout the study. 
Follow-up – All Subjects 
All subjects will be followed up every 8 weeks for 48 weeks post last dose of study intervention 
for PFS and OS; visits are in-clinic unless patient is being followed for survival status only. The 
end of study (EOS) or early termination (ET) visits must be done in person within 30days of 
decision for ET or EOS. Beyond 48 weeks post last dose of study intervention, subjects may be 
contacted for survival status, disease status and initiation of subsequent anticancer therapies 
every 12 weeks up to a maximum of 24 months after the last dose of study intervention or earlier 
if the study is terminated by the Sponsor. 
Subjects who permanently discontinue study intervention early will be encouraged to remain in 
the study (refer to Section 7.2). Subjects who begin new anti-cancer therapy will be permanently 
withdrawn from the study with no further long-term follow up. 
Subjects who withdraw early from the study may be followed-up via phone or in person every 12 
weeks at a minimum or sooner as required by the Investigator to determine OS and PFS until 
they begin new anti-cancer therapy. 
Number of Subjects 
Up to 60 subjects may be enroled with a cap of about 8 subjects per individual tumour type with 
a prioritization and focus on melanoma, breast, prostate, lung, and haematological malignancies. 
If promising anti-tumour activity coupled with acceptable safety is observed, overall sample size 
and/or cap per tumour type may be expanded. 
Study Duration 
For each subject, the study duration is expected to be as follows: 
Screening:  
Up to 5 weeks. 
Treatment: 
Minimally 3 weeks for subjects starting at recommended 
dose. 
Optional additional doses will be at discretion of the 
investigator in agreement with Sponsor. Subjects may 
receive additional treatment with study intervention 
depending on emerging data and SUPLEXA manufacturing 
yield. If 2 batches of SUPLEXA with optimal 15 units, this 
could be up to 24 weeks. 
Follow-up: 
Every 8 weeks for up to 48 weeks from last dose of study 
intervention or earlier if the study is terminated by the 
Sponsor.  
Beyond Week 48, subjects may be contacted every 12 
weeks up to a maximum of 24 months after the last dose of 

 
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SUPLEXA or earlier if the study is terminated by the 
Sponsor. 
 
Data Safety Monitoring Committee  
A Data Safety Monitoring Committee (DSMB) will be composed of at least 3 external members 
and include experts in the field of oncology and clinical studies, or biostatistics will regularly 
monitor overall safety, as well as general aspects of study conduct, to ensure that the benefits and 
risks of study participation remain acceptable. The DSMB will make recommendations to the 
Sponsor regarding any modifications to the study. Refer to Section 9.3.6. 

 
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1.2 
SCHEMA  
Figure 1: Study Schema – Screening and Manufacturing Period (Day -35 to Day 1) in All Subjects 
 
 
Treatment period is minimally 3 doses one week apart 
Abbreviations: IV= intravenous; Liq N2= liquid nitrogen; QA = quality assurance; QC = quality control 
 

 
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Figure 2: Study Schema – Overview (minimally 3 doses) 
 
Abbreviations: DLT= dose limiting toxicities; EOS = end of study 
 

 
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1.3 
SCHEDULE OF ACTIVITIES  
Study period 
Screening 
Treatment Period  
(Weekly dosing) 
TREATMENT GAP 
Treatment 
Extension 
Period 
Follow Up 
after last 
dose 
 
Notes 
End of Study (EOS) will be conducted within 30d for all 
subjects who completed the study per protocol;  
Early termination (ET) visit will be conducted within 30d 
or subjects who withdraw from the study prematurely. 
1. Continued dosing per discretion of the investigator 
until depletion of manufactured SUPLEXA batch or 
confirmed disease progression by RECIST v1.1 or 
iRECIST, or withdrawal of consent by subject, 
whichever occurs first. 
SUPLEXA Batch 1 
Batch 2  
Study Treatment 
Week 
-5 
-5 
to  
-1 
First 3 infusions  
Additional 
doses 1  
Doses 1  
 
 
 
Week 0 
Day 1/ 
Baseline 
1, 2 
 
 
Every 8 
weeks up to 
48 weeks 
from last 
dose 
EOS/ 
ET 
Visit Window (days) 
 
±2 
 
±2 
-1 to +7 
60  
-1 to +7 
±5 
 
±28 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Demographic and 
medical history 
Xa 
 
 
 
 
 
 
 
 
 
a. Medical history of the prior 3 years including any 
co-morbid conditions requiring active treatment and 
significant surgeries.  
Inclusion/Exclusion 
X 
X 
 
 
 
 
 
 
 
 
 
Solid 
tumour/haematologic 
malignancy 
diagnosis 
confirmation and 
disease staging 
Xb 
 
 
 
 
 
 
 
 
 
b. Radiology reports and photography images from 
imaging that occurred within 4 weeks of signing 
informed consent and throughout the study should 
also be noted as available for later access by 
Sponsor (if required). 
History of prior anti-
cancer therapy 
 
Xc 
 
 
 
 
 
 
 
 
c. Information on all interventions (systemic 
therapy, surgery, radiation treatment) related to the 
subject’s cancer will also be collected. Prior 
immunotherapy dosing concentration and cycle 
numbers should be captured.  
Prior & concomitant 
medications  
 
X 
X 
X 
X 
 
X 
X 
X X 
 

 
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Study period 
Screening 
Treatment Period  
(Weekly dosing) 
TREATMENT GAP 
Treatment 
Extension 
Period 
Follow Up 
after last 
dose 
 
Notes 
End of Study (EOS) will be conducted within 30d for all 
subjects who completed the study per protocol;  
Early termination (ET) visit will be conducted within 30d 
or subjects who withdraw from the study prematurely. 
1. Continued dosing per discretion of the investigator 
until depletion of manufactured SUPLEXA batch or 
confirmed disease progression by RECIST v1.1 or 
iRECIST, or withdrawal of consent by subject, 
whichever occurs first. 
SUPLEXA Batch 1 
Batch 2  
Study Treatment 
Week 
-5 
-5 
to  
-1 
First 3 infusions  
Additional 
doses 1  
Doses 1  
 
 
 
Week 0 
Day 1/ 
Baseline 
1, 2 
 
 
Every 8 
weeks up to 
48 weeks 
from last 
dose 
EOS/ 
ET 
Visit Window (days) 
 
±2 
 
±2 
-1 to +7 
60  
-1 to +7 
±5 
 
±28 
Survival status and 
subsequent 
anticancer therapy 
 
 
 
 
 
 
 
 
Xd Xd 
d. Beyond Week 48, subjects enrolled in the trial 
may be contacted every 12 weeks up to a maximum 
of 24 months after the last dose of SUPLEXA or 
earlier if the study is terminated by the Sponsor. 
Physical exam and 
heighte  
X 
 
X 
Xf 
Xf 
 
Xf 
X 
 
X 
e. Height at screening only 
f. Symptom-directed physical exam 
Vital signs and weight
X 
 
X 
X 
X 
 
X 
X 
 
X 
 
Performance status  
X 
 
X 
X 
X 
 
X 
X 
 
X 
Eastern Cooperative Oncology Group (ECOG) for 
solid tumours; Karnofsky for haematologic 
malignancies. 
Electrocardiogram 
(ECG) 
 
X 
X 
Xg 
Xg 
 
Xg 
 
 
X 
g. As clinically indicated 
Disease evaluation 
by Response 
Evaluation Criteria 
in Solid Tumours 
(RECIST) v1.1 and 
immune RECIST 
(iRECIST) (solid 
tumours only) 
 
Xh 
 
 
Xi 
 
Xi 
Xi 
 
Xi 
h. Scans within 4 weeks of screening will be 
accepted. 
i. Using standard of care scan schedule for the 
specified solid tumour. The first radiographic scan 
after receiving SUPLEXA will be performed at 
Week 6-12 weeks after the 1st SUPLEXA infusion 
and thereafter every 6-12 weeks depending on 
tumour type and as clinically indicated per 
investigator’s discretion. 
 

 
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Study period 
Screening 
Treatment Period  
(Weekly dosing) 
TREATMENT GAP 
Treatment 
Extension 
Period 
Follow Up 
after last 
dose 
 
Notes 
End of Study (EOS) will be conducted within 30d for all 
subjects who completed the study per protocol;  
Early termination (ET) visit will be conducted within 30d 
or subjects who withdraw from the study prematurely. 
1. Continued dosing per discretion of the investigator 
until depletion of manufactured SUPLEXA batch or 
confirmed disease progression by RECIST v1.1 or 
iRECIST, or withdrawal of consent by subject, 
whichever occurs first. 
SUPLEXA Batch 1 
Batch 2  
Study Treatment 
Week 
-5 
-5 
to  
-1 
First 3 infusions  
Additional 
doses 1  
Doses 1  
 
 
 
Week 0 
Day 1/ 
Baseline 
1, 2 
 
 
Every 8 
weeks up to 
48 weeks 
from last 
dose 
EOS/ 
ET 
Visit Window (days) 
 
±2 
 
±2 
-1 to +7 
60  
-1 to +7 
±5 
 
±28 
Assessment by RECIST v1.1 and iRECIST will be 
done before the first dose of study intervention until 
end of study (EOS visit). Scans and photography 
will be assessed locally by the Investigator. Lesions 
will be numbered identically for each visit as Target 
and Non-target, New lesions. 
Disease evaluation 
for haematologic 
malignancies only 
 
X 
 
 
X* 
 
X* 
X* 
 
X 
*As clinically indicated, may also be conducted 
every 4 weeks, starting 4 weeks after the 3rd dose 
Complete blood 
count (CBC) with 
differential and 
blood chemistry 
X 
 
Xj 
X j, k 
X j 
 
X j 
X 
 
X 
Refer to Table 5 for list of parameters to be 
evaluated 
j. Predose 
k. Repeat at baseline in local hospital lab for stat 
results, and central lab sample to be shipped 
Collect blood for 
pharmacodynamic 
immune 
assessments, 
including cytokines 
 
 
X 
X 
X 
 
X 
Xl 
 
 
Refer to Section 8.4 for list of parameters to be 
evaluated 
l. collected where possible post dose 

 
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Study period 
Screening 
Treatment Period  
(Weekly dosing) 
TREATMENT GAP 
Treatment 
Extension 
Period 
Follow Up 
after last 
dose 
 
Notes 
End of Study (EOS) will be conducted within 30d for all 
subjects who completed the study per protocol;  
Early termination (ET) visit will be conducted within 30d 
or subjects who withdraw from the study prematurely. 
1. Continued dosing per discretion of the investigator 
until depletion of manufactured SUPLEXA batch or 
confirmed disease progression by RECIST v1.1 or 
iRECIST, or withdrawal of consent by subject, 
whichever occurs first. 
SUPLEXA Batch 1 
Batch 2  
Study Treatment 
Week 
-5 
-5 
to  
-1 
First 3 infusions  
Additional 
doses 1  
Doses 1  
 
 
 
Week 0 
Day 1/ 
Baseline 
1, 2 
 
 
Every 8 
weeks up to 
48 weeks 
from last 
dose 
EOS/ 
ET 
Visit Window (days) 
 
±2 
 
±2 
-1 to +7 
60  
-1 to +7 
±5 
 
±28 
Serology  
 
Xm 
 
 
 
 
 
 
 
 
Refer to Table 5 for list of parameters to be 
evaluated 
m. HIV positivity is disqualifying as this might be 
amplified in ex vivo stimulation 
Syphilis screening 
test 
 
X 
 
 
 
 
 
 
 
 
 
Pregnancy test 
(WOCBP only) 
 
X 
 
 
 
 
 
 
 
X 
Women of childbearing potential (WOCBP) 
Negative test must be performed within 72 hours 
prior to first study intervention 
Urinalysis 
 
X 
Xn  
 
Xn  
 
 
X 
Refer to Table 5 for list of parameters to be 
evaluated 
n. As clinically indicated; urinalysis to include 
dipstick and microscopic examinations when 
findings are abnormal 
Blood sample for 
SUPLEXA 
manufacturing 
Xo 
 
 
 
 
Xp 
 
 
 
 
o. Batch 1: Subjects who will have adequate 
evidence of blast formation at the manufacturing 
facility (notification of yield will be 5 days after the 
blood collection), will proceed to next Screening 

 
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Study period 
Screening 
Treatment Period  
(Weekly dosing) 
TREATMENT GAP 
Treatment 
Extension 
Period 
Follow Up 
after last 
dose 
 
Notes 
End of Study (EOS) will be conducted within 30d for all 
subjects who completed the study per protocol;  
Early termination (ET) visit will be conducted within 30d 
or subjects who withdraw from the study prematurely. 
1. Continued dosing per discretion of the investigator 
until depletion of manufactured SUPLEXA batch or 
confirmed disease progression by RECIST v1.1 or 
iRECIST, or withdrawal of consent by subject, 
whichever occurs first. 
SUPLEXA Batch 1 
Batch 2  
Study Treatment 
Week 
-5 
-5 
to  
-1 
First 3 infusions  
Additional 
doses 1  
Doses 1  
 
 
 
Week 0 
Day 1/ 
Baseline 
1, 2 
 
 
Every 8 
weeks up to 
48 weeks 
from last 
dose 
EOS/ 
ET 
Visit Window (days) 
 
±2 
 
±2 
-1 to +7 
60  
-1 to +7 
±5 
 
±28 
visit. Subjects with insufficient yields will be 
considered screen failures and will be replaced. 
 
p. Batch 2: After completion of Batch 1 and if 
subjects are eligible to continue to receive 
SUPLEXA, batch number 2 manufacturing and 
processing will take place. 
 
Pre-treatment 
prophylaxis  
 
 
X 
X 
X 
 
X 
 
 
 
The following pretreatment regimen is suggested, 
although a different regimen based on local standard 
of care/institutional practices is permitted: 
Administer acetaminophen 1000 mg (PO) for 
potential fever, diphenhydramine 12.5 mg PO (for 
potential rash) and allopurinol (100 mg) IV or PO 
for potential TLS in subjects who are at intermediate 
risk for TLS approximately 1 hour (60 min ± 
20 min) before SUPLEXA infusion,  Refer to 
Section 6.8.1 and 10.8Section 10.8 for further 
details. 
SUPLEXA 
administration IV 
 
 
Xq 
Xq 
Xr 
 
Xr 
 
 
 
q. Weekly 2.5 billion cells  
r. Additional treatment every 2 weeks at 5.0 B cells 
will be the investigator’s assessment and in 

 
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Study period 
Screening 
Treatment Period  
(Weekly dosing) 
TREATMENT GAP 
Treatment 
Extension 
Period 
Follow Up 
after last 
dose 
 
Notes 
End of Study (EOS) will be conducted within 30d for all 
subjects who completed the study per protocol;  
Early termination (ET) visit will be conducted within 30d 
or subjects who withdraw from the study prematurely. 
1. Continued dosing per discretion of the investigator 
until depletion of manufactured SUPLEXA batch or 
confirmed disease progression by RECIST v1.1 or 
iRECIST, or withdrawal of consent by subject, 
whichever occurs first. 
SUPLEXA Batch 1 
Batch 2  
Study Treatment 
Week 
-5 
-5 
to  
-1 
First 3 infusions  
Additional 
doses 1  
Doses 1  
 
 
 
Week 0 
Day 1/ 
Baseline 
1, 2 
 
 
Every 8 
weeks up to 
48 weeks 
from last 
dose 
EOS/ 
ET 
Visit Window (days) 
 
±2 
 
±2 
-1 to +7 
60  
-1 to +7 
±5 
 
±28 
consultation with Sponsor’ Medical Monitor. 
Cumulative dose depends on the individual subject 
SUPLEXA manufacturing yield in batch 1 and in 
batch 2. 
Dose limiting 
toxicity (DLT) 
assessment 
 
 
DLT assessment 
period  
 
 
 
Refer to Section 6.5 for DLT criteria. 
DLT assessment periods: 
Period 1: 1 week after the 1st dose (before 2nd dose 
administration) 
Period 2: 1 week after 2nd dose (before 2nd 3rd 
dose administration) 
1 
2 
 
 

 
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Study period 
Screening 
Treatment Period  
(Weekly dosing) 
TREATMENT GAP 
Treatment 
Extension 
Period 
Follow Up 
after last 
dose 
 
Notes 
End of Study (EOS) will be conducted within 30d for all 
subjects who completed the study per protocol;  
Early termination (ET) visit will be conducted within 30d 
or subjects who withdraw from the study prematurely. 
1. Continued dosing per discretion of the investigator 
until depletion of manufactured SUPLEXA batch or 
confirmed disease progression by RECIST v1.1 or 
iRECIST, or withdrawal of consent by subject, 
whichever occurs first. 
SUPLEXA Batch 1 
Batch 2  
Study Treatment 
Week 
-5 
-5 
to  
-1 
First 3 infusions  
Additional 
doses 1  
Doses 1  
 
 
 
Week 0 
Day 1/ 
Baseline 
1, 2 
 
 
Every 8 
weeks up to 
48 weeks 
from last 
dose 
EOS/ 
ET 
Visit Window (days) 
 
±2 
 
±2 
-1 to +7 
60  
-1 to +7 
±5 
 
±28 
AE assessment 
X 
X 
Xs 
Xs 
Xs 
 
X 
X 
 
Xt 
s. The first 3 subjects in each cohort will be 
monitored closely at the clinic for at least 6 hours 
after each of the first 3 weekly infusion and be 
contacted by phone on a daily basis (weekdays) 
between these weekly infusions for up to 5 days post 
the 3rd treatment. 
During the observation period (as specified above), 
all subjects will be monitored for post infusion 
reaction(s) and AEs every 90 minutes. 
 
Subsequent subjects will be monitored for 90 min 
post dose for post infusion reaction(s) and AEs. 
 
If any of these subjects experience an adverse event 
of Grade 3 or greater, the longer in-clinic monitoring 
window of 6 hours post each of the first 3 weekly 

 
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Study period 
Screening 
Treatment Period  
(Weekly dosing) 
TREATMENT GAP 
Treatment 
Extension 
Period 
Follow Up 
after last 
dose 
 
Notes 
End of Study (EOS) will be conducted within 30d for all 
subjects who completed the study per protocol;  
Early termination (ET) visit will be conducted within 30d 
or subjects who withdraw from the study prematurely. 
1. Continued dosing per discretion of the investigator 
until depletion of manufactured SUPLEXA batch or 
confirmed disease progression by RECIST v1.1 or 
iRECIST, or withdrawal of consent by subject, 
whichever occurs first. 
SUPLEXA Batch 1 
Batch 2  
Study Treatment 
Week 
-5 
-5 
to  
-1 
First 3 infusions  
Additional 
doses 1  
Doses 1  
 
 
 
Week 0 
Day 1/ 
Baseline 
1, 2 
 
 
Every 8 
weeks up to 
48 weeks 
from last 
dose 
EOS/ 
ET 
Visit Window (days) 
 
±2 
 
±2 
-1 to +7 
60  
-1 to +7 
±5 
 
±28 
infusions and daily calls will be reimplemented as 
done for the first 3 subjects. 
 
t. For subjects with unresolved treatment-related 
toxicity at last dosing visit, follow as medically 
appropriate until stabilization. 
 
Only SAEs that are believed related to study 
intervention will collected. 

 
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2 
INTRODUCTION 
2.1 
STUDY RATIONALE 
This Phase 1, first-in human (FIH), open-label study is designed to assess the safety, tolerability, 
and preliminary clinical efficacy of repeated intravenous (IV) infusion of SUPLEXA therapeutic 
cells (referred to as SUPLEXA throughout this protocol) monotherapy in subjects with 
measurable metastatic solid tumours and haematologic malignancies. 
SUPLEXA is manufactured using an ex vivo procedure that employs proprietary ENgineered 
Leukocyte STimulator (ENLIST™) cells (Figure 3). ENLIST cells are derived from a standard 
melanoma cell line (SK-MEL-2) sourced from the National Institute of Health (NIH) and have 
been genetically engineered to express an array of immunomodulatory ligands. 
Figure 3: SUPLEXA Manufacturing Overview 
 
Abbreviations: Allo-HLA, allogeneic human leukocyte antigen; ENLIST, ENgineered Leukocyte STimulator. 
The ENLIST Induction Reagent (IR) are designed to specifically engage and activate multiple 
subsets of naïve resting peripheral blood mononuclear cells (PBMC) through their naturally 
expressed cell surface receptors. Once activated, these immune cell subsets are capable of 
secondary interactions which further augment their activation state. 
The ENLIST cells are subjected to multiple cycles of freeze-thaw prior to coincubation with 
PBMC, to render them incapable of replication and thus eliminating the possibility that living 
tumour cells enter the manufacturing reaction. The overall manufacturing process requires 
minimal manipulation during the PBMC-ENLIST co-incubation period, resulting in a 
heterogenous, autologous, non-genetically engineered cell mixture that comprises SUPLEXA. 
SUPLEXA therapeutic cells differ from their naïve, untreated, resting PBMC precursors profiles 
with respect to their composition, phenotype, and function, observed after incubation with 

 
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ENLIST. This is evident by their enhanced proliferation state and enhanced cytokine production 
profile. They are predominantly comprised of natural killer (NK) and T cell receptor 
(TCR)-gamma/delta ()-positive T cells of cytotoxic CD8-positive and CD4-positive T 
lymphocytes (CTL). Note, all cells described are known to individually possess some anti-
tumour activity. Remarkably, this mixed cell population has the ability to rapidly lyse a variety 
of tumour lines at exceedingly low effector-to-target cell ratios in an in vitro functional cytolysis 
assay. Moreover, flow sort data reveal that the cytolytic activity resides in both the CD56-
positive (NK cell population) and CD56-negative populations, indicating that multiple sub-
populations of SUPLEXA are independently capable of lysing tumour. SUPLEXA represents an 
autologous, multifaceted, tumour killing strategy requiring no further sub-fractionation to display 
activity. 
Furthermore, SUPLEXA has been demonstrated to show anti-tumour activity on all tumour cell 
lines tested to date irrespective of origin (e.g., melanoma, colorectal, breast, prostate, leukemia, 
glioma, ovarian, renal, glioma, and leukemia), while simultaneously showing no impact on 
allogeneic or autologous naïve normal PBMC. 
Nonclinical studies have shown that a single, sub optimal IV dose of 3 million cells of 
SUPLEXA in a mouse xenograft model yielded statistically significant anti-tumour activity with 
no apparent safety signals. A trend toward tumour growth inhibition was observed between 
treated and untreated animals as early as about 10 days following administration and achieved 
statistical significance within 3 weeks. No safety signals were observed in the animal followed 
for 40 days and a highly statistically significant difference in average tumour size was observed 
at about 3 weeks (p<0.05) which improved through 5 weeks (p<0.005). 
In the LU5200 subcutaneous non-small cell lung cancer patient derived xenografts (PDX) model, 
multiple SUPLEXA doses of 20 million cells administered weekly for 3 weeks. Treatment 
resulted in statistically significant tumour growth inhibition that was apparent at approximately 
1-2 weeks following first dose. Repeated dosing did not show any adverse health effects in the 
mice. SUPLEXA was thus deemed safe and well tolerated. 
2.2 
BACKGROUND 
The therapeutic landscape for many metastatic cancers has recently been transformed by the 
approval of molecular targeted agents and immunotherapy including immune checkpoint 
inhibitors (e.g. monoclonal antibodies (mAbs) against cytotoxic T-lymphocyte-associated protein 
4 (CTLA-4), and programmed death-1 (PD-1)), bispecific biologics and chimeric antigen 
receptor (CAR)-cellular therapies (Kruger, 2019; Liu, 2019). The field of immunotherapy is 
currently expanding in hopes of offering durable anti-tumour immune responses for patients with 
advanced solid tumours and haematologic malignancies. Arguably one of the most comparable, 
yet distinct approaches to SUPLEXA cells is tumour infiltrating lymphocytes (TIL) therapy 
being advanced by Iovance. Like Alloplex, Iovance starts with primary autologous immune cells 
from a patient, requiring a resected tumour, followed by ex vivo activation/expansion and finally 
administration back to the patient. The approaches, however, are quite distinct in that the cells 
adoptively transferred to the patient by Iovance are predominantly tumour reactive CD8-positive 
cells while those comprising SUPLEXA have a more heterogeneous phenotype. Manufacturing, 
which is integral to any cellular therapy-is also vastly different. Iovance has to contend with 
variable efficiency of TIL isolation; employing feeder cells to expand the TILs ex vivo, and then 
providing evidence to regulators that neither feeder cells nor residual tumour cells are in the final 

 
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product. In contrast, SUPLEXA manufacturing begins with a standard blood draw and undergoes 
a simple and robust ex vivo expansion that yields low interpatient variability and provides for 
multiple dosing. 
2.2.1 
Study Intervention Overview 
Alloplex is developing SUPLEXA as a multicellular adoptive immunotherapy for solid tumours 
and haematologic malignancies. SUPLEXA is not engineered but minimally manipulated ex vivo 
to enhance their anti-tumour activity. SUPLEXA is derived by stimulation of naturally occurring 
receptors on the PBMC with physiologic membrane expressed immunomodulatory ligands 
expressed in the ENLIST cells. SUPLEXA being a non-engineered product presumably retains 
all the homeostatic mechanism typical of normal immune cells. As SUPLEXA acquire the ability 
to kill tumour types in the ex vivo manufacturing process, they recognize the stimulatory 
ENLIST cells as tumour derived and eliminate any living in the co-culture manufacturing 
procedure (Figure 4). As ENLIST cells in the final protocol have already been rendered non-
viable by repeated cycles of freeze-thaw, this latter observation is not relevant to the clinical 
study. 
Figure 4: SUPLEXA Mechanism of Action Overview 
 
When the SUPLEXA cells are harvested they contain no detectable ENLIST cells, avoiding 
subject exposure to tumour-derived cells. SUPLEXA is thus a differentiated cellular mixture of 
the patient’s own PBMC’s which are predominantly comprised of natural killer (NK), T cell 
receptor (TCR)-gamma/delta () positive T cells, CD8-positive and CD4-positive cells. 
NK cells are considered as the most effective immune cell subpopulation to monitor and to clear 
diseased cells in vivo. They can recognize and kill abnormal cells that lack major 
histocompatibility complex (MHC) restriction or prior sensitization (Vivier, 2008). Different 
from other lymphocytes, NK cell recognition is not controlled by antigen specificity but 
integration of signals from activating and inhibitory receptors recruited by ligands expressed on 
putative target cells. Adoptive transfer of NK cells with high yields and high quality is a direct 
and fundamental approach to replacing, restoring and improving the function of the immune 
system (Hu, 2019; Oh, 2019). 
γδ T cells have unique capabilities to recognize transformed cells and kill, or to regulate the 
immune response against them (Simoes, 2018). These cells have remarkable flexibility 
employing their TCR and/or NK cell receptors for target cell recognition and their activation is 

 
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typically independent of antigen presentation by MHC molecules. Furthermore, NK cell 
receptors on the surface of γδ T cells allow for very fast responses against transformed cells, thus 
contributing to a first line of defence that precedes antigen-specific αβ T-cell responses (Carding, 
2002; De Rosa, 2004; Ribeiro, 2015). Therefore, γδ T cells have the potential to overcome 
problems in cancer therapy especially for tumours lacking tumour-specific antigens for targeting 
by antibodies or CAR T cells, or unresponsive to immune checkpoint inhibitors (Pauza, 2018). 
CD8-positive T cells and CD4-positive helper T cells are generated in the thymus and express 
the T-cell receptor. CD8-positive cytotoxic T cells express a dimeric co-receptor, usually 
composed of one CD8α and one CD8β chain, and recognize peptides presented by MHC Class I 
molecules, found on all nucleated cells. CD8-positive T cells are important for immune defence 
against intracellular pathogens, including viruses and bacteria, and for tumour surveillance. 
CD8-positive T cells have well understood anti-tumour mechanisms of action including secretion 
of cytokines, primarily tumour necrosis factor (TNF)-α and interferon (IFN)-γ, and the 
expression of cytolytic granules upon target recognition (Ostroumov, 2018). 
CD4-positive T cells are the major regulatory cells of the immune system, known to support B 
lymphocytes and help induce CD8-positive T‐cell responses by increasing antigen‐presenting 
and co‐stimulatory capacities of dendritic cells. CD4-positive T cells can directly recognize 
antigen on tumour cells, if these express MHC class II (Lai, 2011; Ahrends, 2018). There are 
however no regulatory T cells detected in SUPLEXA. 
SUPLEXA is intended for IV administration and is manufactured and packaged according to 
current Good Manufacturing Practice (cGMP) standards. SUPLEXA has been tested in non-
clinical in vitro functional cytolysis assay and in a single dose xenograft model in mouse, as well 
as a repeat dose study in PDX mouse model. A detailed description of the manufacturing 
process, quality control, release criteria, pharmacology, efficacy, and safety are provided in the 
Investigator’s Brochure (IB). 
2.3 
BENEFIT AND RISK ANALYSIS 
More detailed information about the known and expected risk-benefit ratio and reasonably 
expected adverse events attributable to SUPLEXA can be found in the IB. 
2.3.1 
Risk Assessment 
There are no identified or potential risks of particular severity anticipated based on toxicological 
data with SUPLEXA in animals, nor based on the mechanism of action and composition (an 
autologous population of NK and  T cells, CD8-positive and CD4-positive cells). Additionally, 
these cellular components have individually been evaluated in clinical studies and found to be 
well tolerated based on the lack of SAE (Section 2.2). 
SUPLEXA is a first-in-class non-engineered autologous cell therapy. This study is ongoing and 
as of Sept 19 2022,  more than 15 subjects were enroled in the study and received from 3 to 6 
doses of SUPLEXA. No treatment-related SAE or adverse events had been reported.  
Although nothing has been observed to date in blood chemistry, urinalysis, hematological or any 
labs, nor in any reported AE/SAE, potential risks based on the ongoing study and theoretical 
concerns that may be associated are presented below (Table 1) based on studies involving the 
autologous administration of CTL (Ohtani, 2014), CAR-T (Shivani, 2018) and dendritic cells 

 
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(Anguille, 2014) as well as the allogeneic administration of NK cells (Kyle B. Lupo, 2019), and 
 T cells (Pauza, 2018). 
Table 1: 
Potential Risks and Mitigation Strategy 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale 
for Risk 
Mitigation Strategy 
Possible Concern (not observed in nonclinical studies) 
Cytokine release syndrome 
(CRS) – low risk for SUPLEXA 
since cells have only received 
physiologic signals through 
native receptors and presumably 
retain all homeostatic 
mechanisms. 
Observed in CAR-T therapy 
owing to the supra-physiologic 
T-cell activation signal 
conferred by an engineered 
CAR protein. 
Cytokine storm as observed in 
CAR-T therapy is now well 
managed with a neutralizing 
anti-IL-6 mAb. 
Please refer Appendix 6, 
Section 10.7 for CRS toxicity 
treatment guidelines. 
Tumour Lysis Syndrome (TLS). 
Based on CAR-T therapy for 
hematologic malignancies, 
although TLS is less likely for 
solid tumor. 
When TLS is observed, it may 
be considered a positive signal 
for synchronous tumour killing 
by the study intervention 
employed. 
Subjects will be followed 
closely throughout the study for 
signs and symptoms of 
hypersensitivity and treated per 
institution guidelines as needed 
per the TLS toxicity 
management guidelines as noted 
in Appendix 7, Section 10.8,  
Preconditioning with 
Allopurinol can ameliorate the 
impact of high uric acid levels 
derived from TLS. 
Infection - low risk since 
endogenous immune system is 
not altered. 
Infection risk does not appear 
increased with various published 
adoptive immune cell therapies. 
Ensure sterile product through 
cGMP procedures. 
Neurologic events – low risk. 
 
CAR-T studies report some 
neuro risk possibly owing to 
presence of CAR defined 
antigen in the brain. 
Avoid subjects with brain 
disease to avoid confounding 
symptoms. 
Flu-like symptoms and fever – 
medium risk owing to immune 
activity of adoptively transferred 
cells. 
Note in multiple clinical studies 
but not rate limiting. 
As a sign of activity, flu-like 
symptoms should be monitored 
and preconditioning with 
Tylenol can mitigate the 
severity. 
Study Procedure 
Injection site reactions (redness, 
swelling, itching and 
tenderness). 
As with any infusion procedure, 
injection site reaction is 
possible. 
IV infusion will be done by 
trained personnel. 

 
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2.3.2 
Benefit Assessment 
As this is the FIH evaluation of SUPLEXA as a monotherapy, any estimate of efficacy in 
humans is based entirely on hypotheses developed from non-clinical data and other cellular 
therapies comprising the SUPLEXA components previously tested in the clinic. 
Nonclinical data with SUPLEXA provides a strong rationale for evaluating the potential clinical 
benefits in subjects with solid tumours and haematologic malignancies for whom available 
standard of care is not providing an adequate durable response as defined by complete (CR) or 
partial response (PR). It is anticipated that treatment with SUPLEXA may have a positive impact 
in subjects with advanced solid tumours and haematologic malignancies. 
2.3.3 
Overall Benefit: Risk Conclusion 
Overall, the SUPLEXA risk-benefit profile is considered favourable in the specific subject 
population being recruited into this FIH study.  
 
 

 
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3 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints 
Primary 
 
• To assess safety and tolerability of 
SUPLEXA in subjects with malignant 
solid tumour and haematologic 
malignancies. 
• Incidence of dose limiting toxicities (DLTs) (as 
described in Section 6.5.1. 
• Incidence of adverse events (AEs), and serious 
adverse events (SAEs) overall, by severity, by 
relationship to each study intervention, and 
those that led to discontinuation of study 
intervention. 
Secondary 
 
• Solid tumours cohort: To assess the 
efficacy of SUPLEXA in subjects with 
malignant solid tumour as assessed by the 
Investigator based on response evaluation 
criteria in solid tumours (RECIST) v1.1 or 
by changes in tumour-derived blood 
biomarkers. 
• Objective response rate (ORR) defined as the 
proportion of subjects with best overall response 
(BOCR) of either a complete response (CR) or 
partial response (PR). 
• Time to Progression (TTP). 
• Haematologic malignancies cohort: To 
assess the efficacy of SUPLEXA in 
subjects with haematologic malignancies 
(multiple myeloma, lymphoma, and 
chronic lymphocytic leukemia). 
• Objective response rate as defined by standard 
of care. 
Exploratory 
 
• Exploratory efficacy outcomes 
• Duration of Response (DOR) 
• Time to Response (TTR) 
• Clinical Benefit Rate (CBR) defined as CR + 
PR + stable disease (SD). 
• Progression-free Survival (PFS). 
• Overall Survival (OS). 
• Solid tumours cohort: Change in plasma 
biomarkers. 
• Haematologic malignancies cohort: Response-
relationship with correlative biomarkers in 
blood and bone marrow including 
immunophenotyping of circulating PBMC 
and/or bone marrow, gene expression, 
mutational analysis. 

 
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Objectives 
Endpoints 
• To evaluate anti-tumor activity of 
SUPLEXA by based on modified 
RECIST v1.1 for immune based 
therapeutics (iRECIST) 
• iORR 
• iPFS 
• iDOR 
• iDCR 
• To evaluate changes in disease 
biomarkers following treatment with 
SUPLEXA from blood. 
• Change from baseline in the following 
pharmacodynamic assays, including but not 
limited to: 
− Whole blood immune cell phenotyping 
(e.g., PBMC count and composition and 
select flow cytometric analysis). 

 
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4 
STUDY DESIGN 
4.1 
OVERALL STUDY DESIGN 
This is a FIH Phase 1, non-comparative, open-label, basket-design study. The study will consist 
of 2 cohorts: 
• Solid tumours cohort: This cohort will include subjects with histologically or cytologically 
confirmed measurable solid tumours (e.g., various squamous cell carcinomas (skin, cervical, 
vaginal, esophogeal, lung), melanoma, prostate, and breast cancer), radiographically 
confirmed as Stage 2 to 4 cancer. Subjects must fulfill entry criteria and not be currently 
receiving or under the residual influence of immunosuppressive therapies. 
• Haematologic malignancies cohort: This cohort will include subjects with histologically or 
cytologically confirmed multiple myeloma, lymphoma, and chronic lymphocytic leukemia 
(collectively termed as haematologic malignancies for the purposes of this protocol). 
Subjects must fulfill entry criteria and have relapsed or refractory advanced malignancy for 
which no standard therapy exists. 
A Data Safety Monitoring Committee (DSMB) will provide oversight of the study and will 
monitor safety on a regular basis throughout the study to recommend to the Sponsor on any 
modification of the study. Refer to Section 9.3.6. 
The study will be comprised of 3 periods. Screening, Treatment and Follow-up. Throughout the 
study, subjects will be evaluated as specified in the Schedule of Activities (SoA) in Section 1.3. 
Study schema is provided in Figure 2. 
4.1.1 
Screening Period – All Subjects 
Prior to enroling in the study, and before performance of any procedures, potential subjects will 
attend a Screening session where they will be provided with full information concerning details 
of the study assessments and procedures. They will also be provided with a Participant 
Information Sheet and Informed Consent Form (PICF). Prior to being required to sign the 
consent form, subjects will be given time to review study information and ask questions. 
After signing the PICF, potential candidates will undergo screening procedures over 2 visits 
during a Screening period lasting up to 5 weeks (Section 1.2, Figure 1). During Screening 
Visit 1, blood will be drawn for safety laboratory assessment (~5 mL) and for processing and 
manufacturing of SUPLEXA batch 1 (~50 mL of whole blood) and for exploratory studies 
(~20 mL of whole blood). Subjects who meet the safety laboratory inclusion criteria and have 
adequate evidence of blast formation at the manufacturing facility (notification of status will 
require 5 days from the initiation of culture), will proceed to Screening Visit 2. Subjects in whom 
the SUPLEXA blast formation does not occur will be considered screen failures and be replaced. 
This is expected to be < 10% of subjects. 
Standard of care tests/procedures that were performed prior to signing the consent can be used as 
part of the screening assessments if the procedures meet the protocol-required timelines (i.e., 
within 5 weeks of consent) and it is documented in the source documents that these procedures 
performed prior to signing the consent were standard of care procedures. 

 
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Eligibility criteria for study entry will be assessed locally by the Investigator; for the solid 
tumour cohort, screening radiographic scans (within 5 weeks of consent) will be collected and 
held for possible future retrospective evaluation by Sponsor or blinded independent central 
review (BICR). Safety laboratory assessments of all subjects will be rechecked for eligibility on 
the day of the first treatment with the local hospital laboratory (and the central laboratory for 
documentation), prior to dose with study intervention. 
4.1.2 
Treatment Period 
All eligible subjects will receive minimally 3 weekly dosing of SUPLEXA (target of 2.5 billion 
cells, a  range of  cells per 1.9 to 3.1 billion cells per dose, unless delayed due to DLTs; refer to 
Section 6.5.1). Thereafter additional doses may be available. 
Dosing will be done as follows: 
4.1.2.1 
First 3 SUPLEXA infusions (from batch 1) 
Initially, SUPLEXA will be administered at Day 1 (baseline), Week 1 and Week 2 (Section 1.2, 
Figure 2). The first 3 subjects in each cohort will be monitored closely at the clinic after each of 
these 3 weekly infusions with follow-up phone calls as described below. 
The first 3 subjects in each cohort will be enroled and subsequently dosed in a staggered manner, 
at least 1 week apart to allow for evaluation of safety. These subjects will be monitored for safety 
in the clinic for 6 hours after each of the 3 weekly infusions and be contacted by phone on a daily 
basis (weekdays) between these weekly infusions and for up to 5 days post final treatment. While 
the Investigator will review safety data on a continual basis, the DSMB will have an opportunity 
to review the first 3 patients in each cohort who receive at least 3 doses of SUPLEXA to further 
evaluate safety and make a recommendation to the Sponsor concerning continuation or 
enrolment, pause in enrolment or study termination. While the DSMB reviews the data from the 
first 3 subjects in each cohort, additional subjects will be screened and enroled into each cohort. 
These additional subjects will not be dosed until the first 3 subjects in their cohort are cleared by 
the DSMB. These subjects will be monitored closely at the clinic for at least 3 hours after each of 
these 3 weekly infusions with follow-up phone calls every 2 business days between treatments 
and for up to 5 days post the 3rd infusion. If any of these subjects experience an adverse event of 
Grade 3 or greater, the longer in-clinic monitoring window of 6 hours post each of the first 3 
weekly infusions and daily calls will be reimplemented as done for the first 3 subjects. During 
the observation period post SUPLEXA administration, subjects will be monitored for any AEs 
and immediate post infusion reaction(s) every 90 minutes. 
The first 15 subjects in the trial will be evaluated for DLTs twice, 1 week after the 1st and 2nd 
dose (prior to administration of 2nd and 3rd dose, respectively). The DLT criteria and DLT 
assessment period(s) are defined in Section 6.5.  
4.1.2.2 
Subsequent Weekly Infusions (SUPLEXA Batch 1 and Batch 2) 
After completion of the first 3 weekly SUPLEXA batch 1 infusions, based on emerging data 
from prior subjects, disease evaluation (as described below), the discretion of the Investigator, 
and in agreement with the subject, treating physician and the Sponsor’s Medical Monitor (or 
designee), the treatment period of SUPLEXA may be extended as follows:  

 
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Subjects will continue to receive SUPLEXA treatments of approximately 5 B cells, every 2 
weeks with a wider window -1 day to +7 days until either, a) depletion of SUPLEXA batch 1 
doses *, or b) disease progression is assessed by the Investigator per  iRECIST v1.1, or c) 
unacceptable toxicity, or other reasons for discontinuation as described in Section 7.2.   
The 5 B cells will be provided as two bags of SUPLEXA targeted at 2.5B cells until all product 
used, unless there is only a single dose unit left, upon which time the subject may receive a 
single bag until more SUPLEXA is manufactured for them. 
An additional SUPLEXA batch #2 may be manufactured for a subject based on (a) last dose of 
batch 1 and the investigator and subject and sponsor agree, then prior to the administration of the 
last SUPLEXA dose, blood can be drawn for SUPLEXA manufacturing of batch 2; or (b) > 2 
weeks and < 8 weeks after the last dose of SUPLEXA administered, blood is collected for batch 
2. 
Note that subjects enroled in SUPLEXA-101,Version 3.0 or 2.0, and had SUPLEXA 
manufacturing started on or before October 31, 2022, may logistically be unable to have the 
consecutive administration of the recommended dosing regimen. These patients are therefore 
exempt from the defined gap in dosing, and the sequential dosing regimen described above. 
However, upon possible restarting additional doses of SUPLEXA, the dosing must be sequential 
until either, a) depletion of SUPLEXA batch 1 doses *, or b) disease progression is assessed by 
the Investigator per  iRECIST v1.1, or c) unacceptable toxicity, or other reasons for 
discontinuation as described in Section 7.2.   
Subjects will be monitored at the clinic for at least 90 minutes (+/- 30 min) after each infusion 
for AE and ISR. 
To account for the well-recognized phenomenon of tumor pseudo-progression or delayed 
response with immunotherapies, subjects may continue to receive SUPLEXA beyond RECIST 
v1.1 defined progression at the discretion of the Investigator. To confirm disease progression 
according to iRECIST, pseudo-progression will be further assessed at the next tumor assessment 
imaging time point after 4 weeks later but not exceeding 8 weeks from the date of initial 
documentation of suspected disease progression, and provided no other drug related adverse 
event occur warranting immediate cessation for clinical reasons. Otherwise, patients will 
continue to be dosed until all doses are used or progression is confirmed, whichever comes first. 
*For each subject treatment duration will be variable and will depend on SUPLEXA 
manufacturing yield. It is anticipated that batch 1 (manufactured during screening)  may be 
sufficient for up to 15 individual 2.5M SUPLEXA doses. In this regimen that would mean 3 
doses as once a week dose, thereafter 3 doses at 2-week intervals, and one dose at the two-week 
interval to exhaust all product made. When batch 1 is depleted, batch 2 will be prepared (as 
described above during screening). During batch 2 manufacturing period, there may be a gap of 
up to 60 days in dosing. 
Decision for treatment extension will be based on: 
• Subject’s overall safety status including AE rate, clinically significant findings from 
safety laboratory (including parameters indicative of TLS, e.g., uric acid elevation), 
physical examination, vital signs; or 

 
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• Subject deriving clinical benefit from treatment with SUPLEXA based on RECIST 
v1.1 and iRECIST for solid tumours and laboratory parameters for haematological 
malignancies; Subjects who are already enroled and received at least 3 weekly doses, 
treatment extension will be based on their latest radiographic scan / laboratory 
evaluation; or 
• Exploratory outcomes (pharmacodynamics and correlative biomarkers), if available 
for review. 
4.1.2.3 
Disease Evaluation 
For subjects in the solid tumours cohort, the on-treatment radiographic assessments of chest, 
abdomen, and pelvis will be performed per standard of care intervals throughout the course of 
the study.  
The first radiographic scan after receiving SUPLEXA will be performed at Week 6-12 weeks 
after the 1st SUPLEXA infusion and thereafter every 6-12 weeks depending on tumour type and 
as clinically indicated per investigator’s discretion. 
These scans should be available for assessment by the Sponsor, if requested. The response 
evaluation will be assessed by the Investigator according to RECIST v1.1 and iRECIST until 
unequivocal radiographic disease progression, or until the subject starts a subsequent anticancer 
therapy (whichever comes first). The tumour assessment (imaging) for confirmation of response 
should be performed no less than 4 weeks after the criteria for response are first met. All 
radiographic scans will be collected and held for possible future retrospective evaluation by 
BICR. 
For subjects in the haematological malignancies cohort, disease evaluation will be conducted 
every 4 weeks, as clinically indicated throughout the study. 
4.1.3 
Follow-up – All Subjects 
All subjects will be followed up every 8 weeks for 48 weeks post last dose of study intervention; 
visits can be done remotely or in-clinic.  
The end of study (EOS) or early termination (ET) visits must be done in person.  
Beyond 48 weeks post last dose of study intervention, subjects will be contacted for survival 
status, disease status and initiation of subsequent anticancer therapies every 12 weeks up to a 
maximum of 24 months after the last dose of study intervention or earlier if the study is 
terminated by the Sponsor. 
Subjects who permanently discontinue study intervention early will be encouraged to remain in 
the study (refer to Section 7.2). Subjects who begin new anti-cancer therapy after discontinuation 
of study intervention will be permanently withdrawn from the study. 
Subjects who withdraw early from the study will be followed-up via phone or in person every 12 
weeks at a minimum or sooner as required by the Investigator to determine OS and PFS. 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
This FIH study will assess the safety and preliminary efficacy of repeated IV doses of 
SUPLEXA in the intended study population (subject with measurable solid tumours and 

 
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haematologic malignancies) in a single-arm, open-label, monotherapy study design. The study 
includes assessments of safety and tolerability, disease evaluation by RECIST v1.1 (solid 
tumours) and disease response (haematologic malignancies) as well as pharmacodynamics / 
biomarker assessment, and immunogenicity characterizations, to determine the recommended 
Phase 2 dose (RP2D) of SUPLEXA for further clinical studies. 
As this is FIH study, to avoid exposing subjects to any unexpected toxicity, the study will 
include a staggered enrolment design whereby 3 subjects will be enroled, SUPLEXA 
manufactured and stored, then doses will be given in a staggered manner, at least one week apart 
to allow evaluation for safety before ling the remaining of the subjects. The first 15 subjects led 
and treated will be evaluated for DLTs after the first and second infusion. 
4.3 
DOSE JUSTIFICATION FOR SUPLEXA THERAPEUTIC CELL DOSE 
The initial cumulative dose selected for this study was based entirely on preclinical mouse 
xenograft studies in which we dosed mice at ~28x the intended human regimen 3 clinical doses 
with an option to extend to 6 doses, with each dose approximately 2.5 B cells (range 1.9-3.9 B 
cells).  Given the complete absence of treatment related adverse events for SUPLEXA in the 
ongoing human study, we propose that after the first 3 doses, administration of up to 14 
additional treatments of 5B cells every 2 weeks will be well tolerated, and the actual number of 
doses depends on the SUPLEXA manufacturing yields for each of 2 patient-specific SUPLEXA 
batches. 
The DSMB will provide an additional review of all safety data and predetermined points in the 
progress of the clinical study. 
4.4 
STUDY DURATION 
Study Duration 
For each subject, the study duration is expected to be as follows: 
Screening:  
Up to 5 weeks 
Treatment: 
Minimally 3 weeks for subjects starting at recommended 
dose. 
Optional  additional doses will be at discretion of the 
investigator in agreement with Sponsor. Subjects may 
receive additional treatment with study intervention 
depending on emerging data and SUPLEXA manufacturing 
yield. 
Follow-up: 
Every 8 weeks for up to 48 weeks from last dose of study 
intervention or earlier if the study is terminated by the 
Sponsor.  
Beyond Week 48, subjects may be contacted every 12 
weeks up to a maximum of 24 months after the last dose of 
SUPLEXA or earlier if the study is terminated by the 
Sponsor. 

 
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5 
ELIGIBILITY CRITERIA 
5.1 
INCLUSION CRITERIA 
Subjects are eligible to be included in the study only if all the relevant criteria for their cohort 
apply: 
Age 
1. Adult subjects at least 18 years of age at the time of signing the PICF. 
Type of Subject and Disease Characteristics 
Solid Tumours 
2. Histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid 
tumour. 
3. Have 1 or more tumours measurable based on RECIST v1.1 as assessed by the local site 
Investigator. Radiographic scans should be obtained within 5 weeks of Screening. Lesions 
situated in a previously irradiated area are considered measurable if objective progression has 
been demonstrated following radiation to such lesions. 
4. Subjects who did not attain a durable response after receiving at least one standard/approved 
therapies which may include chemotherapy, targeted agents, radio-, immuno- conjugates, 
check point inhibitors or where there is no approved therapy. This includes subjects who 
attained a long-term stable disease (SD), or partial response (PR) are eligible. Long term SD 
subjects on a checkpoint inhibitor may continue checkpoint inhibitor (CPI) therapy. 
* Any therapies defined as immunosuppressive require a washout period of at least 4 weeks, defined 
as 4 weeks (28 days) prior to blood collection for SUPLEXA manufacturing and any SUPLEXA dose 
administration. 
Haematologic malignancies 
5. Histologically or cytologically confirmed multiple myeloma, lymphoma, and chronic 
lymphocytic leukemia (collectively termed as haematologic malignancies for the purposes of 
this protocol) which has relapsed or is refractory advanced malignancy for which no curative 
standard therapy exists. 
Pregnancy and Contraception 
Contraception use by men or women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies. Please also refer to Appendix 
4 (Section 10.4) for more information. 
6. Women of childbearing potential must have a negative serum or urine pregnancy test within 
72 hours prior to receiving the first study intervention administration. If the urine test is 
positive or cannot be confirmed as negative, a serum pregnancy test will be required. 

 
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7. For women of childbearing potential who are not abstinent and intend to be sexually active 
with a non-sterilized male partner, must be willing to use an adequate method of 
contraception from 4 weeks prior to the first study intervention administration and 60 days 
following last day study intervention administration and agrees not to donate eggs (ova, 
oocytes) for the purpose of reproduction during this period as it is unknown how activated 
SUPLEXA may impact a pregnancy. Acceptable methods include hormonal contraception 
(oral contraceptives – if on stable dose, patch, implant, and injection), intrauterine devices, or 
double barrier methods (e.g., vaginal diaphragm/ vaginal sponge plus condom, or condom 
plus spermicidal jelly), sexual abstinence or a vasectomized partner. Women may be 
surgically sterile or at least 1-year post-last menstrual period. Note: Abstinence is acceptable 
if this is the usual lifestyle and preferred contraception for the subjects. 
8. Male subjects must be surgically sterile or must agree to use adequate method of 
contraception during the study and at least 90 days following the last day of study 
intervention administration. Male subjects should also refrain from sperm donation during 
this time. 
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the 
subjects. 
Informed Consent 
9. Capable of giving signed PICF. The subject (or legally acceptable representative if 
applicable) provides written informed consent for the study which includes compliance with 
the requirements and restrictions listed in the PICF and in this protocol. 
5.2 
EXCLUSION CRITERIA 
The subjects must be excluded from participating in the study if they meet any of the following: 
Medical Conditions 
1. Known central nervous system (CNS) metastases and/or carcinomatous meningitis. 
2. Prior allogeneic transplant. 
3. Diagnosis of immunodeficiency or is receiving chronic and non-physiological, systemic 
steroid therapy or any other form of immunosuppressive therapy. 
4. Active uncontrolled bacterial, viral, or fungal infection requiring systemic therapy at 
screening or Day 1. 
5. History or current evidence of any condition, therapy, or laboratory abnormality that might 
confound the results of the study, interfere with the subject’s participation for the full 
duration of the study, or is not in the best interest of the subject to participate, in the opinion 
of the treating Investigator. 
6. Any unresolved Grade 2 or greater reversible toxicity from a previous anticancer therapy 
except for alopecia or Grade 2 neuropathy. 
7. Clinically significant cardiovascular disease, including any of the following: 

 
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a. Stroke or myocardial infarction within 6 months prior to first dose in the study. 
b. Presence of unstable angina within 6 months prior to first dose in the study. 
c. Congestive heart failure of New York Heart Association Grade 2 or higher. 
d. History or presence of clinically significant ventricular arrhythmias, or conduction 
abnormality; presence of clinically significant atrial fibrillation and resting bradycardia. 
e. Corrected QT interval (QTcF) of >450 msec (males) or >470 msec (females) using 
Fridericia’s correction formula. 
f. History of congenital long QT syndrome. 
8. Known history of testing positive for human immunodeficiency virus (HIV), and/or positive 
test for Hepatitis B virus surface antigen (HBsAg) and/or positive Hep C antibody result with 
detectable hepatitis C virus (HCV) ribonucleic acid (RNA) indicating acute or chronic 
infection. 
Note: Subjects who have been vaccinated against Hepatitis B and hence are positive only for 
the Hepatitis B surface antibody are permitted to participate in the study. 
9. A serious non-malignant disease (e.g., psychiatric, substance abuse, uncontrolled intercurrent 
illness, etc.) that could compromise protocol objectives in the opinion of the Investigator 
and/or the Sponsor. 
10. At high risk of developing TLS per (Cairo, 2010)). Specifically: 
a) Burkitt’s lymphoma 
b) ALL with LDH > 2xULN or WBC >100 x 109 per µL. 
c) AML with WBC >100 x 109 per µL. 
11. Any other condition that, in the opinion of the Investigator, would prohibit the subject from 
effectively participating in the study. 
Diagnostic Assessments 
12. A performance status ≥2 on the Eastern Cooperative Oncology Group (ECOG) Performance 
Scale (solid tumours cohort) or Karnofsky performance scale of ≥60 (haematologic 
malignancies cohort) 
13. Does not demonstrate adequate organ function as defined as an excursion beyond the 
acceptable limits below. All screening laboratories should be performed at screening and on 
the day of first administration of study therapy. 
System 
Laboratory Value 
Haematological 
Absolute neutrophil count (ANC) 
≤ 50% lower limit of normal (LLN) 
Lymphocyte (WBC) 
≤50% LLN  
Platelets 
<100 × 109/L 
Haemoglobin 
≤9 g/dL or, ≤5.6 mmol/L* 
Renal 

 
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Creatinine OR 
>1.5 times upper limit of normal (ULN) OR 
Measured or calculated**creatinine 
clearance (CrCl) 
Glomerular filtration rate (GFR) can also 
be used instead of creatinine or CrCl 
< 45 mL/min for subject with creatinine levels  
Hepatic 
Total bilirubin 
> 1.5 × ULN OR direct bilirubin ≥ULN for 
subjects with total bilirubin levels > 1.5× ULN 
Aspartate aminotransferase (AST) and 
alanine aminotransferase (ALT) 
>2.5 × ULN (> 5 × ULN for subjects with liver 
metastases) 
* Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) 
transfusion within last 2 weeks 
** Creatinine clearance should be calculated per institutional standard. 
Prior Therapy 
14. Prior radiotherapy within 2 weeks of start of study intervention. Subjects must have 
recovered from all radiation-related toxicities and not require corticosteroids (up to 4 mg/day 
dexamethasone or equivalent will be allowed provided dose is stable for at least 30 days prior 
first SUPLEXA dose and remains stable throughout the trial), and not have had radiation 
pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of 
radiotherapy) to non-CNS disease. 
15. Transfusion of blood products (including platelets or red blood cells) or administration of 
colony stimulating factors (CSF) (including granulocyte CSF [GCSF], granulocyte-
macrophage CSF [GMCSF], or recombinant erythropoietin) within 4 weeks prior to baseline. 
16. Any vaccines (live, attenuated, inactivated or research vaccines) within 30 days of dosing 
with study intervention (refer to Section 6.8.1 for prohibited vaccines). 
Prior/Concurrent Clinical Study Experience 
17. Participation in another clinical study of an investigational agent during the 2 weeks of this 
study’s screening period. 
Note: Subjects participating in an observational study are an exception to this criterion and 
may qualify for the study with Sponsor approval. 
Note: Subjects who have entered the follow-up Period of an investigational study may 
participate if 14 days have elapsed since the last dose of the previous investigational agent 
before blood is drawn for this study. 
Other Exclusions 
18. < 6 months life expectancy at the local site Investigator judgement. 
19. Pregnant or breastfeeding female subjects within the projected duration of the study, starting 
with the first screening visit through 120 days after the last dose of study intervention. 

 
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5.3 
SCREEN FAILURES 
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently entered in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure subjects to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any SAE. 
Individuals who do not meet the criteria for participation in this study for reversible reasons may 
be rescreened. A new subject number will be assigned upon rescreening. For more details on 
specific indications refer to the SUPLEXA IB. 

 
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6 
STUDY INTERVENTION 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study subject according to the 
study protocol. 
6.1 
STUDY INTERVENTION ADMINISTERED 
ARM Name 
Active 
Primary 
Intervention Name 
SUPLEXA therapeutic cells (referred to as SUPLEXA throughout)  
Type  
Autologous cellular therapy comprised of ex vivo activated autologous 
PBMC comprised predominantly of NK, NKT,  T cells, and T cells of 
both CD8-positive and CD4-positive types stored in cryogenic media. 
Dose Formulation 
PlasmaLyte with 28 mM glucose, 3.5% human serum albumin, 50% 
EZ-CPZ (a proprietary cryopreservative medium) and 10% dimethyl 
sulfoxide  
Unit Dose Strength 
Billion cells  
Dosage Level(s) 
Each subject in each cohort will receive a target 2.5 billion SUPLEXA 
cells (range 1.3 to 3.1 billion cells) per infusion of 100 mL of cryogenic 
preservative solution.  
 
Route of 
Administration 
IV 
Administration 
instructions 
Administer weekly (QW) ±2 days for the first 3 weekly infusion and 
thereafter weekly with a range of -1 day to +7 days. 
For prophylactic pre-treatment, refer to Section 6.8.1. 
Thaw a SUPLEXA IV infusion bag.  
Into the SUPLEXA IV infusion bag, slowly transfer approximately 
250 mL (250 grams) of diluent PlasmaLyte (±20% is within the 
acceptable range; i.e., 200-300 grams or mLs). Allow the fluid to transfer 
by gravity.  
Infuse each individual bag’s full volume within 60 minutes into the 
subjects.  
Where doses of 2 bags (5B cells) is given the same process and time is 
used. Thus, infusion of 2 bags is within 2 hours (120min). 
Subjects may ambulate after infusion is complete. 
 
For the first 3 weekly infusions: 

 
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ARM Name 
Active 
• The first 3 subjects in each cohort will be monitored closely at the 
clinic for at least 6 hours after each of the first 3 weekly infusions and 
be contacted by phone on a daily basis (weekdays) between weekly 
infusions for up to 5 days post the 3rd treatment. 
• After the first three subjects , any subject receiving SUPLEXA will 
require a minimally 90minute (+/- 30min) post infusion observation 
and will be monitored for any AEs and immediate post infusion 
reaction(s). 
Refer to Pharmacy manual for detailed administration instructions. 
Sourcing 
Autologous SUPLEXA therapeutic cells are manufactured, labelled, 
stored, and distributed by selected Contract Manufacturing Organisation. 
Packaging and 
Labelling 
Packaging and labelling will be per local regulations. 
6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
• The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention. 
• Only subjects led in the study may receive study intervention and only authorized site staff 
may supply or administer study intervention. All study intervention must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance 
with the labelled storage conditions with access limited to the Investigator and authorized site 
staff. 
• The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance (i.e., 
receipt, reconciliation, and final disposition records). 
• Further guidance and information for the final disposition of unused study interventions are 
provided in the relevant pharmacy manual. 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND BLINDING 
Not applicable; this is an open-label study. 
6.4 
STUDY INTERVENTION COMPLIANCE 
Study intervention will be administered at the study site in the presence of the Investigator or 
designee, as per the SoA (Section 1.3). 
A record of the dose of SUPLEXA administered to each subject must be maintained and 
reconciled with study intervention and compliance records. Minimally, drug start and stop date 
and time, including dates for drug delays will also be recorded in the electronic case report form 
(eCRF). 

 
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6.5 
DOSE LIMITING TOXICITY CRITERIA 
A DLT is defined as the occurrence or start of any of the events listed below during the treatment 
of the first 3 subjects in each cohort that are assessed as related to study intervention 
(SUPLEXA) by the Investigator or the Sponsor. An AE should not be considered as a DLT if it 
can reasonably be attributed to underlying disease, disease progression, concomitant 
medications, or other extraneous causes. Worsening of pre-existing medical illness could be due 
to study intervention and should not be excluded from consideration as a DLT. 
The first 15 subjects will be assessed for DLT. For each subject, the DLT assessment period will 
comprise of 2 parts as follows (Refer to Figure 5):  
• The first DLT assessment period – 1 week after the first dose (prior to administration of the 
second dose). 
• The second DLT assessment period - 1 week after the second dose (prior to the 
administration of the 3rd dose) 
Subjects who withdraw before the end of the DLT assessment period for reasons other than 
DLTs will be replaced. 
All toxicities will be graded by the local site Investigator using National Cancer Institute (NCI) 
common terminology criteria for adverse events (CTCAE) v5.0. 
The following will be considered DLTs: 
Haematologic: 
1. Grade 4 neutropenia lasting for ≥7 days. 
2. Febrile neutropenia is defined as ANC <1000/mm3 with a single temperature of 38.3ºC 
(101°F) or a sustained temperature of 38ºC (100.4°F) for >1 hour. 
3. Grade 4 thrombocytopenia, or Grade 3 thrombocytopenia associated with clinically 
significant bleeding. 
4. Grade 4 anaemia unless there is an alternative explanation e.g., bleeding, etc. 
Non-haematologic: 
1. ≥ Grade 3 non-haematologic toxicity, except for the following Grade 3 events that are 
considered either not an adverse event or events that could be managed with standard of care: 
a) Grade 3 inflammatory reaction attributed to a local anti-tumour response (e.g., 
inflammatory reaction such as pain, irritation, or localized rash at sites of metastatic 
disease, lymph nodes, etc.). 
b) Grade 3 fatigue lasting ≤ 3 days. 
c) Grade 3 diarrhea, nausea, or vomiting lasting ≤3 days without or with use of anti-emetics 
or anti-diarrheals per standard of care. 
d) Grade 3 rash and/or pruritis without use of corticosteroids or anti-inflammatory agents 
per standard of care. 

 
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2. Any Grade 3 or Grade 4 non-haematologic laboratory value if: 
a) Clinically significant medical intervention is required to treat the subject and does not 
resolve within 72 hours, or 
b) Potential drug-induced liver toxicities with laboratory parameters as described below 
− ≥ Grade 3 and above elevation in ALT or AST if an alternative explanation other 
than the study intervention is not available. 
− ≥ Grade 3 and above elevation of total bilirubin of any duration if an alternative 
explanation other than the study intervention is not available. 
− Grade 2 elevation AST/ALT with concurrent elevation of total bilirubin >2 ULN 
or INR >1.5 ULN if an alternative explanation other than the study intervention 
is not available. 
6.5.1 
Dose Modifications and Individual Stopping Rules due to DLT 
All eligible subjects are planned to receive a minimal cumulative dose of approximately 7.5 
billion cells of SUPLEXA administered as target of 2.5 billion cells per individual SUPLEXA 
doses. The first 3 doses will be administered at least 1 week apart (unless delayed due to DLTs 
as described below) at Day 1 (baseline), Week 1 and Week 2.  
During the study, the cumulative dose of study intervention will not be modified unless triggered 
by rules governing DLT (as described below); that is, subjects experiencing a DLT which does 
not resolve within 3 weeks or 2 DLTs may only receive 1 or 2 infusions, each 2.5 billion cells 
(for these subjects, cumulative dose may range between 2.5 billion cells to 5.0 billion cells.  
The DSMB will convene to review all available data collected during the DLT assessment 
period(s) including Investigator’s impressions and provide an additional layer of oversight. The 
DSMB will make recommendations to the Sponsor on enrolment modifications. 
The rules below will apply independently to the solid tumours and haematologic malignancies in 
parallel and for each subject in the study.  
1. Enrol a subject and administer 1st dose on Day 1. Assess for DLTs during the first DLT 
assessment period (1 week post 1st infusion).  
a) No DLT, continue to 2nd dose at Week 1 (Day 8) – refer to item 2 below,  
b) Subject experienced a DLT (per DLT criteria in Section 6.5) and the is event resolved 
within 3 weeks to baseline levels (Grade 1 or lower)? 
i) Yes, continue to 2nd dose – refer to item 2 below 
ii) No, permanently discontinue study intervention and subject will continue to be 
followed-up as part of the study (unless withdraw consent and start other anti-cancer 
therapies) as described in Section 7.2. 
2. Administer 2nd dose. Assess for DLTs during the 2nd DLT assessment period (1 week post 2nd 
infusion) 
a) No DLT, continue to 3rd dose – refer to item 3 below  

 
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b) Subject experienced a DLT (per DLT criteria in Section 6.5)  
i) If first occurrence of DLT and the event resolved within 3 weeks to baseline levels 
(Grade 1 or lower)? 
− Yes, continue to 3rd dose – refer to item 3 below 
− No, permanently discontinue study intervention and subject will continue to be 
followed-up as part of the study (unless withdraw consent and start other anti-
cancer therapies) as described in Section 7.2. 
ii) If second occurrence of DLT in the same subject, permanently discontinue study 
intervention and subject will continue to be followed-up as part of the study (unless 
withdraw consent and start other anti-cancer therapies) as described in Section 7.2. 
3. Administer 3rd dose and follow-up subject per SoA (Section 1.3).  

 
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Figure 5: Individual DLT Stopping Rules and Dose Modification of Study Intervention  
 
Abbreviations: D = dose; DLT = dose limiting toxicities; S = stop

 
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6.6 
TOXICITY MANAGEMENT 
Guidelines for toxicity management associated or possibly associated with SUPLEXA are 
located in the appendices for: 
• CRS toxicity (Appendix 6, Section 10.7) 
• TLS toxicity (Appendix 7, Section 10.8) 
 
6.7 
TREATMENT OF OVERDOSE 
Any overdose of study intervention is unlikely given the premade doses, but should they occur 
must be recorded in the eCRF including quantity of the excess dose and the duration of the 
overdose. AEs associated with an overdose or incorrect administration of study intervention 
should be recorded in the AE eCRF. An overdose will not be considered an SAE unless the 
outcome of the overdose meets seriousness criteria. 
For this study, any dose of study intervention greater than the number of cells in a given infusion 
bag will be considered an overdose as will any administration greater than specified in a 
particular dose reduction cohort. 
In the event of overdose, the subject should be observed closely for signs of toxicity. Appropriate 
supportive treatment should be provided if clinically indicated. 
6.8 
CONCOMITANT GENERIC THERAPY 
Any medication or vaccine (including over the counter or prescription medicines, vitamins, 
and/or herbal supplements) that the subject is receiving within 4 weeks before the first dose of 
study intervention through 24 weeks after the last dose of study intervention must be recorded 
along with: 
• Name of medication/therapy (generic name) 
• Reason for use 
• Dates of administration including start and end dates 
• Dosage information including dose and frequency 
Concomitant medications administered 24 weeks after the last dose of study intervention should 
be recorded for SAEs. 
Concomitant medications necessary for the health and well-being of the subject and that do not 
interfere with study assessments are permitted during the study at the Investigator’s discretion. 
All treatments that the Investigator considers necessary for a subject’s welfare may be 
administered at the discretion of the Investigator in keeping with the community standards of 
medical care. This includes the use of appropriate medications for the treatment of AEs and/or 
concurrent illnesses under the direction of the Investigator. All medications must be recorded in 
the source and on the appropriate eCRFs. Start of new medications of any type (over the counter 
or prescription) during the study however is strongly discouraged as it can be deemed 
confounding. 

 
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Concurrent use anti-androgen therapies subjects with prostate cancer and anti-estrogen therapies 
for subjects with breast cancer is allowed. Bisphosphonate IV (i.e., zoledronic acid) or 
denosumab subcutaneous (SC) therapy must be initiated prior or within the first 60 days of the 
first administration of the study intervention. Oral bisphosphonate may be initiated at any point 
in the study for the treatment of osteoporosis.  
Concurrent use of continued targeted therapies and immune checkpoint inhibitor therapies (e.g., 
anti-PD-1, anti-PD-L1 or anti-CTLA4) may be allowed provided the subject was on a stable dose 
for at least 3 months prior to enrolment and had at least a stable disease response. 
Concurrent use of dexamethasone (up to 4 mg/day) may be allowed provided the subject was on 
a stable dose for at least 30 days. 
The Sponsor’s Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
6.8.1 
Prophylaxis 
For cytotoxic chemotherapies, allopurinol administration is recommended 24 hours prior to 
initiation of treatment with SUPLEXA because of the immediate action of the cytotoxic 
chemotherapy. For cellular therapies however, cells require at least a day to migrate out of the 
circulation to the tumour bed and synchronous tumour lysis will be delayed. Therefore, 
allopurinol will be administered concomitantly with each SUPLEXA dose, and between doses as 
directed by the investigator. 
The following pretreatment regimen is suggested, although a different regimen based on local 
standard of care/ institutional practices is permitted: Approximately 1 hour (60 min ± 15 min) 
before each SUPLEXA infusion, all subjects will receive single administration of: 
• Acetaminophen 1000 mg PO (for potential fever)  
• Diphenhydramine 12.5 mg PO (for potential rash) 
• Allopurinol 100 mg (IV or PO) (for potential tumour lysis syndrome in subjects 
who are at intermediate risk for TLS; refer to Figure 6). This should be followed, 
unless the investigator determines continued oral dosing of allopurinol is required. 
6.8.2 
Prohibited Medications and Treatment 
Medications or vaccinations specifically prohibited in the exclusion criteria are not allowed 
during the ongoing study. If there is a clinical indication for any medication or vaccination 
specifically prohibited during the study, discontinuation from study intervention may be 
required. The Investigator should discuss any questions regarding this with the Sponsor’s 
Medical Monitor. The final decision on any supportive therapy or vaccination rests with the 
Investigator and/or the subject's primary physician. However, the decision to continue the subject 
on study intervention requires the mutual agreement of the Investigator, the Sponsor, and the 
subject. Subjects who, in the assessment of the Investigator, require the use of any of the 
prohibited treatments for clinical management should be removed from the study. 
The following medications are excluded from concomitant use for all subjects during the study: 
• Vaccines: 

 
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− Live vaccines including, but are not limited to measles, mumps, rubella, 
varicella/zoster, yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and 
typhoid vaccine. 
− Attenuated vaccines, e.g., FluMist® 
− Inactivated vaccines, e.g., COVID-19 vaccine; Please also refer to Section 10.9 
(Guidance to Address Global Health Emergencies) 
− Research vaccines, including any investigative COVID-19 vaccine studies 
Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and 
are allowed. 
• Concurrent use of immunostimulatory agents, including but not limited to IFN-α, 
IFN-γ, or interleukin 2 (IL-2) with study intervention, during the entire study. 
• Any investigational agent, other than SUPLEXA. 
• Immunosuppressive anticancer therapies (chemotherapy, radiation therapy, biological 
therapy or immunotherapy which are not specified in this protocol) or approved by 
the Sponsor will be excluded. Herb supplements that are used for the treatment of the 
malignancy under the study are not allowed.  
Note: Palliative radiation therapy for pain management or for symptomatic solitary 
lesion if not new lesion may be allowed at the Investigator’s discretion. 
Note: Surgery to bone lesion to prevent the risk of fracture will be allowed. 
• Concurrent use of immunosuppressive medications, including but not limited to 
cyclophosphamide, azathioprine, or methotrexate. 
6.8.3 
Rescue Medications and Supportive Care 
Subjects should receive appropriate supportive care measures as deemed necessary by the 
treating Investigator. 

 
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7 
STOPPING RULES, DISCONTINUATION OF STUDY INTERVENTION 
AND SUBJECT WITHDRAWAL FROM THE STUDY 
7.1 
STUDY STOPPING RULES 
Enrolment in this study will be stopped at any time for safety reasons. 
The study includes DLT Stopping rules (refer to Section 6.5.1). In addition, enrolment and 
treatment with SUPLEXA will be temporarily suspended for any of the following reasons 
pending review and recommendations from the DSMB: 
• 
Any death that is not due to disease progression within 30 days after receiving SUPLEXA 
will result in a hold of further enrolment, until an investigation into the cause of death is 
performed by DSMB. If it is determined that the death was not related to the study 
intervention, then enrolment may restart. If the relationship between SUPLEXA infusion 
and death is not clear, or it appears that the death may be related to study intervention, 
enrolment will be held until further review. Refer to Section 8.3.7. 
• The occurrence of two ≥ Grade 4 DLTs in 2 study subjects. 
• At least 3 cases of ≥Grade 3 of the following events assessed as related to study intervention: 
− Immunological related events 
− CRS 
− TLS 
Suspension of the study will entail stopping the enrolment of new subjects and maintaining 
enroled subjects in the study. Suspension of the study will not entail cessation of dosing in 
subjects who did not complete the 3-dose administration unless so directed by the regulatory 
agencies or advised by the DSMB and agreed to by the Sponsor. The suspension will remain in 
effect until the case(s) and supporting information have been discussed between the Sponsor and 
the DSMB and the relevant regulatory agencies, if applicable, with a decision made to either 
resume the study or stop the study. If a decision is made to stop the study, all subjects will 
immediately discontinue dosing with study intervention and will undergo a follow-up visit as 
specified in the SoA. 
The DSMB will review safety data at regular intervals, and can recommend, in its judgment, 
halting the study for any substantial imbalance in AEs. Sponsor additionally reserves the right to 
stop the study at any time for any reason. The regulatory health authorities and Australian 
Human Research Ethics Committee (HREC) will be notified in the event the study is stopped. 
7.2 
DISCONTINUATION OF STUDY INTERVENTION 
In some instances, it may be necessary for a subject to permanently discontinue study 
intervention. Please also refer to stopping rules described in Section 7.1. 
A subject must permanently discontinue study intervention if they meet one of the following 
individual stopping rules: 
• Any Grade 4 life threatening events assessed as related to study intervention. 
• ≥Grade 3 immunological-related event assessed as related to study intervention (refer to 
Section 7.2.1) 

 
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A subject may also discontinue study intervention for reasons including but not limited to: 
• Adverse event 
• Lost to follow-up 
• Non-compliance with study drug 
• Physician decision 
• Pregnancy (refer to Section 7.2.2) 
• Progressive disease 
• Protocol deviation 
• Study terminated by Sponsor 
• Withdrawal by subject 
• Death 
Permanent discontinuation of study intervention does not mean withdrawal from the study, and 
the subject will be encouraged to remain in the study, complete the ET visit and then continue to 
complete all study visits as per the SoA, including all follow-up visits.  
For subjects who have discontinued study intervention due to reasons other than disease 
progression, tumour assessment will be continued at the protocol-specified schedule until 
documented disease progression or initiation of subsequent anticancer therapy or until 24 months 
after the last dose of study intervention. 
The primary reason for discontinuation from study intervention should be documented on the 
appropriate eCRF. 
7.2.1 
Immunological effects: Action and Follow-Up Assessment 
SUPLEXA impact on normal tissues is a theoretical concern but one which was not observed in 
nonclinical studies conducted in the organoid PDX or xenograft or PDX animal models. A 
subject experiencing an immunological event of CTCAE Grade 3 or greater will permanently 
discontinue study intervention. 
7.2.2 
Pregnancy 
A subject must permanently discontinue study intervention if they become pregnant but will 
advance to the post-treatment observational component of this study. See Appendix 4 
(Section 10.4) and Section 8.3.5 for additional details. 
7.3 
SUBJECT WITHDRAWAL FROM THE STUDY 
Subjects have the right to withdraw from the study at any time and for any reason without 
prejudice to their future medical care by the Investigator or at the institution. 
A subject may withdraw from the study for reasons including but not limited to: 
• Withdrawal by subject 
• Initiation of prohibited medications (anti-cancer treatment) 

 
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• Lost to follow-up 
• Study terminated by Sponsor 
• Death 
At the time of withdrawal from the study, if possible, an ET visit should be conducted, as shown 
in the SoA (Section 1.3). The subject will be permanently discontinued both from the study 
intervention and from the study at that time. 
If the subject 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 subject withdraws from the study, he/she/they may request destruction of any samples taken 
and not tested, and the Investigator must document this in the site study records. 
7.4 
LOST TO FOLLOW UP 
A subject will be considered lost to follow-up if he/she/they repeatedly fail to return for 
scheduled visits and are unable to be contacted by the study site. 
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in 
the study. 
• Before a subject is deemed lost to follow up, the Investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, 
if necessary, a certified letter to the subject’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the subject’s 
medical record. 
• Should the subject continue to be unreachable, he/she/they will be considered to have 
withdrawn from the study. 

 
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8 
STUDY ASSESSMENTS AND PROCEDURES 
• Study procedures and their timing are summarized in the SoA (Section 1.3). Protocol 
waivers or exemptions are not allowed. 
• Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the subject should continue or discontinue study 
intervention. 
• Adherence to the study design requirements, including those specified in the SoA 
(Section 1.3), 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 subject’s routine clinical management (e.g., blood 
count) and obtained before signing of the ICF may be utilized for screening or baseline 
purposes provided the procedures met the protocol-specified criteria and were performed 
within the time frame defined in the SoA (Section 1.3). 
• Some visits/study procedures may be done remotely via virtual visits (telemedicine) or at 
home health visits. Refer to Appendix 6 (Section 10.9) and Study Reference Manual for 
more details 
8.1 
EFFICACY ASSESSMENTS 
Planned time points for all efficacy assessments are provided in the SoA (Section 1.3). 
8.1.1 
RECIST v1.1 (Solid Tumours Cohort only) 
Objective response to treatment with SUPLEXA will be evaluated using RECIST v1.1 
(Eisenhauer, 2009) as described in Appendix 5 Section 10.5. Radiographic imaging will be 
assessed locally by the Investigator; refer to Section 10.5.2 for methods of measurements. 
8.1.2 
Disease Response Assessments (Haematologic Malignancies Cohort only) 
Haematologic malignancies (multiple myeloma, lymphoma, and chronic lymphocytic leukemia) 
disease response will be assessed by the Investigator every 4 weeks (±3 days) per standard of 
care. 
8.2 
SAFETY ASSESSMENTS 
Planned time points for all safety assessments are provided in the SoA (Section 1.3). 
8.2.1 
Physical Examinations 
• A complete physical examination will include, at a minimum, assessments of the 
cardiovascular, respiratory, gastrointestinal, and neurological systems. Height and 
weight will also be measured and recorded. 

 
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• A brief physical examination will include, at a minimum, assessments of the skin, 
lungs, cardiovascular system, and abdomen (liver and spleen). 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
8.2.2 
Vital Signs 
• Oral, aural, or surface temperature, pulse rate, respiratory rate, and blood pressure 
will be assessed. 
• Blood pressure and pulse measurements will be assessed with a completely 
automated device. Manual techniques will be used only if an automated device is not 
available. 
• Blood pressure and pulse measurements should be preceded by at least 5 minutes of 
rest for the subject in a quiet setting without distractions (e.g., television, cell phones). 
• Vital signs will be measured in a semi-supine position after 5 minutes rest and will 
include temperature, systolic and diastolic blood pressure, and pulse. 
8.2.3 
Electrocardiograms 
• 12-lead ECG will be obtained as outlined in the SoA (Section 1.3) using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and 
QTc intervals. 
8.2.4 
Clinical Safety Laboratory Assessments 
• See Appendix 2 (Section10.2) for the list of clinical laboratory tests to be performed 
and to the SoA (Section 1.3) for the timing and frequency. 
• Abnormal laboratories will be classified according to the NCI CTCAE, version 5.0. 
• The Investigator must review the laboratory report, document this review, and record 
any clinically significant changes occurring during the study as an AE. If a laboratory 
finding is abnormal but not clinically significant (NCS) at baseline, postbaseline 
laboratory abnormalities will be reported as an AE only if there is worsening 
compared to baseline. 
• The laboratory reports must be filed with the source documents. 
• Abnormal laboratory findings associated with the underlying disease are not 
considered clinically significant unless documented by the Investigator. 
• All laboratory tests with values considered clinically significantly abnormal 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 or 
medical monitor. 
− If such values do not return to normal/baseline within a period judged reasonable 
by the Investigator, the aetiology should be identified, and the Sponsor notified. 

 
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− All protocol-required laboratory tests, as defined in Appendix 2 (Section 10.2), 
must be conducted in accordance with the laboratory manual and the SoA 
(Section 1.3). 
− If laboratory values from non-protocol specified laboratory tests performed at the 
institution’s local laboratory require a change in subject management or are 
considered clinically significant by the Investigator (e.g., SAE or AE or dose 
modification), then the results must be recorded. 
8.2.5 
Performance Status 
ECOG Performance Status (Solid Tumours Cohort) 
The Eastern Cooperative Oncology Group (ECOG) Performance Status will be used to assess 
subject’s performance status (Table 2). 
Table 2: 
Eastern Cooperative Oncology Group (ECOG) Performance Status 
Grade ECOG 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
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 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up 
and about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 
5 
Dead 
Karnofsky Performance Status (Haematologic malignancies Cohort) 
Karnofsky performance status scale will be performed at screening to assess subject’s functional 
impairment, ranging from 100 to 0, in increments of 10, where 100 is normal health and 0 is 
death (Table 3). To be eligible to participate in this study, subjects must have a Karnofsky 
performance status of ≥60%. This scale was shown to be valid in assessing geriatric population 
(Crooks, 1991). 

 
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Table 3: 
Karnofsky Performance Status 
Able to carry on normal activity and to work; no 
special care needed. 
100 Normal; no complaints; no evidence of 
disease. 
90 
Able to carry on normal activity; minor 
signs or symptoms of disease. 
80 
Normal activity with effort; some signs or 
symptoms of disease. 
Unable to work; able to live at home and care for 
most personal needs; varying amount of 
assistance needed. 
70 
Cares for self; unable to carry on normal 
activity or to do active work. 
60 
Requires occasional assistance but is able to 
care for most of their personal needs. 
50 
Requires considerable assistance and 
frequent medical care. 
Unable to care for self; requires equivalent of 
institutional or hospital care; disease may be 
progressing rapidly. 
40 
Disabled; requires special care and 
assistance. 
30 
Severely disabled; hospital admission is 
indicated although death not imminent. 
20 
Very sick; hospital admission necessary; 
active supportive treatment necessary. 
10 
Moribund; fatal processes progressing 
rapidly. 
 
0 
Dead 
 
8.3 
ADVERSE EVENTS (AES), SERIOUS ADVERSE EVENTS (SAES), AND OTHER SAFETY 
REPORTING 
AEs will be classified according to the NCI CTCAE, version 5.0. 
The definitions of adverse events (AEs) and serious adverse events (SAEs) can be found in 
Appendix 3 (Section 10.3). 
AEs will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or the 
subject's legally authorized representative). 
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study intervention or study procedures, or that 
caused the subject to discontinue the study intervention (see Section 7). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 3 
(Section 10.3). 

 
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8.3.1 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the signing of the ICF until the follow-up visit at the 
time points specified in the SoA (Section 1.3). 
Table 4 below summarizes the different observation periods for AEs, and SAEs. 
Table 4: 
Adverse Event Reporting Periods and Reporting Timelines to the Sponsor 
Type of 
Event 
Adverse Event  
Serious Adverse Event 
Reporting 
period 
From first dose of the study intervention 
until 30 days after the last dose of study 
intervention discontinued or before 
initiation of subsequent anticancer 
therapies, whichever comes first. 
From consent until 30 days after the last 
dose of study intervention discontinued 
for all SAEs, and any time after that 
window if the SAEs are believed to be 
related to study intervention. 
Reporting 
Timelines to 
the Sponsor 
Entered the clinical database on an ongoing 
basis. 
Within 24 hours. 
All SAEs will be recorded and reported to the Sponsor or designee immediately and under no 
circumstance should this exceed 24 hours, as indicated in Appendix 3 (Section 10.3). The 
Investigator will submit any updated SAE data to the Sponsor within 24 hours of it being 
available. 
Medical occurrences that begin before the start of the study intervention but after obtaining 
informed consent will be recorded on the Medical History section of the eCRF not the AE 
section, unless the medical occurrence is an SAE. 
The Investigator is responsible for ensuring that all AEs are properly captured in the subject’s 
medical records and reported in the eCRF. 
Investigators are not obligated to actively seek information on AEs or SAEs after conclusion of 
the study participation. However, if the Investigator learns of any SAE, including a death, at any 
time after a subject has been discharged from the study, and he/she considers the event to be 
reasonably related to the study intervention or study participation, the Investigator must promptly 
notify the Sponsor. 
8.3.2 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrences. 
8.3.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event is 
otherwise explained, or the subject is lost to follow-up (as defined in Section 7.4). Further 
information on follow-up procedures is provided in Appendix 3 (Section 10.3). 

 
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8.3.4 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects and the safety of a 
study intervention under clinical investigation are met. 
• The Sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The Sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, HREC, and Investigators. 
• An Investigator who receives an Investigator safety report describing an SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the Sponsor will 
review and then file it along with the IB and will notify the HREC, if appropriate 
according to local requirements. 
8.3.5 
Pregnancy 
• Details of all pregnancies in female subjects will be collected as outlined in Appendix 4 
(Section 10.4). 
• If a pregnancy is reported, the Investigator will record pregnancy information on the 
appropriate form and submit it to the Sponsor within 24 hours of learning of the female 
subject pregnancy. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be reported 
as an AE or SAE. 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, foetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported. 
• The subject will be followed to determine the outcome of the pregnancy. The Investigator 
will collect follow-up information on the subject and the neonate, and the information 
will be forwarded to the Sponsor. 
• Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the Investigator will be reported to the Sponsor as described in 
Section 8.3.4. While the Investigator is not obligated to actively seek this information in 
former study subjects, he or she may learn of an SAE through spontaneous reporting. 
• Any female subject who becomes pregnant while participating in the study will 
discontinue study intervention or be withdrawn from the study. 
8.3.6 
Disease Progression 
Clinical signs or symptoms associated with progression of underlying malignancy are not 
reported as AEs if they are clearly consistent with the suspected progression of the underlying 
malignancy. Hospitalization solely due to the progression of underlying malignancy should NOT 
be reported as an SAE. Clinical symptoms of progression may be reported as AEs if the 
symptom cannot be determined as exclusively due to the progression of the underlying 
malignancy or does not fit the expected pattern of progression for the disease under study. The 
site should report clinical signs/symptoms that have met the SAE definition within 24 hours of 

 
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learning the event if the aetiology is not clear at the time of the onset. If the subsequent workup 
has revealed that the reported event is associated with progression of underlying malignancy, the 
follow-up information should be submitted, and event term should be updated to the cause that 
led to the hospitalization instead of disease progression. For example, if a subject is hospitalized 
with shortness of breath that is determined to be associated with worsening of pleural effusion 
during the subsequent workup, pleural effusion could be used an event term instead of disease 
progression. SAE that has been reported should not be deleted from the database if the event is 
determined to be associated with disease progression with subsequent workups. 
If there is any uncertainty about an AE being due only to the disease under study, it should be 
reported as an AE or SAE. 
8.3.7 
Death Events 
All death events will require completion of a death data collection page within the eCRF. 
Timelines for reporting of death events are identical to the requirements for SAE reporting. 
(Appendix 3, Section 10.3). Events resulting in death will be an SAE regardless of association to 
disease progression (Section 8.3.6). Death is an outcome and should not be reported as an event 
term. The event that leads to the death should be reported as the SAE term. 
8.4 
PHARMACODYNAMICS AND CORRELATIVE BIOMARKERS 
Whole blood will be collected during study as specified in the SoA and the study-specific 
Laboratory Manual. The main objective is to characterize the immune phenotype and function of 
the subject PBMC before each SUPLEXA administration by PBMC composition and cytokine 
levels in peripheral blood samples, as well as immunophenotyping (e.g., PBMC profiling, 
cytokine, and tumour pharmacodynamics marker assessment). Additional, chronological blood 
samples will also be evaluated as above.  
Samples may be stored at a facility selected by the Sponsor, to enable downstream batch 
analysis, to the maximum limit permitted according to local regulations following subject’s last 
visit for the study. 
Residual blood samples may be stored for identification of factors or profiles that correlate with 
measures of response to study intervention. 
For more details on the procedures, please refer to the study-specific Laboratory Manual. 

 
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9 
STATISTICAL CONSIDERATION 
9.1 
SAMPLE SIZE DETERMINATION 
Approximately 60 subjects will be enroled with a cap of about 8 subjects per individual tumour 
type (e.g., melanoma, breast, prostate, lung, haematological malignancies, etc.). If promising 
anti-tumour activity coupled with acceptable safety is observed, overall sample size and/or cap 
per tumour type may be expanded. 
9.2 
POPULATION FOR ANALYSES 
For purposes of analysis, the following populations are defined: 
Population 
Description 
DLT evaluable 
Population  
All subjects who receive at least 1 dose of study intervention and 
experience a DLT. 
Safety Analysis Set 
All subjects who receive at least 1 dose of study intervention. 
Response Evaluable 
Population 
All subjects who receive at least 1 dose of study intervention and have 
measurable disease at baseline and at least one post-baseline tumour 
assessment per RECIST v1.1. 
9.3 
STATISTICAL METHODS 
Detailed methodology for summary and statistical analyses of the data collected in this study will 
be documented in a statistical analysis plan (SAP), which will be maintained by the Sponsor. The 
SAP may modify the plans outlined in the protocol; however, any major modifications will also 
be reflected in a protocol amendment. The SAP will be finalized before database lock and will 
describe the analysis populations to be included in the analyses, and procedures for accounting 
for missing, unused, and spurious data. The SAP will supersede this section of protocol in the 
event of divergence. This section is a summary of the planned statistical analyses of the primary 
and secondary endpoints. 
9.3.1 
General 
Statistical analyses will be performed using SAS® v9.4 or higher (SAS Institute, Cary NC, USA) 
and all analysis will be described in the SAP finalized before database lock. 
The standard summary statistics for continuous variables are sample size (n), mean, standard 
deviation (SD), median, minimum, and maximum. The standard summary statistics for 
categorical variables are frequencies and percentages. Time to event variables will be 
summarized using the Kaplan-Meier method. Where confidence limits are appropriate, the 
confidence level will be 95% (two-sided), unless otherwise stated. 
Individual data (including relevant derived variables) will be presented by parameter in listings. 
Results of statistical analyses, descriptive summary statistics and supportive listings will also be 
presented. 

 
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9.3.2 
Efficacy Analysis 
Solid Tumour Cohort 
The secondary endpoint of ORR will be defined as the proportion of subjects with BOCR of 
either a CR or PR as assessed by the Investigator using RECIST v1.1 in the Response Evaluable 
Population as both unconfirmed or confirmed status. ORR will be reported as a proportion along 
with the corresponding 2-sided 95% Clopper-Pearson exact CI. 
A sensitivity analysis of the primary endpoint will be performed in the Response Evaluable 
Population. 
Other secondary and exploratory endpoints are defined as follows for the whole cohort or 
analysed by tumour type: 
Secondary 
• TTP will be defined as the time from the first dose of study intervention to the first 
documented date of disease progression. 
Exploratory 
• DOR will be defined as the time from the first date of objective response (CR or PR) 
to the first documented date of disease progression or the date of death due to any 
cause, whichever occurs first. Only subjects with a CR or PR will be included. 
• TTR will be defined as the time from the first dose of study intervention to the first 
date of objective response (CR or PR). Only subjects with a CR or PR will be 
included. 
• CBR will be defined as the proportion of subjects with a CR or PR or SD at 6 months. 
• PFS will be defined as the time from the first dose of study intervention to the first 
documented date of disease progression or the date of death due to any cause, 
whichever occurs first. 
• OS will be defined as the time from the first dose of study intervention to the date of 
death due to any cause. 
• Biomarker change from baseline with time as % and absolute. 
Main analyses of the above response-related endpoints will be performed in the Efficacy 
Evaluable Population using Investigator-assessed response. Sensitivity analyses of the above 
response-related endpoints may be performed in the Response Evaluable Population using 
Investigator-assessed response. If response is also assessed by BICR, further sensitivity analyses 
of the above response-related endpoints may be performed using BICR-assessed response. 
CBR will be analysed in a similar manner as the primary endpoint of ORR. 
Time-to-event endpoints (DOR, TTR, PFS, TTP, and OS) will be summarized using Kaplan-
Meier estimates. If estimable, median, 25th, and 75th percentiles and associated 95% CIs will be 
presented. A Kaplan-Meier curve will also be generated for each time-to-event endpoint. For 
time-to event endpoints, censoring rules will be applied as follows. DOR will be censored at the 
last tumour assessment date. PFS and TTP will be censored at the last tumour assessment date 

 
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for subjects with post-baseline assessment (s). OS will be censored at the last known date alive 
for subjects. 
Haematologic malignancies Cohort 
Statistical analyses will be descriptive and graphical in nature. If sample size permits, complete 
remission will be summarized descriptively using Kaplan-Meier medians and quartiles. 
9.3.3 
Safety and Tolerability Analysis 
Safety outcomes will be analysed at the end of each study intervention period as well as over the 
course of the entire study. 
The safety assessment will be based on the frequency of adverse events, on the observation of 
clinically significant abnormalities of laboratory values, concomitant medication use, vital signs, 
and physical examination data in the Safety analysis set. 
Adverse events: Overall AE as well as AE classified by system organ class and preferred 
terminology according to the Medical Dictionary for Regulatory Activities (MedDRA) will be 
summarized. Additionally, AE will be summarized by severity and relation to study intervention. 
SAEs and AEs leading to discontinuation will also be summarized. 
Other safety data: These data will be summarized by presenting the proportions of subjects with 
clinically significant abnormalities or changes from baseline values. Laboratory data will be 
presented in data listings and summarized. 
9.3.4 
Other Analyses 
Additional details for pharmacodynamics and biomarker exploratory analyses will be described 
in the SAP finalized before database lock. 
9.3.5 
Interim Analysis 
Open label study and no interim analysis is planned. 
9.3.6 
Data Safety Monitoring Board (DSMB) 
The DSMB, a specific independent committee for the study with external representation 
composed of at least 3 members and include experts in the field of oncology and clinical studies, 
or biostatistics. Other members may be invited as needed. The DSMB will regularly monitor 
overall safety on an unblinded basis, as well as general aspects of study conduct, to ensure that 
the benefits and risks of study participation remain acceptable.  
The DSMB will evaluate all relevant toxicity data and confirm that the principal investigator is 
reporting all serious, unexpected, or other related toxicities to the regulatory authorities. 
During the conduct of the study, the DSMB will periodically be asked to advise the Sponsor 
regarding modification, continuation, or discontinuation of the study based on the review of the 
study safety data. Efficacy data will not be provided to the DSMB. 
Details on the composition of the DSMB, meeting structure, schedule, and procedures, the 
content and format of DSMB reports, and other relevant details will be determined in 
consultation with DSMB members and detailed in a separate DSMB charter. 

 
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10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
APPENDIX 1: REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
10.1.1 
Regulatory and Ethical Considerations 
10.1.1.1 
Regulatory Requirements 
The Sponsor, Alloplex Australia Pty. Ltd., is the legal Australian Sponsor for the study and will 
fulfil the obligations that this role entails. The Sponsor shall, to the extent required by the 
applicable laws and regulations, interact with TGA in connection with this study. The planned 
regulatory pathway for this study is through the Clinical Trial Notification (CTN) scheme. Aside 
from approval by the HREC and notification of the TGA no other regulatory approval will be 
required. 
10.1.1.2 
Ethical Conduct of the Study 
This study will be conducted in accordance with the principles of the current Declaration of 
Helsinki (Recommendations guiding Medical Doctors in Biomedical Research Involving Human 
Subjects) and with the NHMRC National Statement on Ethical Conduct in Research Involving 
Humans (2007, including current updates, 2018). The conduct of the study will be in accordance 
with the Integrated Addendum to International Council for Harmonisation (ICH) E6 (R1), 
Guideline for GCP E6 (R2) adopted by TGA (2000), annotated with comments by the TGA 
(2018). 
This study will be conducted under a protocol reviewed and approved by an HREC at each site 
and investigations will be undertaken by scientifically and medically qualified persons, where 
the benefits of the study are in proportion to the risks. At each study site, the study will be 
overseen by an Investigator who, prior to study start at the site, will have read, and agreed 
understanding of the protocol requirements and will agree to conduct the study in accordance 
with the above. 
10.1.1.3 
Ethics Review 
The final study protocol, including the final version of the PICF, must be approved, or given a 
favourable opinion in writing by an HREC as appropriate. The Investigator must submit written 
approval to the Sponsor before he or she can enrol any subject/subject into the study. 
The Investigator is responsible for informing the HREC of any amendment to the protocol in 
accordance with local requirements. In addition, the HREC must approve all advertising used to 
recruit subjects for the study. The protocol must be re-approved by the HREC upon receipt of 
amendments and annually, as local regulations require. 
The Investigator is also responsible for providing the HREC with reports of any reportable 
serious adverse drug reactions from any other study conducted with the study intervention. The 
Sponsor will provide this information to the Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the 
HREC according to local regulations and guidelines. 

 
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10.1.1.4 
Sponsor and Investigator Obligations 
Investigator Obligations 
The Investigator and study staff are responsible for maintaining a comprehensive filing system of 
all study-related (essential) documentation. These include, but are not limited to: HREC 
correspondence, study intervention accountability logs, and curricula vitae of all personnel 
participating in the study. These files must be suitable for inspection at any time by the Sponsor, 
Clinical Research Associate, and/or applicable regulatory authorities. 
Protocol Amendments 
Neither the Investigator nor the Sponsor will modify or alter this protocol without the agreement 
of the other. All agreed protocol amendments will be clearly recorded on a protocol amendment 
form and will be signed and dated by the original protocol approving signatories. All protocol 
amendments will be submitted to the relevant HREC for approval before implementation, as 
required by local regulations. The only exception will be when the amendment is necessary to 
eliminate an immediate hazard to the study subjects. In this case, the necessary action will be 
taken first, with the relevant protocol amendment following shortly thereafter. 
Protocol Deviations 
Should any protocol deviation occur, it must be reported to the Clinical Research Associate 
(CRA) as soon as is reasonably practical. The deviation and the reason for its occurrence must be 
documented, reported to the relevant HREC (if required), and included in the study report. 
10.1.2 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate 
financial information as requested to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
study and for 1 year after completion of the study. 
10.1.3 
Informed Consent Process 
The Investigator(s) will ensure that the subject is given full and adequate oral and written 
information about the nature, purpose, possible risk, and benefit of the study. Subjects must also 
be notified that they are free to discontinue from the study at any time without prejudice. The 
subject should be given the opportunity to ask questions and allowed time to consider the 
information provided before voluntarily signing the written PICF. 
The subject’s signed and dated informed consent must be obtained before conducting any study 
procedures. The subjects will be informed of their rights to privacy but will be made aware that 
the study data will be submitted to the Sponsor and possibly to drug regulatory authorities for 
review and evaluation. They will be informed also that the CRA may inspect their medical 
records to verify the accuracy and completeness of the study records and results. 
The acquisition of informed consent should be documented in the subject’s medical records, as 
required by the Integrated Addendum to ICH E6(R1), GCP E6(R2), annotated with comments by 
the Australian Therapeutic Goods Administration (2018) and the NHMRC National Statement 
on Ethical Conduct in Human Research (2007, including current updates, 2018), and the PICF 

 
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will be signed and personally dated by the subject and by the person who conducted the informed 
consent discussion (not necessarily an Investigator). 
The Investigator must maintain the original, signed PICF. A copy of the signed PICF must be 
given to the subject or legal representative. The date that informed consent was signed will be 
recorded on the eCRF. 
10.1.4 
Data Protection 
• Subjects will be assigned a unique identifier by the Sponsor. Any subject records or 
datasets that are transferred to the Sponsor will contain the identifier only; subject 
names or any information which would make the subject identifiable will not be 
transferred. 
• The subject must be informed that his/her personal study-related data will be used by 
the Sponsor in accordance with local data protection law. The level of disclosure must 
also be explained to the subject who will be required to give consent for their data to 
be used as described in the informed consent 
• The subject must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate HREC members, and by inspectors from regulatory 
authorities. 
10.1.5 
Dissemination of Clinical Study Data 
• A CSR will be developed by the Sponsor at completion of data analysis. This report 
will be a clinical and statistical integrated report, according to the ICH E3 guidelines. 
• Sponsor will register the study and post study results regardless of outcome on a 
publicly accessible website (e.g., clinicaltrials.gov) in accordance with the applicable 
laws and regulations. 
10.1.6 
Data Quality Assurance 
• All subject data relating to the study will be recorded on printed or electronic eCRF 
unless transmitted to the Sponsor or designee electronically (e.g., laboratory data). 
The Investigator is responsible for verifying that data entries are accurate and correct 
by physically or electronically signing the eCRF. 
• The Investigator must maintain accurate documentation (source data) that supports 
the information entered in the eCRF. 
• The Investigator must permit study-related monitoring, audits, HREC review, and 
regulatory agency inspections and provide direct access to source data documents. 
• Monitoring details describing strategy (e.g., risk-based initiatives in operations and 
quality such as Risk Management and Mitigation Strategies and Analytical Risk-
Based Monitoring), methods, responsibilities, and requirements, including handling 
of noncompliance issues and monitoring techniques (central, remote, or on-site 
monitoring) are provided in the Monitoring Plan. 

 
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• The Sponsor or designee is responsible for the data management of this study 
including quality checking of the data. 
• The Sponsor assumes accountability for actions delegated to other individuals (e.g., 
Contract Research Organizations). 
• Study monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of subjects are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
• Records and documents, including signed ICFs, pertaining to the conduct of this 
study must be retained by the Investigator per ICH-GCP and local regulations or 
institutional policies. No records may be destroyed during the retention period 
without the written approval of the Sponsor. No records may be transferred to another 
location or party without written notification to the Sponsor. 
10.1.7 
Source Documents 
• Source documents provide evidence for the existence of the subject and substantiate 
the integrity of the data collected. Source documents are filed at the Investigator’s 
site. 
• Data reported on the eCRF or entered in the eCRF that are transcribed from source 
documents must be consistent with the source documents or the discrepancies must be 
explained. The Investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be available. 
• Source documents are original documents, data, and records from which the subject’s 
eCRF data are obtained. These include but are not limited to hospital records, clinical 
and office charts, laboratory and pharmacy records, diaries, microfiches, radiographs, 
and correspondence. 
10.1.8 
Study and Site Start and Closure 
The study start date is the date on which the clinical study will be open for recruitment of 
subjects. 
The first act of recruitment is the first site open and will be the study start date. 
The Sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor, else study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected 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: 

 
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• Failure of the Investigator to comply with the protocol, the requirements of the HREC 
or local health authorities, the Sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of subjects by the Investigator 
• Discontinuation of further study intervention development 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, the HREC(s), the regulatory authorities, and any contract research organization(s) 
used in the study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The Investigator shall promptly inform the subject(s) and should assure 
appropriate subject therapy and/or follow-up. 
10.1.9 
Publication Policy 
The publication policy for this study is located within the Clinical Study Agreement with the 
Investigator and/or Institution. 
 

 
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10.2 
APPENDIX 2: CLINICAL LABORATORY TESTS 
• The clinical laboratory tests detailed in Table 5 will be performed by a central 
laboratory at timing/frequency detailed in the SoA (Section 1.3) 
• Additional tests may be performed at any time during the study as determined 
necessary by the Investigator or required by local regulations. 
• Investigators must document their review of each laboratory safety report 
Table 5: 
Clinical Safety Laboratory Tests 
Hematology 
 
White blood cell count (WBC) with 
differential (neutrophils, lymphocytes, 
monocytes, eosinophils, basophils – 
absolute and %) 
Red blood cell (RBC) 
RBC Indices: 
MCV, MCH, %Reticulocytes 
Haemoglobin 
Haematocrit 
Platelet count 
 
Clinical Chemistriesa 
 
Electrolytes: Sodium, Potassium, CO2 or bicarbonate, Chloride, Calcium, Magnesium, 
Phosphorus, 
Liver function: Alkaline Phosphatase, alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), Total Bilirubin 
Renal function: Blood Urea Nitrogen, Creatinine, Creatine Kinase, calculated Creatinine 
Clearance Cockcroft-Gault 
Other: Albumin, lactate dehydrogenase (LDH), non-fasting Glucose, uric acid, lactate 
dehydrogenase, total protein, total cholesterol, and triglycerides 
Urinalysis 
 
Basic Urinalysis (dipstick, including 
macroscopic 
appearance, bilirubin, blood, colour, 
glucose, ketones, leukocyte esterase, nitrite, 
pH, protein, specific gravity, urobilinogen;  
Full urinalysis (dipstick plus microscopic 
evaluation) to be performed only at the 
Screening and End of Study visits). A reflex 
microscopic urinalysis should be performed if 
the result of the urinalysis is abnormal or at the 
discretion of the PI or delegate. 
Other Study-Specific Laboratory Assessments 
Serum and urine human chorionic 
gonadotropin (hCG) pregnancy test 
Syphilis screening test (rapid plasma 
regain) 
Serology 
HIV antibody, 
hepatitis B surface antigen (HBsAg), 
hepatitis C virus antibody or HCV RNA 
(qualitative) 

 
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10.3 
APPENDIX 3: AES AND SAES: DEFINITIONS AND PROCEDURES FOR RECORDING, 
EVALUATING, FOLLOW-UP, AND REPORTING 
10.3.1 
Definition of AE 
AE Definition 
• An AE is any untoward medical occurrence in a subject or clinical study subject, 
temporally associated with the use of study intervention, whether or not considered 
related to the study intervention. 
• NOTE: An AE can therefore be any unfavourable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of study intervention. 
 
Events Meeting the AE Definition 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the Investigator (i.e., not 
related to progression of underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 
• “Lack of efficacy” or “failure of expected pharmacological action” per se will not 
be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting from 
lack of efficacy will be reported as AE or SAE if they fulfil the definition of an AE 
or SAE. 
 

 
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Events NOT Meeting the AE Definition 
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
Investigator to be more severe than expected for the subject’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
subject’s condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
10.3.2 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to 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. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
• In general, hospitalization signifies that the subject has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious. 
• Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
d. Results in persistent disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 

 
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• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Other situations (Medically important): 
• Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the subject or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious. 
• Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse. 
10.3.3 
Recording and Follow-Up of AE and/or SAE 
AE and SAE Recording 
• When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event. 
• The Investigator will then record all relevant AE/SAE information in the eCRF 
within 24 hours of Investigator/site awareness of the event. 
• It is not acceptable for the Investigator to send photocopies of the subject’s medical 
records to the Sponsor in lieu of completion of the AE/SAE eCRF page. 
• There may be instances when copies of medical records for certain cases are 
requested by the Sponsor. In this case, all subject identifiers, except for the subject 
number, will be redacted on the copies of the medical records before submission to 
the Sponsor. 
• The Investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE. 

 
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Assessment of Intensity 
AE severity will be evaluated by the Investigator in accordance with the NCI CTCAE v5.01. 
For AEs that are not adequately addressed in the NCI CTCAE, the Investigator should classify 
the intensity of the AE using the following guidelines: 
• Grade 1: Mild: Aware of sign or symptom, but easily tolerated; no intervention needed 
• Grade 2: Moderate: Discomfort enough to cause interference with usual activity, 
minimal non-invasive intervention indicated (e.g., short course of antibiotics) 
• Grade 3: Severe: Medically significant but not immediately life-threatening; 
incapacitation with inability to work or do usual activity 
• Grade 4: Life-threatening: Refers to an event in which the subject was at risk of death 
at the time of the event, as judged by the Investigator; urgent/emergent intervention 
indicated. This category should not be used for an event that hypothetically might have 
caused death if it were more severe. 
• Grade 5: Fatal outcome. 
It will be left to the Investigator’s clinical judgment to determine whether an AE is of 
sufficient severity to require the subject’s removal from treatment or from the study. A subject 
may also voluntarily withdraw consent from treatment due to what she/he perceives as an 
intolerable AE. If either of these situations arises, the subject should be strongly encouraged to 
undergo an end-of-study assessment and be under medical supervision until symptoms cease 
or the condition becomes stable. An event is defined as ‘serious’ when it meets at least 1 of the 
predefined outcomes as described in the definition of an SAE, NOT when it is rated as severe. 
 
Assessment of Causality 
• The Investigator is obligated to assess the relationship between study intervention and 
each occurrence of each AE/SAE. 
• A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out. 
• The Investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• The Investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
 
1 Please refer to the CTCAE v5 published on November 2017 at: 
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• For each AE/SAE, the Investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred, and the Investigator has 
minimal information to include in the initial report to the Sponsor. However, it is 
important that the Investigator always make an assessment of causality for every event 
before the initial transmission of the SAE data to the Sponsor. 
• The Investigator may change his/her opinion of causality considering follow-up 
information and send an SAE follow-up report with the updated causality assessment. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
Causality Categories: 
• Related: An event is considered related if there is a reasonable possibility of causal 
association between the study intervention and the event. This means there is evidence 
to suggest a causal relationship between the study intervention and the AE. The AE 
follows a reasonable temporal sequence from the time of study intervention 
administration and follows a known response to the study intervention and cannot be 
reasonably explained by other factors such as the subject's clinical state or other 
therapeutic interventions, or concomitant drugs administered to the subject. 
• Not related: The available evidence support that the event is related to other factors 
such as the subject’s clinical state, therapeutic interventions or concomitant drugs 
administered to the subject. 
 
Follow-up of AEs and SAEs 
• The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
Sponsor to elucidate the nature and/or causality of the AE or SAE as fully as 
possible. This may include additional laboratory tests or investigations, 
histopathological examinations, or consultation with other health care 
professionals. 
• If a subject die during participation in the study or during a recognized follow-up 
period, the Investigator will provide the Sponsor with a copy of any post-mortem 
findings including histopathology, if available. 
• New or updated information will be recorded in the originally completed eCRF. 
• The Investigator will submit any updated SAE data to the Sponsor within 24 hours 
of receipt of the information. 

 
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10.3.4 
Reporting of SAEs 
SAE Reporting to the Sponsor via an Electronic Data Collection Tool 
• The primary mechanism for reporting an SAE to the Sponsor will be the electronic 
data collection tool. 
• If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool to report the event within 24 hours. 
• The site will enter the SAE data into the electronic system as soon as it becomes 
available and within 24 hours of Investigator/site awareness. 
• After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• If a site receives a report of a new SAE from a study subject or receives updated 
data on a previously reported SAE after the electronic data collection tool has been 
taken off-line, then the site can report this information on a paper SAE form or to 
the Sponsor’s Medical Monitor by telephone. 
• Contacts for SAE reporting is provided in the SAE form. 
 
 

 
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10.4 
APPENDIX 4: CONTRACEPTIVE GUIDANCE AND COLLECTION OF PREGNANCY 
INFORMATION 
10.4.1 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP: 
2. Premenarchal 
3. Premenopausal female with 1 of the following: 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
For individuals with permanent infertility due to a medical cause other than the above, (e.g., 
Mullerian agenesis, androgen insensitivity), Investigator discretion should be applied to 
determining study entry. 
Note: Documentation can come from the site personnel’s review of the subject’s medical 
records, medical examination, or medical history interview. 
Postmenopausal female 
• A postmenopausal state is defined as having had no menses for 1 year without an 
alternative medical cause. 
− 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 (HRT). However, in the absence of 
1 year of amenorrhea, confirmation with more than one FSH measurement is 
required. 
• Females on HRT and whose menopausal status is in doubt will be required to use one 
of the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrolment. 
10.4.2 
Contraception Guidance 
Male Subjects 
Male subjects are eligible to participate if they agree to the following from informed consent, 
during the treatment period and for 90 days after the last dose of study intervention: 
• Refrain from donating sperm 

 
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PLUS, either: 
• Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long term and persistent basis) and agree to remain abstinent 
OR 
• Must agree to use contraception/barrier as detailed below 
− Agree to use a male condom 
Female Subjects 
• A female subject is eligible to participate if she is not pregnant or breastfeeding, and 
at least one of the following conditions applies: 
− Is not a woman of childbearing potential (WOCBP) 
OR 
− Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of < 1% per year), preferably with low user dependency (see table 
below), at least 28 days prior to 1st screening visit, during the intervention period, 
and for 60 days after the last dose of study intervention, and agrees not to donate 
eggs (ova, oocytes) for the purpose of reproduction during this period. The 
Investigator should evaluate the effectiveness of the contraceptive method in 
relationship to the first dose of study intervention. 
− A WOCBP must have negative serum pregnancy test (minimum sensitivity 
25 IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 
hours prior to receiving the first administration of study intervention and a 
negative urine pregnancy test on Baseline before first administration of study 
intervention. If the urine test is positive or cannot be confirmed as negative, a 
serum pregnancy test is required, and results must be negative. 
− If a urine test cannot be confirmed as negative (e.g., an ambiguous result), a serum 
pregnancy test is required, and results must be negative. In such cases, the subject 
must be excluded from participation if the serum pregnancy result is positive. 
Contraceptive use by men or women should be consistent with local regulations regarding the 
use of contraceptive methods for those participating in clinical studies. 

 
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Table 6: 
Contraception Methods Acceptable for this Study 
Highly Effective Methodsa That Have Low User Dependency  
• Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation 
• Intrauterine device (IUD) 
• ParaGurad Intrauterine hormone-releasing system (IUS) (non-hormonal)b 
• Bilateral tubal occlusion 
• Vasectomized partner 
(Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective method 
of contraception should be used. Spermatogenesis cycle is approximately 90 days.) 
Highly Effective Methodsa That Are User Dependent  
• Progestogen-only hormone contraception associated with inhibition of ovulationb 
− oral 
− injectable 
• Sexual abstinence 
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study 
intervention. The reliability of sexual abstinence needs to be evaluated in relation to the 
duration of the study and the preferred and usual lifestyle of the subject.) 
Other Methods 
• Diaphragm (must be used with another contraceptive method) 
a Failure rate of < 1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
Note: Periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception for this 
study. 
10.4.3 
Collection of Pregnancy Information 
Male subjects with partners who become pregnant 
• The Investigator will attempt to collect pregnancy information on any male subject’s 
female partner who becomes pregnant while the male subject is in this study. This 
applies only to male subjects who receive study intervention. 
• After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the Investigator will record pregnancy information on the appropriate 

 
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form and submit it to the Sponsor within 24 hours of learning of the partner’s 
pregnancy. The female partner will also be followed to determine the outcome of the 
pregnancy. Information on the status of the mother and child will be forwarded to the 
Sponsor. Generally, the follow-up will be no longer than 6 to 8 weeks following the 
estimated delivery date. Any termination of the pregnancy will be reported regardless 
of foetal status (presence or absence of anomalies) or indication for the procedure. 
Female Subjects who become pregnant 
• The Investigator will collect pregnancy information on any female subject who 
becomes pregnant while participating in this study. The initial information will be 
recorded on the appropriate form and submitted to the Sponsor within 24 hours of 
learning of a subject's pregnancy. 
• The subject will be followed to determine the outcome of the pregnancy. The 
Investigator will collect follow-up information on the subject and the neonate, and the 
information will be forwarded to the Sponsor. Generally, follow-up will not be 
required for longer than 6 to 8 weeks beyond the estimated delivery date. Any 
termination of pregnancy will be reported, regardless of foetal status (presence or 
absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an SAE, any pregnancy complication 
or elective termination of a pregnancy for medical reasons will be reported to the 
Sponsor as an SAE. 
• A spontaneous abortion (occurring at <22 weeks gestational age) or still birth 
(occurring at >22 weeks gestational age) is always considered to be an SAE and will 
be reported as such. 
• Any post-study pregnancy related SAE considered related to the study intervention by 
the Investigator will be reported to the Sponsor. While the Investigator is not 
obligated to actively seek this information in former study subjects, he or she may 
learn of an SAE through spontaneous reporting. 
• Any female subject who becomes pregnant while participating in the study will 
discontinue study intervention or be withdrawn from the study. 
 
 

 
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10.5 
APPENDIX 5: SUMMARY OF RESPONSE EVALUATION CRITERIA IN SOLID TUMOURS 
(RECIST) V1.1 
10.5.1 
RECIST v1.1 
Disease response will be evaluated using the RECIST v1.1 by the Investigator at timepoints 
specified in the SoA. The following summarizes the process for selecting baseline measurable 
lesions and deriving the appropriate response at subsequent imaging time points. For specific 
details related to the response criteria please refer to the published RECIST v1.1 (Eisenhauer, 
2009). 
Evaluation of Tumour Burden at Subsequent Assessments 
Please refer to the SoA for the timing of subsequent imaging assessments. 
Target Lesions: 
Target lesions are measured at every subsequent assessment and an overall SOD is calculated. 
Target lesions are assessed as Complete Response (CR), Partial Response (PR), Stable Disease 
(SD), Progressive Disease (PD), or Not All Evaluated (NAE) at every time point based on the 
calculated SOD. 
Target Assessment 
Evaluation Definition 
Complete Response (CR) 
CR is declared if ALL of the following are true for target lesions: 
• The disappearance of all non-nodal target lesions 
• Any pathological lymph nodes must have a reduction in 
short axis to <10 mm. 
Partial Response (PR) 
PR is declared if there is a decrease of at least 30% in the SOD of 
target lesions compared to the baseline SOD of target lesions. 
Progressive Disease (PD) 
PD is declared if ANY of the following are true for target lesions: 
• 
SOD of all target lesions increases at least 20% compared to the 
smallest SOD recorded from any prior assessment 
NOTE: In addition to the relative increase at least 20%, the sum 
must also demonstrate an absolute increase of at least 5 mm. 
OR 
• 
The appearance of one or more new lesions. 
Stable Disease (SD) 
SD is declared if target lesion assessment does not meet criteria for 
PR, PD, or CR. 
 

 
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Non-Target Lesions: 
While some non-target lesions may actually be measurable, they need not be measured and 
instead should be assessed qualitatively at subsequent assessments. Non-target lesions are 
assessed as CR, PD, non-CR/non-PD (NCNP), or NAE at every time point. 
Non-Target Assessment 
Evaluation Definition 
Complete Response (CR) 
CR is declared if ALL of the following are true for non-target lesions: 
• 
Disappearance of all non-target lesions and normalization of 
tumour marker level. 
• 
All lymph nodes must be non-pathological in size (<10 mm 
short axis). 
Non-CR/Non-PD (NCNP) 
NCNP is declared when persistence of one or more non-target 
lesion(s) and/or the maintenance of tumour marker level above the 
normal limits is observed. 
Progressive Disease (PD) 
PD is declared if ANY of the following are true for non-target lesions: 
• 
Unequivocal Progression of existing non-target lesions. 
NOTE: Unequivocal Progression of non-target disease is 
defined as an overall level of substantial worsening in non-
target disease such that, even in presence of SD or PR in target 
disease, the overall tumour burden has increased sufficiently to 
merit discontinuation of therapy. A modest increase in the size 
of one or more non-target lesion(s) is usually not sufficient to 
quality for unequivocal progression. The designation of overall 
progression solely on the basis of change in non-target disease 
in the face of SD or PR of target disease should therefore be 
extremely rare. 
OR 
• The appearance of one or more new lesions. 
 
New Lesions: 
The determination of new lesions should be unequivocal and not be attributable to differences in 
the scanning technique, change in modality, or findings thought to represent something other 
than tumour. This is particularly important when the subject’s target lesions show PR or CR. 
A lesion identified at a subsequent time point in an anatomical location that was not scanned at 
baseline is considered a new lesion and will indicate disease progression. This underscores the 
importance of scanning all anatomical locations that are suspected to contribute to disease 
burden at baseline. 
Bone metastases: 
Evaluation of response in subjects with bone-only disease will be performed by MRI (preferred 
modality) per modified MDA criteria (Table 7). CT scans should only be performed when MRI 
is contraindicated (cases of bypass for example). 

 
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Table 7: 
Modified MD Anderson (MDA) Criteria for Bone Metastases+ 
Response 
Category 
Criteria 
Complete 
Response 
Normalization of Signal intensity on MRI 
Complete sclerotic fill-in of lytic lesions or normalization of bone density on CT* 
Partial 
Response 
Osteoblastic flare – Interval visualization of lesions with sclerotic rims or new 
sclerotic lesions in the setting of other signs of PR and absence of progressive bony 
disease 
≥50% decrease in measurable lesions on MRI  
≥50% decrease in measurable lesions or ≥50% subjective decrease on ill-defined 
lesions on CT* 
Progressive 
disease 
≥25% increase in size of measurable lesions on MRI 
≥25% increase in size of measurable lesions or subjective increase in the size of 
ill-defined lesions on CT* 
New bone metastasis 
Stable 
disease 
No change 
<25% increase or <50% decrease in size of measurable lesions 
<25% subjective increase or <50% subjective decrease in size of ill-defined lesions 
No new bone metastasis 
*CT only to be performed if MRI is contraindicated 
+Measurements are based on the sum of a perpendicular, bidimensional measurement of the greatest diameters of 
each individual lesion 
Source: (Costelloe, 2010) 
Table 8: 
Overall Time Point Response Assignment at Subsequent Assessments 
Once the Target-Lesion, Non-Target Lesion, and New Lesion Assessments have been completed 
for a subsequent imaging assessment, an Overall Time Point Response may be assigned. 
Target Lesion 
Assessment 
Non-Target Lesion 
Assessment 
New Lesion 
Assessment 
Overall Time Point 
Response 
CR 
CR 
No 
CR 
CR 
NCNP 
No 
PR 
CR 
NAE 
No 
PR 
PR 
NCNP or NAE 
No 
PR 
SD 
NCNP or NAE 
No 
SD 
NAE 
NCNP 
No 
NE 
PD 
Any 
Yes or No 
PD 
Any 
PD 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
CR - Complete Response, PR - Partial Response, SD - Stable Disease, PD - Progressive Disease, 
NCNP - Non-CR/Non-PD, NAE - Not All Evaluated, NE - Not Evaluable  
 

 
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10.5.2 
Radiographic Imaging as Basis for Methods of Measurement 
• Computed tomography (CT) and Magnetic resonance imaging (MRI): CT and MRI 
are the best currently available and reproducible methods to measure target lesions 
selected for response assessment. Conventional CT and MRI should be performed 
with cuts of 10 mm or less in slice thickness contiguously. Spiral CT should be 
performed using a 5 mm contiguous reconstruction algorithm. This applies to tumours 
of the chest, abdomen, and pelvis. Head and neck tumours and those of extremities 
usually require specific protocols. See RECIST v1.1. guidelines for additional 
specifications on CT and MRI measurements. 
• Chest X-ray: Chest CT is preferred over chest x-ray; particularly when progression is 
an important endpoint, since CT is more sensitive. 
• Ultrasound: Ultrasound is not useful in assessment of lesion size and should not be 
used as a method of measurement. Ultrasound examinations cannot be reproduced in 
their entirety for independent review at a later date and because they are operator 
dependent, it cannot be guaranteed that the same technique and measurements will be 
taken from one assessment to the next. If new lesions are identified by ultrasound in 
the course of the study, confirmation by CT or MRI is advised. If there is a concern 
about radiation exposure at CT, MRI may be used instead of CT in selected instances. 
• Endoscopy and Laparoscopy: The utilization of endoscopy and laparoscopy for 
objective tumour evaluation is not advised. 
• Tumour Markers: Tumour markers alone cannot be used to assess response. If 
markers are initially above the upper normal limit, they must normalize for a subject 
to be considered in complete clinical response when all lesions have disappeared. 
• Cytology and Histology: These techniques can be used to differentiate between PR 
and CR in rare cases (e.g., after treatment to differentiate between residual benign 
lesions and residual malignant lesions in tumour types such as germ cell tumours). 
The same imaging modality should be used throughout the study for a given subject. 
Details concerning all of the above methods of measurement can be obtained in the RECIST 
v1.1. guidelines. 
 
 

 
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10.6 
APPENDIX 6:  MODIFIED RECIST V1.1 FOR IMMUNE-BASED THERAPEUTICS 
Immunotherapeutics may result in infiltration of immune cells leading to transient increase in the 
measured size of a target lesion, or undetectable lesions becoming detectable. The criteria are 
identical to those of RECIST v1.1 in many respects but have been adapted to account for 
instances where an increase in tumor burden, or the appearance of new lesions, does not reflect 
true tumor progression but rather a favorable inflammation of the tumor. 
Unlike RECIST v1.1, iRECIST requires the confirmation of progression on a subsequent scan 
and uses the terms iUPD (immune unconfirmed progression) and iCPD (immune confirmed 
progression). Confirmatory scans should be performed at least 4 weeks, but no longer than 
8 weeks after iUPD. 
For target lesions, iCR, iPR, and iSD can all be assigned after iUPD has been documented, as 
long as iCPD was not confirmed (Table 9). iUPD is defined by RECIST v1.1 criteria for 
progressive disease; iUPD can be assigned multiple times as long as iCPD is not confirmed at the 
next assessment. Progression is confirmed in the target lesion category if the next imaging 
assessment after iUPD (4–8 weeks later) confirms a further increase in sum of measures of target 
disease from iUPD, with an increase of at least 5 mm. However, the criteria for iCPD (after 
iUPD) are not considered to have been met if CR, PR, or SD criteria (compared with baseline 
and as defined by RECIST v1.1) are met at the next assessment after iUPD. The status is reset 
(unlike RECIST v1.1, in which any progression precludes later CR, PR, or SD). iCR, iPR, or iSD 
should then be assigned; and if no change is detected, then the timepoint response is iUPD. 
The assessment of non-target lesions at each timepoint follows similar principles. iUPD (but not 
iCPD) can have been documented before iCR or when the criteria for neither CR nor PD have 
been met (referred to as non-iCPD/non-iUPD) and can be assigned several times, as long as 
iCPD was not confirmed. iUPD is defined by RECIST v1.1 criteria; however, iUPD can be 
assigned multiple times as long as iCPD is not confirmed at the next assessment. Progressive 
disease in the non-target lesion category is confirmed if subsequent imaging, done 4–8 weeks 
after iUPD, shows a further increase from iUPD. The criteria for iCPD are not judged to have 
been met if RECIST v1.1 criteria for complete response or non-iCR/non-iUPD are met after a 
previous iUPD. The status is reset (unlike RECIST v1.1) and iCR, or non-iCR/non-iUPD is 
assigned; if no change is detected, the timepoint response is iUPD. 
iCPD is confirmed if further increase in tumour burden, compared to the last assessment, is seen 
as evidenced by one or more of the following: 
• Continued increase in tumour burden (from iUPD) where RECIST v1.1 definitions 
of progression had been met (from nadir) in target, non-target disease or new 
lesions 
− Progression in target disease worsens with an increase of at least 5 mm in the 
absolute value of the sum 
− Continued unequivocal progression in non-target disease with an increase in 
tumour burden 
− Increase in size of previously identified new lesion (s) (an increase of at least 
5 mm in the absolute value of the sum of those considered to be target new 

 
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lesions) or additional new lesions. 
• RECIST v1.1 criteria are met in lesion (target or non-target) where progression was 
not previously identified, including the appearance of additional new lesions. 
If iUPD is not confirmed at the next assessment, then the appropriate response will be assigned 
(iUPD if the criteria are still met, but no worsening, or iSD, iPR or iCR if those criteria are met 
compared to baseline). The prior documentation of iUPD does not preclude assigning iCR, iPR, 
or iSD in subsequent time-point assessments or as immune overall response (iOR) providing that 
iCPD is not documented at the next assessment after iUPD. 
The event date to be used for calculation of progression-free survival (iPFS) should be the first 
date at which progression criteria are met (i.e., the date of iUPD) provided that iCPD is 
confirmed at the next assessment. If iUPD occurs, but is disregarded because of later iSD, iPR, 
or iCR, that iUPD date should not be used as the progression event date. 
Table 9 
 
iRECIST Time Point iResponse 
Target 
Lesions*  
Non-Target 
Lesions* 
New 
Lesions* 
Time Point Response 
No 
prior 
iUPD**  
Prior iUPD**; ***  
iCR  
iCR  
No  
iCR  
iCR  
iCR  
Non-iCR/Non-iUPD  No  
iPR  
iPR  
iPR  
Non-iCR/Non-iUPD  No  
iPR  
iPR  
iSD  
Non-iCR/Non-iUPD  No  
iSD  
iSD  
iUPD with no 
change OR 
decrease from 
last time point  
iUPD with no 
change OR decrease 
from last TP  
Yes  
NA  
New lesions (NL) confirms iCPD if NLs were 
previously identified and increase in size (≥5 mm 
in sum of measure (SOM) for new lesion, target 
(NLT) or any increase for new lesion, non-target; 
NLNT) or number. If no change in NLs (size or 
number) from last time point, remains iUPD  
iSD  
iUPD  
No  
iUPD  
Remains iUPD unless iCPD confirmed based in 
further increase in size of non-target disease (need 
not meet RECIST v1.1 criteria for unequivocal 
PD)  
iUPD  
Non-iCR/Non-iUPD  No  
iUPD  
Remains iUPD unless iCPD confirmed based on: 
o further increase in SOM of at least 5 mm, 
otherwise remains iUPD  
iUPD  
iUPD  
No  
iUPD  
Remains iUPD unless iCPD confirmed based on 
further increase in: 
o previously identified T lesion iUPD sum of 
measure ≥5 mm and / or 
o NT lesion iUPD (prior assessment - need not be 
unequivocal PD)  
iUPD  
iUPD  
Yes  
iUPD  
Remains iUPD unless iCPD confirmed based on 
further increase in: 
• 
previously 
identified 
Target 
lesion iUPD ≥5 mm and / or 
• 
previously identified non-target 
lesion iUPD (need not be 

 
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unequivocal) and /or 
• 
size or number of new lesions 
previously identified 
Non-iUPD/PD  Non-iUPD/PD  
Yes  
iUPD  
Remains iUPD unless iCPD confirmed based on 
o increase in size or number of new lesions 
previously identified  
TP = time-point; NT = non-target, T = target; NL = new lesions; iUPD = unconfirmed immune PD; iCPD = 
confirmed immune PD; SOM = sum of measures. iCR – immune complete response; iPR – immune partial 
response; iSD – immune stable disease 
* Using RECIST v1.1 principles. If no PSPD occurs, RECIST v1.1 and iRECIST categories for CR, PR and SD 
would be the same. 
** in any lesion category. 
*** previously identified in assessment immediately prior to this time point.  
Source: (Seymour, 2017a) 
 

 
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10.7 
APPENDIX 7: CRS TOXICITY TREATMENT GUIDELINES 
Note these as guidelines may require modification based on clinical circumstances of each 
subject. The investigator should consider both best outcome for the subject and institutional 
standard of care treatment protocols. As such failure to exactly follow these guidelines is not a 
protocol deviation or violation as follows: 
Cytokine Release Syndrome Grading Assessment (Lee, 
2019) 
Corticosteroids 
Grade 1: Symptoms are not life-threatening and require 
symptomatic treatment only (fever, nausea, fatigue, headache, 
myalgias, malaise)  
• 
N/A 
Grade 2: Symptoms require and respond to moderate 
intervention: 
• 
Oxygen requirement <40% FiO2 
OR 
• 
Hypotension responsive to IV fluids or low dose of one 
vasopressor 
OR 
• 
Grade 2 organ toxicity*  
• 
Vigilant supportive care with careful 
monitoring of cardiac and other organ 
function  
Grade 2: As above but with extensive co-morbidities or older 
age. 
OR 
Grade 3: Symptoms require and respond to aggressive 
intervention: 
• 
Extensive co-morbidities or older age  
• 
Oxygen requirement ≥40% FiO2 
OR 
• 
Hypotension requiring high-dose or multiple 
vasopressors 
OR 
• 
• Grade 3 organ toxicity* or Grade 4 transaminitis  
• 
Administer methylprednisolone 
1 mg/kg IV twice daily or equivalent 
dexamethasone (e.g., 10 mg IV every 6 
hours). Continue corticosteroids use 
until the event is Grade 1 or less, then 
taper over 3 days. 
• 
If no improvement, within 24 hours, 
consider starting tocilizumab or 
manage as Grade 4 (below)  
Grade 4: Life-threatening symptoms: 
• 
Requirement for ventilator support 
OR 
• 
Grade 4 organ toxicity* (excluding transaminitis)  
• 
Administer methylprednisolone 
1000 mg IV per day for 3 days; if 
improves, then manage as above. 
• 
Consider alternate 
immunosuppressants if no 
improvement or if condition worsens. 
Source: (Lee, 2019) (EMA, 2018) 
 

 
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10.8 
APPENDIX 8: TLS TOXICITY MANAGEMENT 
Note these are guidelines that might require modification based on clinical circumstances 
of each subject and consider institutional standard of care treatment protocols, and 
failure to exactly follow these guidelines is not a protocol deviation or violation as follows: 
Tumor lysis syndrome (TLS) is an oncology emergency that occurs as a result of rapid tumor cell 
breakdown and the consequent release of massive amounts of intracellular contents, including 
potassium, phosphate, and uric acid, into the systemic circulation. These metabolic disturbances 
lead to life-threatening conditions and may cause sudden death if not treated. TLS commonly 
occurs following initiation of cytotoxic treatment in patients with high-grade lymphomas or 
acute lymphoblastic leukemia. Spontaneous cases involving both solid and hematologic tumors 
have also been reported. Rarely, TLS occurs following treatment with irradiation, 
corticosteroids, hormonal therapy, or biologic therapy. It is necessary to identify subjects at risk 
for TLS early in order to initiate preventive measures. In the event that preventive measures fail, 
the clinical parameters and signs of TLS must be understood and recognized so that treatment 
can begin as soon as possible, as this condition is a significant cause of morbidity and mortality. 
When tumor cells are rapidly broken down and their contents released into the extracellular 
space, the released ions and compounds can cause metabolic disturbances too great to be 
neutralized by the body's normal mechanisms. The syndrome characterized by these metabolic 
derangements is known as TLS. TLS can cause life-threatening conditions and even death unless 
appropriately and immediately treated. 
The Cairo-Bishop definition provided specific laboratory criteria for the diagnosis of TLS, as 
well as a grading system for describing the degree of severity of TLS (Cairo, 2010). Laboratory 
TLS is defined as any two (or more) of the following abnormalities: 
• Serum uric acid level ≥ 8 mg/dL, or 25% increase from baseline. 
• Serum potassium level ≥ 6 mmol/L, or 25% increase from baseline. 
• Serum phosphate level ≥ 6.5 mg/dL in children and ≥ 4.5 mg/dL in adults, or 25% 
increase from baseline. 
• Serum calcium level ≤ 7 mg/dL, or 25% decrease from baseline. 
All these abnormalities must occur within 7 days after the dosing with SUPLEXA. 
Table 10 provides recommendation for prevention and treatment of TLS according to the 
subject’s risk level as shown in Figure 6. Investigator should consider institution standard of care 
treatment protocols. Subjects will likely need to be aggressively hydrated with IV fluids. The 
target diuresis is at least 100 to 200 mL/hour (similar to the prophylaxis rate). Loop diuretics or 
mannitol may be used in conjunction with aggressive fluid-loading to promote aggressive 
diuresis. Furosemide can be used for this purpose in dosages of 20 to 100 mg IV every 4 to 8 
hours or as an IV infusion of 10 to 20 mg/hour. Allopurinol, urate oxidase, and possibly urinary 
alkalinization all have a role in management. Ultimately, dialysis may also be needed, especially 
if a subject exhibits severe or refractory acute renal failure and/or symptoms from the metabolic 
derangements. 
 

 
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Figure 6: TLS risk assessment of solid tumours, myelomas and chronic leukaemias 
 
Source: (Cairo, 2010) 
Abbreviation: LRD, low risk disease; IRD, intermediate risk disease 

 
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Table 10: Recommendation for Prevention and Treatment of Tumour Lysis Syndrome 
Risk Level 
Low-risk disease 
Intermediate-risk disease 
High-risk disease 
Diagnostic 
measures 
• 
No specific 
measures 
• 
Daily monitoring of 
laboratory abnormalities 
before and during the first 
7 days of anticancer 
therapy 
• 
At least twice daily 
monitoring of laboratory 
abnormalities before and 
during the first 7 days of 
anticancer therapy 
Preventive 
measures 
• 
Moderate 
hydration is 
recommended 
• 
Vigorous hydration 
• 
Keep urinary output >100 
mL/h 
• 
Treatment with allopurinol 
or febuxostat should be 
started at least 24 hours 
before initiation of 
anticancer therapy and 
should be continued till 
normalization of uric acid 
levels and signs of large 
tumour burden are absent 
• 
vigorous hydration 
• 
Keep urinary output 
>100 mL/h  
• 
Single dose 6 mg of 
rasburicase. Repeat 
doses, as necessary. in 
case of contraindication 
treatment with 
febuxostat 
Treatment of 
established 
tumour lysis 
syndrome 
• 
Admission to intensive care unit with continuous cardiac monitoring and 
monitoring of laboratory abnormalities every 4–6 hours 
• 
early nephrology consultation to estimate the indications for renal replacement 
therapy 
• 
Correction of electrolyte abnormalities 
• 
vigorous hydration, keep urinary output >100 mL/h 
• 
Single dose 6 mg of rasburicase. Repeat doses as necessary. In case of 
contraindication, treatment with febuxostat 
Source: (Alakel, 2017) 
 

 
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10.9 
APPENDIX 9: GUIDANCE TO ADDRESS GLOBAL HEALTH EMERGENCIES AND POTENTIAL 
IMPACT ON THE CLINICAL STUDY 
As of March 12, 2020, a coronavirus disease 2019 (COVID-19) pandemic has been declared by the 
World Health Organization, leading to implementation of extensive measures by healthcare systems 
globally to limit viral spread, with potential impact on conduct of clinical studies (because 
subjects/healthcare workers are in self-isolation/quarantine, there is limited access to public places, including 
hospitals, and health care professionals are committed to critical tasks). 
Based on guidelines issued by global regulatory authorities ((Health Canada, 03 April 2020; MHRA, 22 
April 2020; Australian Government, 2020; EMA, April 2020; FDA, March 2020)), the actions listed below 
are being implemented in this protocol to address potential disruptions to study conduct secondary to 
COVID-19 infection or control measures. These actions are to assure the safety of study subjects, 
maintain compliance with good GCP, and minimize the risks to study integrity. 
Informed Consent 
• If written consent by the study subject is not possible (for example because of physical isolation due 
to COVID-19 infection), consent could be given orally by the study subject. 
• Study subjects and the person obtaining consent could sign and date separate informed consent 
forms 
• In case a written informed consent cannot be obtained at the clinical site, electronic informed 
consent can be obtained remotely. Alternatively, the consent form may be sent to the subject or the 
subject’s legally authorized representative by facsimile or e-mail, and the consent interview may 
then be conducted by telephone when the subject or subject’s legally authorized representative can 
read the consent form during the discussion. 
• If re-consent is necessary for the implementation of new urgent changes in study conduct (mainly 
expected for reasons related to COVID-19 or important safety issues for other trials), alternative 
ways of obtaining may include contacting the study subject via phone or video-calls and obtaining 
oral consents, to be documented in the study subjects’ medical records, supplemented with e-mail 
confirmation. 
• The informed consent procedure to remain compliant with the study protocol as well as local 
regulatory requirements. All relevant records should be archived in the Investigator's site master file. 
A correctly signed and dated informed consent form should be obtained from the study subjects 
later, as soon as possible. 
Study Visits and Procedures 
• COVID-19 screening procedures that may be mandated by the health care system in which a clinical 
study is being conducted do not need to be reported as an amendment to the protocol even if done 
during clinical study visits. The Investigator in consultation with the Sponsor will decide if it is in 
the best interest of COVID-positive subjects to remain in the study. 
• In the case of missed visits due to COVID-19 (or other public health emergencies) related reasons: 
− The site should make every effort to contact the study subject to confirm and document the 
reason for the missed visit, and at minimum evaluate AEs/SAEs, and concomitant 
medications in order to assess subject safety. 

 
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− The study subject should continue to collect the daily diary responses on the diary. 
• To maintain the integrity of the study, if study subjects cannot access a clinical study site, alternative 
methods of collecting study procedures may be considered where possible and in certain situations, 
with Sponsor approval: 
− A local laboratory may be used to collect laboratory samples as required by the protocol. 
Local analysis can be used for safety decisions. In addition, local laboratory can be used 
for study endpoints if samples drawn at the local laboratory cannot be shipped to the 
central laboratory. If a local laboratory is used, applicable lab ranges and laboratory 
certification should be provided to the Sponsor. 
− According to site business continuity plans, home visits may be used to collect laboratory 
samples and assessments as required by the protocol. 
− In cases where a subject is continuing to receive study intervention but COVID-19 
pandemic-related circumstances preclude a visit to the investigative site, remote visits (e.g., 
virtual visits by telemedicine or phone contact) will be allowed for relevant study 
procedures while maintaining subject’s privacy, as would be done for a clinic visit. 
− Alternate imaging centres may be used; this depends on whether the protocol-specified 
procedures are related to eligibility criteria, safety evaluations, or endpoint assessments. 
− For missed assessments for primary and secondary endpoints, please discuss these 
situations with the Sponsor for approval. In certain situations, with prior approval, other 
options, or delayed visits, can be considered. 
Monitoring and Audits 
• Certain Sponsor oversight responsibilities, such as monitoring and quality assurance activities need 
to be re-assessed and temporarily, alternative proportionate mechanisms of oversight may be 
required. On-site audits will be avoided or postponed, and if permitted under local regulations, 
physical distancing restrictions should apply. 
• Cancelling or postponing of on-site monitoring visits and extending of the period between 
monitoring visits will be allowed. 
• To the extent on-site monitoring remains feasible, it should consider national, local and/or 
organizational social distancing restrictions. 
• Centralized monitoring can be considered for data acquired by electronic data capture systems (e.g., 
eCRFs, central laboratory or ECG / imaging data, etc.) that are in place or could be put in place 
provides additional monitoring capabilities that can supplement and temporarily replace on-site 
monitoring through a remote evaluation of ongoing and/or cumulative data collected from study 
sites, in a timely manner. 
• Off-site monitoring can be conducted and will include phone calls, video visits, e-mails, or other 
online tools to discuss the study with the Investigator and site staff. Remote monitoring should be 
focused on review of critical study site documentation and source data. These activities could be 
used to get information on the clinical study progress, to exchange information on the resolution of 
problems, review of procedures, study subject status as well as to facilitate remote site selection and 
Investigator training for critical study procedures. 

 
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COVID-19 Vaccination 
• Various vaccines for COVID-19 have been approved worldwide. 
• Cancer patients, as part of the standard of care at their institution/country, receive COVID-19 
vaccine(s) in addition to anti-cancer therapy, including cytotoxic chemotherapy. This is supported by 
various published guidelines such as ASCO (https://www.asco.org/asco-coronavirus-
resources/covid-19-patient-care-information/covid-19-vaccine-patients-cancer) and ESMO 
(https://www.esmo.org/covid-19-and-cancer/covid-19-vaccination). 
• The Sponsor does not have specific data regarding any possible interaction between the COVID-19 
vaccines and SUPLEXA and has no evidence or rationale to suggest SUPLEXA alters the vaccine’s 
efficacy or increases the vaccine’s toxicity. However, given the uncertainty of the combination of 
this FIH product and COVID-19 vaccinations, COVID-19 vaccinations are not allowed within 30 
days prior to enrolment through 30 days after last infusion SUPLEXA infusion. 
Risk Mitigation 
• The Sponsor will continually assess whether the limitations imposed by the COVID-19 public health 
emergency on protocol implementation pose new safety risks to study subjects, and whether it is 
feasible to mitigate these risks by amending study processes and/or procedures. 
 
 

 
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10.10 
APPENDIX 10: GLOSSARY 
Abbreviation Term 
Description 
AE 
adverse event 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
BICR 
blinded independent central review  
BOCR 
best overall confirmed response  
CAR-T 
chimeric antigen receptor T cells  
CBC 
complete blood count 
CBR 
clinical benefit rate  
cGMP 
current Good Manufacturing Practice  
CPI 
checkpoint inhibitor 
CR 
complete response  
CrCl 
creatinine clearance 
CRS 
cytokine release syndrome 
CSF 
colony stimulating factors  
CT 
computed tomography  
CTCAE 
common terminology criteria for adverse events  
CTL 
cytotoxic CD8-positive T lymphocytes  
CTLA-4 
cytotoxic T-lymphocyte-associated protein 4  
DLT 
dose limiting toxicities  
DOR 
duration of response  
ECG 
electrocardiogram  
ECOG 
Eastern Cooperative Oncology Group  
eCRF 
electronic case report forms 
ENLiST 
ENgineered Leukocyte STimulator  
EOS 
end of study  
ET 
early termination 
FIH 
first in human 
FSH 
follicle stimulating hormone  
GCP 
Good Clinical Practice  
GFR 
glomerular filtration rate  

 
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Abbreviation Term 
Description 
HBsAg 
hepatitis B virus surface antigen  
hCG 
human chorionic gonadotropin  
HCV 
hepatitis C virus  
HIV 
human immunodeficiency virus  
HREC 
Australian Human Research Ethics Committee  
HRT 
hormonal replacement therapy  
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
DSMB 
Independent Data Monitoring Committee 
IFN 
interferon  
IHC 
immunohistochemistry  
IL 
interleukin  
INR 
international normalized ratio 
iRECIST 
Immune related RECIST 
IV 
intravenous 
LDH 
lactate dehydrogenase  
LLN 
lower limit of normal  
mAbs 
monoclonal antibody 
MDA 
Modified MD Anderson  
MedDRA 
medical dictionary for regulatory activities  
MHC 
major histocompatibility complex  
MRI 
magnetic resonance imaging  
MTD 
maximum tolerated cumulative dose  
NAE 
not all evaluated  
NCI 
National Cancer Institute  
NCNP 
RECIST assessment of non-CR/non-PD 
NCS 
not clinically significant  
NE 
not evaluable 
NHMRC 
National Health and Medical Research Council  
NIH 
National Institute of Health  
NK 
natural killer  
NKT 
natural killer T cells 

 
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Abbreviation Term 
Description 
NLR 
neutrophil/lymphocyte ratio  
ORR 
objective response rate  
OS 
overall survival  
PBMC 
peripheral blood mononuclear cells  
PD 
progressive disease 
PD-1 
programmed death-1  
PDX 
patient derived xenografts 
PFS 
progression-free survival  
PICF 
participant information sheet and informed consent form  
PO 
per os (by mouth) 
PR 
partial response  
PT 
prothrombin time  
QW 
once per week 
RECIST 
response evaluation criteria in solid tumours 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan  
SoA 
schedule of activities  
TCR 
T cell receptor  
TGA 
Australian Therapeutic Goods Administration 
TIL 
tumour infiltrating lymphocytes 
TLS 
tumour lysis syndrome  
TNF 
tumour necrosis factor 
TTP 
time to progression  
TTR 
time to response  
ULN 
upper limit of normal  
WOCBP 
women of childbearing potential 

 
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10.11 
APPENDIX 11: PROTOCOL AMENDMENT HISTORY 
The Protocol Amendment Summary of Changes Table for the current amendment is located directly 
before the Table of Contents (TOC). Prior amendments are provided in this section in chronological 
order. 
Amendment 1.0; 09 November 2021 
Overall Rationale for the Amendment: 
Summary of Changes (in order of appearance) 
Section Number and 
Name 
Description of Change 
Rationale for Change 
1.1 Synopsis (Overall Design) 
4.1.2 Treatment Period 
• Clarify staggering procedure 
• Clarify determination for treatment extension 
• To align with Study Schema and 
for clarity 
• Per request of HREC 
1.3 Schedule of Activities 
6.8.1 Prophylaxis 
• Clarify reason and timing of treatment 
prophylaxis 
• Per request of HREC 
2.3.1 Risk Assessment 
6.6 Toxicity Management 
10.6 CSR Toxicity Treatment 
Guidelines 
10.7 TLS Toxicity 
Management 
• Cross reference to CRS and TLS toxicity 
treatment guidelines which were added 
(Appendices 6 and 7) 
• For TLS, clarify summary of risk 
• Per request of HREC 
5.2 Exclusion Criteria 
• Add exclusion of subject at high risk for 
developing TLS 
• As a safety precaution 
5.2 Exclusion Criteria 
10.2 Appendix 2 Clinical 
Safety Laboratories 
• Delete exclusion criteria relating to coagulation 
• Delete coagulation parameters form laboratory 
tests 
• As biopsies will not be collected 
as part of this study no need to 
measure coagulation 
7.1 Study Stopping Rules 
• Add a study stopping criteria associated with 
DLTs 
• Clarify language around study stopping criteria 
• Per request of HREC 
8.4 Pharmacodynamics and 
Correlative Biomarkers 
• Moved text on disease biomarkers under this 
section and delete immunogenicity which is not 
assessed 
• For consistency and clarity 
General 
• Minor administrative changes and clarifications 
made throughout the protocol (e.g., blood 
volumes collected) 
• Correct typographical errors, hyperlinks/cross-
references, style, and formatting (not tracked). 
• Align across protocol sections. 
• Update glossary (not tracked). 
• Update header 
• For consistency and clarity 
• Alignment across documents 
Amendment 1.1; 30 November 2021 
Overall Rationale for the Amendment: 

 
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Summary of Changes (in order of appearance) 
Section Number and 
Name 
Description of Change 
Rationale for Change 
.1 Synopsis (Overall Design) 
1.3 Schedule of Activities 
4.1.2 Treatment Period 
6.1 Study intervention 
administered 
• Update procedures for subject safety monitoring 
post each infusion (3 hours at clinic post infusion 
and 24 hours each infusion) 
• Clarify that subjects who qualify for 3 additional 
weekly SUPLEXA infusions (Optional 
Treatment Extension period), will undergo 
similar evaluations as during the Treatment 
period 
• Update the SoA to incorporate above changes 
• For clarity 
• Per request of HREC 
General 
• Correct typographical errors, hyperlinks/cross-
references, style, and formatting (not tracked). 
• Align across protocol sections. 
• Update protocol section numbering, including 
adding Appendix 10 (protocol amendment 
history) 
• Update footer with version and date 
• For consistency and clarity 
• Alignment across protocol 
 
Amendment 1.2; 25December 2021 
Overall Rationale for the Amendment: 
Summary of Changes (in order of appearance) 
Section Number and 
Name 
Description of Change 
Rationale for Change 
1 Synopsis (Overall Design) 
1.3 Schedule of Activities 
4.1.2 Treatment Period 
6.1 Study intervention 
administered 
• Update procedures for subject safety monitoring 
post infusion for the first 3 subjects in each 
cohort and subsequent subjects 
• Update the SoA to incorporate above changes 
• Per request of HREC 
1.3 Schedule of Activities 
3. Objectives and Endpoints 
(exploratory) 
8.4 Pharmacodynamics and 
correlative biomarkers 
• Delete assessment of disease biomarkers (CEA 
and PSA) 
• Additional samples are not 
required as analysis will be done 
in the exploratory assessments 
General 
• Correct typographical errors, hyperlinks/cross-
references, style, and formatting (not tracked) 
• Align across protocol sections 
• Update protocol section numbering 
• Update footer with version and date 
• For consistency and clarity 
• Alignment across protocol 
 

 
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Amendment 2; 18 May 2022 
Overall Rationale for the Amendment: 
Summary of Changes (in order of appearance) 
Section Number and 
Name 
Description of Change 
Rationale for Change 
1.1 Synopsis 
1.2 Study Schema 
1.3 Schedule of Activities 
4.1 Overall Study Design 
• Extend screening to 35 days 
• For logistic reasons 
(Administrative Amendment #01) 
1.1 Synopsis 
1.3 Schedule of Activities 
4.1 Overall Study Design 
6.1 Study Intervention 
Administered 
• Specify assessments during the observation 
period post SUPLEXA administration 
• For clarity and to align with File 
Note dated 17 January 2022  
1.1 Synopsis 
4.1 Overall Study Design 
• Update enrolment process beyond the first 3 
subjects in each cohort 
• For manufacturing and logistical 
reasons 
1.3 Schedule of Activities 
6.8.1 Prophylaxis 
• Clarify that prophylactic measures listed in the 
protocol are recommended; site can follow 
standard of care. 
• To allow flexibility without 
compromising patient safety, 
premedication’s according to 
institutional practices will be 
permitted 
(Administrative Amendment #04) 
6.1 Study Intervention 
Administered 
• Update administration instruction 
• For alignment with the SUPLEXA 
therapeutic manual. Dilution range 
of SUPLEXA was widen from 
200-300mL to facilitate dilution at 
the clinical site as PlasmaLyte is 
not available in Australia in 
250mL bags units. The range has 
been validated through preclinical 
experiments and makes no 
difference to SUPLEXA cell 
viability. 
(Administrative Amendment #03) 
8.2.2 
• Update method(s) for collected temperature 
• Based on clinical site standard 
practice 
(Administrative Amendment #02) 
10.6 Appendix 6: CRS 
Toxicity Treatment Guidelines 
• Clarify CRS toxicity treatment guidelines 
• For clarity 
(File Note dated 11 February 
2022) 
General 
• Correct typographical errors, hyperlinks/cross-
references, style, and formatting (not tracked) 
• Align across protocol sections 
• Update protocol section numbering 
• Update footer with version and date 
• For consistency and clarity 
• Alignment across protocol 

 
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REFERENCES 
Ahrends, T. and Borst, J. (2018). "The opposing roles of CD4(+) T cells in anti-tumour immunity." 
Immunology. 
 
Alakel, N., Middeke, J. M., Schetelig, J. and Bornhauser, M. (2017). "Prevention and treatment of tumor 
lysis syndrome, and the efficacy and role of rasburicase." Onco Targets Ther 10: 597-605. 
 
Anguille, S., Smits, E. L., Lion, E., van Tendeloo, V. F. and Berneman, Z. N. (2014). "Clinical use of 
dendritic cells for cancer therapy." Lancet Oncol 15(7): e257-267. 
 
Australian Government (2020). COVID-19: Guidance on clinical trials for institutions, HRECs, 
researchers and sponsors. Department of Health and National Health and Medical Research Council. 
from https://www1.health.gov.au/internet/main/publishing.nsf/Content/Clinical-Trials. 
 
Cairo, M. S., Coiffier, B., Reiter, A., Younes, A. and Panel, T. L. S. E. (2010). "Recommendations for 
the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with 
malignant diseases: an expert TLS panel consensus." Br J Haematol 149(4): 578-586. 
 
Carding, S. R. and Egan, P. J. (2002). "Gammadelta T cells: functional plasticity and heterogeneity." 
Nat Rev Immunol 2(5): 336-345. 
 
Chawla, S. P., Kim, K. M., Chua, V. S., Jafari, O. and Song, P. Y. (2020). "Phase I study of SNK01 
(autologous non-genetically modified natural killer cells with enhanced cytotoxicity) in refractory 
metastatic solid tumors." Journal of Clinical Oncology 38(15_suppl): e15024-e15024. 
 
Costelloe, C. M., Chuang, H. H., Madewell, J. E. and Ueno, N. T. (2010). "Cancer Response Criteria 
and Bone Metastases: RECIST 1.1, MDA and PERCIST." J Cancer 1: 80-92. 
 
Crooks, V., Waller, S., Smith, T. and Hahn, T. J. (1991). "The use of the Karnofsky Performance Scale 
in determining outcomes and risk in geriatric outpatients." Journal of gerontology 46(4): M139-144. 
 
De Rosa, S. C., Andrus, J. P., Perfetto, S. P., Mantovani, J. J., Herzenberg, L. A., Herzenberg, L. A., et 
al. (2004). "Ontogeny of gamma delta T cells in humans." J Immunol 172(3): 1637-1645. 
 
Eisenhauer, E. A., Therasse, P., Bogaerts, J., Schwartz, L. H., Sargent, D., Ford, R., et al. (2009). "New 
response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1)." Eur J Cancer 
45(2): 228-247. 
 

 
Protocol Number: SUPLEXA-101 
 
Study intervention: SUPLEXA Therapeutic cells 
 
 
Confidential 
Page 104 of 106 
Version 4.0 Amendment 3,  
 
 
30 Sep 2022 
EMA. (2018). "Yescarta Assessment Report." from 
https://www.ema.europa.eu/en/medicines/human/EPAR/yescarta 
https://www.ema.europa.eu/en/documents/assessment-report/yescarta-epar-public-assessment-
report_en.pdf. 
 
EMA (April 2020). Guidance on the management of clinical trials during the COVID-19 (Coronavirus) 
pandemic, version 3, released 28 April 2020. Agency, E. M., from 
https://ec.europa.eu/health/sites/health/files/files/eudralex/vol-10/guidanceclinicaltrials_covid19_en.pdf. 
 
Fardis, M., DiTrapani, K., Garf Finckenstein, F. and Chartier, C. (2020). "Current and future directions 
for tumor infiltrating lymphocyte therapy for the treatment of solid tumors." Cell Gene Ther Insights 
6(6): 855-863. 
 
FDA (March 2020). FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-
19 Public Health Emergency – Guidance for Industry, Investigators and Institutional Review Boards. 
Updated January 27, 2021. U.S. Department of Health and Human Services Food and Drug 
Administration Center for Drug Evaluation and Research (CDER). from 
https://www.fda.gov/media/136238/download. 
 
Health Canada (03 April 2020). Management of clinical trials during the COVID-19 pandemic: Notice 
to clinical trial sponsors. from https://www.canada.ca/en/health-canada/services/drugs-health-
products/drug-products/announcements/management-clinical-trials-during-covid-19-pandemic.html. 
 
Hu, W., Wang, G., Huang, D., Sui, M. and Xu, Y. (2019). "Cancer Immunotherapy Based on Natural 
Killer Cells: Current Progress and New Opportunities." Front Immunol 10: 1205. 
 
Kruger, S., Ilmer, M., Kobold, S., Cadilha, B. L., Endres, S., Ormanns, S., et al. (2019). "Advances in 
cancer immunotherapy 2019 - latest trends." J Exp Clin Cancer Res 38(1): 268. 
 
Kyle B. Lupo, S. M. (2019). "Natural Killer Cells as Allogeneic Effectors in Adoptive Cancer 
Immunotherapy." Cancers (Basel). 11(6): 769. 
 
Lai, Y.-P., Jeng, C.-J. and Chen, S.-C. (2011). "The Roles of CD4+T Cells in Tumor Immunity." ISRN 
Immunology 2011: 497397. 
 
Larkin, J., Sarnaik, A., Chesney, J. A., Khushalani, N. I., Kirkwood, J. M., Weber, J. S., et al. (2021). 
"Lifileucel (LN-144), a cryopreserved autologous tumor infiltrating lymphocyte (TIL) therapy in 
patients with advanced melanoma: Evaluation of impact of prior anti-PD-1 therapy." J Clin Oncol 
39(15_suppl): 9505-9505. 

 
Protocol Number: SUPLEXA-101 
 
Study intervention: SUPLEXA Therapeutic cells 
 
 
Confidential 
Page 105 of 106 
Version 4.0 Amendment 3,  
 
 
30 Sep 2022 
 
Lee, D. W., Santomasso, B. D., Locke, F. L., Ghobadi, A., Turtle, C. J., Brudno, J. N., et al. (2019). 
"ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with 
Immune Effector Cells." Biol Blood Marrow Transplant 25(4): 625-638. 
 
Liu, D. (2019). "CAR-T "the living drugs", immune checkpoint inhibitors, and precision medicine: a 
new era of cancer therapy." J Hematol Oncol 12(1): 113. 
 
Liu, E., Marin, D., Banerjee, P., Macapinlac, H. A., Thompson, P., Basar, R., et al. (2020). "Use of 
CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors." N Engl J Med 382(6): 545-
553. 
 
Locke, F. L., Ghobadi, A., Jacobson, C. A., Miklos, D. B., Lekakis, L. J., Oluwole, O. O., et al. (2019). 
"Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-
1): a single-arm, multicentre, phase 1-2 trial." Lancet Oncol 20(1): 31-42. 
 
MHRA (22 April 2020). Guidance: Managing clinical trials during Coronavirus (COVID-19). from 
https://www.gov.uk/guidance/managing-clinical-trials-during-coronavirus-covid-19. 
 
Oh, S., Lee, J. H., Kwack, K. and Choi, S. W. (2019). "Natural Killer Cell Therapy: A New Treatment 
Paradigm for Solid Tumors." Cancers (Basel) 11(10). 
 
Ohtani, T., Yamada, Y., Furuhashi, A., Ohmura, Y., Nakamura, S., Kato, H., Kazaoka, Y. (2014). 
"Activated cytotoxic T-lymphocyte immunotherapy is effective for advanced oral and maxillofacial 
cancers. International Journal of Oncology, 45, 2051-2057. https://doi.org/10.3892/ijo.2014.2599." 
 
Ostroumov, D., Fekete-Drimusz, N., Saborowski, M., Kuhnel, F. and Woller, N. (2018). "CD4 and CD8 
T lymphocyte interplay in controlling tumor growth." Cell Mol Life Sci 75(4): 689-713. 
 
Pauza, C. D., Liou, M. L., Lahusen, T., Xiao, L., Lapidus, R. G., Cairo, C., et al. (2018). "Gamma Delta 
T Cell Therapy for Cancer: It Is Good to be Local." Front Immunol 9: 1305. 
 
Ribeiro, S. T., Ribot, J. C. and Silva-Santos, B. (2015). "Five Layers of Receptor Signaling in 
gammadelta T-Cell Differentiation and Activation." Front Immunol 6: 15. 
 
Shivani, S. and Stanley, R. R. (2018). "CAR T Cell Therapy: Challenges to Bench-to-Bedside Efficacy." 
J Immunol. 200 (2): 459–468. 
 

 
Protocol Number: SUPLEXA-101 
 
Study intervention: SUPLEXA Therapeutic cells 
 
 
Confidential 
Page 106 of 106 
Version 4.0 Amendment 3,  
 
 
30 Sep 2022 
Simoes, A. E., Di Lorenzo, B. and Silva-Santos, B. (2018). "Molecular Determinants of Target Cell 
Recognition by Human gammadelta T Cells." Front Immunol 9: 929. 
 
Vivier, E., Tomasello, E., Baratin, M., Walzer, T. and Ugolini, S. (2008). "Functions of natural killer 
cells." Nat Immunol 9(5): 503-510.