Clinical trial NCT02795988
Conditions: Gastrointestinal Neoplasms Adenocarcinoma
Keywords: Secondary
Sponsor: Imugene Limited
Start date: 2017-08-30; Completion date: 2024-03-20
Enrollment: 64 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The Phase 1b study is an open-label, multicenter dose escalation study designed to assess the safety, tolerability, immunogenicity and recommended phase 2 dose (RP2D) of IMU-131. The RP2D will be evaluated in the dose expansion Phase 2 study. The Phase 2 study is a randomized, open label comparison of IMU-131 plus standard of care chemotherapy versus standard of care chemotherapy alone.

Detailed description:

Arms: arm 1: 10, 30, 50μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine arm 2: 50 μg IMU-131 plus Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and Capecitabine. arm 3: Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and Capecitabine.
Interventions: intervention 1: IMU-131 intervention 2: Cisplatin and either Fluorouracil (5-FU) or Capecitabine or Oxaliplatin and capecitabine.
Intervention descriptions: intervention 1: IMU-131 vaccine is a P467-CRM197 peptide antigen in PBS buffer and Montanide ISA 51 Sterile adjuvant intervention 2: Chemotherapy will consist of: cisplatin by intravenous administration at 80 mg/m2 on the first day of each cycle and either 5-FU, 4000 mg/m2 CIV (administered as 1000 mg/m2/day as continuous infusion for 96 hours on days 1 to 4 of each cycle) or capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle), or (in Phase 2 only) oxaliplatin, by intravenous administration at 130 mg/m2 on Day 1 of each cycle and capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle).

Protocol documents:
Prot_000.pdf: 
Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED
Page 1 of 121
CONFIDENTIAL
HERIZON: A PHASE 1B/2 OPEN-LABEL STUDY OF IMU-131 HER2/NEU 
PEPTIDE VACCINE PLUS STANDARD OF CARE CHEMOTHERAPY WITH
RANDOMIZATION IN PHASE 2 IN PATIENTS WITH HER2/NEU
OVEREXPRESSING METASTATIC OR ADVANCED ADENOCARCINOMA OF 
THE STOMACH OR GASTROESOPHAGEAL JUNCTION
Compound:
IMU-131
Compound Name:
HER-Vaxx
Protocol Number:
IMU.ACS.001
Sponsor:
Imugene Limited
Suite 12.01, Level 12
4-6 Bligh Street
SYDNEY NSW 2000
Australia
Amendment:
5
Amendment Date:
27 September 2023
Approver’s Name and Title:
Signature: 
Date:
The name, title, address and telephone number(s) of the Sponsor's medical experts for the 
trial are documented in the study contact list located in the study coordinator’s manual. 
CONFIDENTIALITY STATEMENT:
This document and its contents are the property of and confidential to Imugene Limited and is being 
provided to you in confidence for review by you, your staff, and applicable ethics committee / 
institutional review board, and regulatory authorities. This document and its contents must not be copied 
or disclosed to others without Imugene Limited’s advance written approval.
NCT #: NCT02795988


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 2 of 121 
CONFIDENTIAL 
PROTOCOL ACCEPTANCE FORM 
HERIZON: A PHASE 1B/2 OPEN-LABEL STUDY OF IMU-131 HER2/NEU 
PEPTIDE VACCINE PLUS STANDARD OF CARE CHEMOTHERAPY WITH 
RANDOMIZATION IN PHASE 2 IN PATIENTS WITH HER2/NEU 
OVEREXPRESSING METASTATIC OR ADVANCED ADENOCARCINOMA OF 
THE STOMACH OR GASTROESOPHAGEAL JUNCTION 
Compound: 
IMU-131 
Compound Name: 
HER-Vaxx 
Protocol Number: 
IMU.ACS.001 
Sponsor: 
Imugene Limited  
Suite 12.01, Level 12 
4-6 Bligh Street
SYDNEY NSW 2000
Australia
Amendment: 
5 
Amendment Date: 
27 September 2023 
I agree to conduct the study in accordance with the current protocol. 
Principal Investigator’s Name (print) 
Principal Investigator’s Signature 
Date 
Please keep the signed original form in your investigator site file and return a copy to 
your local study monitor.  


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 3 of 121 
CONFIDENTIAL 
DOCUMENT HISTORY 
Document 
Version Date 
Summary of Changes 
Original protocol 
6 April 2016 
N/A 
Thailand 
specific 
protocol 
addenda #1 
2 February 2017 
Additional Exclusion Criteria to 
exclude patients with diphtheria 
toxoid hypersensitivity. 
See Appendix 4. 
Taiwan 
specific 
protocol 
addenda #1 
13 March 2017 
To confirm the sequential enrolment 
of Taiwanese patients - at least 
14 days apart in the first dose 
cohort. 
To increase the observation time for 
Taiwan patients dosed in the study to 
6 hours post first injection. 
See Appendix 5. 
Global Amendment #1 
2 August, 2017 
Update Sponsor address 
Modify Inc#6 to allow inclusion of 
patients with IHC HER2++ 
expression.  
Modify Inc#8 to allow inclusion of 
patients without measurable disease. 
Include justification for 2 injections 
before start of chemotherapy. 
Separate heading for DLT 
definition. 
Update post-study SAE reporting 
period to coincide with 28-day post-
study AE reporting period 
Include re-screening process 
 
for vaccine and adjuvant. 
Remove Appendix 2 details and 
indicate moved to study file.  
Include Thailand specific addenda 
2 Feb 17  
Include Taiwan specific addenda 
13 Mar 17 
Various typographical and 
grammatical corrections. 
Update references. 
Global Amendment #2 
23 November 2018 
Update introduction with Phase 1b 
results 
Update with detail for Phase 2 part 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 4 of 121 
CONFIDENTIAL 
Document 
Version Date 
Summary of Changes 
of the protocol 
Re-arrange order of sections 
Various typographical and 
grammatical corrections 
Update references 
Global Amendment #3 
17 February 2021 
Modify title, change principal 
physician 
Modify number patients to be 
enrolled and number of events 
required to meet endpoints 
Modify exploratory endpoint 
analysis 
Add optional post-progression 
tumor sample 
Update protocol to align with notes 
to file including correction of tumor 
‘grade’ to ‘stage’, addition of 
telemedicine process, clarification of 
AE/SAE reporting for ineligible and 
re-screened patients.  
Global Amendment #4 
12 August 2021 
Addition of Phase 2 Extension study 
to examine safety and efficacy of 
higher doses of IMU-131. 
Update to Phase 2 statistical section 
to align protocol and SAP. 
Addition of references, and 
grammatical corrections. 
Global Amendment #5 
TBA 
Clarification of end of study 
Modified contraception and 
pregnancy timelines.   
Removed reference to arms from 
Phase 2 Extension objectives and 
endpoints 
Addition of future use of samples 
Removed Moldova as participating 
country in Phase 2 Extension 
Updated Sponsor address 
Updated DLT criteria to be 
consistent throughout 
Other formatting and administrative 
changes 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 5 of 121 
CONFIDENTIAL 
TABLE OF CONTENTS 
PROTOCOL ACCEPTANCE FORM ................................................................................. 2 
DOCUMENT HISTORY ..................................................................................................... 3 
LIST OF ABBREVIATIONS ............................................................................................ 11 
CLINICAL PROTOCOL SYNOPSIS ............................................................................... 15 
SCHEDULE OF ACTIVITIES .......................................................................................... 39 
1.
INTRODUCTION ................................................................................................. 47 
1.1. 
Indication ........................................................................................................ 47 
1.2. 
Background and Rationale .............................................................................. 47 
1.3. 
IMU-131 (HER2/neu Peptide Vaccine) ......................................................... 48 
1.4. 
Risk/Benefit analysis for IMU-131 (HER2/neu Peptide Vaccine)................ 52 
2.
STUDY OBJECTIVES AND ENDPOINTS ........................................................ 53 
2.1. 
Objectives ....................................................................................................... 53 
2.2. 
Endpoints ........................................................................................................ 55 
3.
STUDY DESIGN................................................................................................... 58 
4.
PATIENT STUDY ENROLMENT AND DISCONTINUATION ....................... 62 
4.1. 
Inclusion Criteria ............................................................................................ 62 
4.2. 
Exclusion Criteria ........................................................................................... 63 
4.3. 
Contraception Guidelines ............................................................................... 64 
5.
STUDY TREATMENTS....................................................................................... 64 
5.1. 
Allocation to Treatment .................................................................................. 64 
5.2. 
Vaccine Supplies ............................................................................................ 65 
5.2.1. Formulation and Packaging .......................................................................65 
5.2.2. Preparation and Dispensing .......................................................................65 
5.2.3. Administration ...........................................................................................67 
5.2.4. Compliance ................................................................................................68 
5.3. 
Drug Storage and Drug Accountability .......................................................... 69 
5.4. 
Concomitant Medication(s) ............................................................................ 69 
5.4.1. Permitted medications ...............................................................................69 
5.4.2. Prohibited medications ...............................................................................69 
6.
STUDY PROCEDURES ....................................................................................... 69 
6.1. 
Screening (Phase 1b and Phase 2/Phase 2 Extension) ................................... 70 
6.1.1. Re-Screening ..............................................................................................71 
6.2. 
Phase 1b Study Period .................................................................................... 71 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 6 of 121 
CONFIDENTIAL 
6.2.1. Phase 1b Vaccination procedure (Day 0, 14 and 35) ................................71 
6.2.2. Phase 1b Dose Period 1 (Day 0 and Day 2) ..............................................72 
6.2.3. Phase 1b Dose Period 2 (Day 14 and Day 16) ..........................................72 
6.2.4. Phase 1b Dose Period 3 (Day 35 and Day 37) ..........................................73 
6.2.5. Phase 1b End of Treatment Visit (Day 56) ...............................................73 
6.2.6. Phase 1b chemotherapy only visit (Day 77) .............................................74 
6.2.7. Phase 1b Follow-up Post-Withdrawal Visit (30 – 40 days after last 
vaccination) ................................................................................................74 
6.2.8. Phase 1b Unscheduled Visit ......................................................................74 
6.3. 
Phase 1b Long Term Maintenance of Phase 1b patients (Day 98 onwards) . 75 
6.4. 
Phase 2 and Phase 2 Extension Study Period ................................................ 75 
6.4.1. Phase 2 and Phase 2 Extension Vaccination procedure ............................75 
6.4.2. Phase 2 and Phase 2 Extension Baseline/Day 0 .......................................76 
6.4.3. Phase 2 and Phase 2 Extension Week2/Day 14 (only for patients in IMU-
131 plus chemotherapy cohorts) ................................................................76 
6.4.4. Phase 2 and Phase 2 Extension Week 3/Day 21 .......................................77 
6.4.5. Phase 2 and Phase 2 Extension Week 5/Day 35 (only for patients in IMU-
131 plus chemotherapy cohorts) ................................................................77 
6.4.6. Phase 2 and Phase 2 Extension Week 6/Day 42 .......................................77 
6.4.7. Phase 2 and Phase 2 Extension Week 9/Day 63 .......................................78 
6.4.8. Phase 2 and Phase 2 Extension Week 11/Day 77 (only for patients in IMU-
131 plus chemotherapy cohorts) ................................................................78 
6.4.9. Phase 2 and Phase 2 Extension Week 12/Day 84 (Repeat every 12 
weeks/84 days) ...........................................................................................78 
6.4.10. Phase 2 and Phase 2 Extension Week 15/Day 105 ...................................79 
6.4.11. Phase 2 and Phase 2 Extension Week 18/Day 126 (Repeat every 12 
weeks/84 days) ...........................................................................................79 
6.4.12. Phase 2 and Phase 2 Extension Week 20/Day 140 (Repeat every 9 week/63 
days - only for patients in IMU-131 plus chemotherapy cohorts) .............79 
6.4.13. Phase 2 and Phase 2 Extension End of Treatment (EoT) Visit .................80 
6.4.14. Phase 2 Post-Treatment Follow-up Visit (Every 42 days after EoT visit) .80 
6.4.15. Phase 2 and Phase 2 Extension Unscheduled Visit ...................................80 
6.5. 
Patient Withdrawal ......................................................................................... 81 
6.5.1. Main discontinuation criteria .....................................................................81 
6.5.2. Contraindications to repeated vaccination ................................................81 
6.5.3. Additional Discontinuation Criteria ..........................................................81 
7.
PHASE 1B ASSESSMENTS ................................................................................ 82 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 7 of 121 
CONFIDENTIAL 
7.1. 
Phase 1b Physical Examination (Screening, Days 0, 14, 35, 56, 77, 98, LTM 
visits) ............................................................................................................... 82 
7.2. 
Phase 1b Height, Weight and Vital Signs (Screening, Days 0, 14, 35, 56, 77, 
98, LTM visits) ............................................................................................... 82 
7.3. 
Phase 1b Radiographic Assessment (Screening, Days 56, 98, LTM visits).. 82 
7.4. 
Phase 1b Cardiac Assessment (Screening, Day 56) ...................................... 83 
7.5. 
Phase 1b Laboratory Assessments.................................................................. 83 
7.5.1. Phase 1b Safety Laboratory Assessments (Screening, Days 0, 14, 35, 56, 
77, 98, LTM visits) .....................................................................................83 
7.5.2. Phase 1b Immunologic Assessments (Screening, Days 0, 14, 35, 56, 77, 
98, LTM visits) ...........................................................................................84 
7.5.3. Phase 1b HER2/neu overexpression (Screening) ......................................84 
7.5.4. Phase 1b ECOG performance grade (Screening) ......................................85 
7.6. 
Phase 1b Vaccination site evaluation (Days 2, 16, 37).................................. 85 
7.7. 
Phase 1b Pregnancy Test (Screening, Days 0, 14, 35, 98, LTM visits) ........ 85 
8.
PHASE 2 AND PHASE 2 EXTENSION ASSESSMENTS................................. 85 
8.1. 
Assessments via Telemedicine ....................................................................... 85 
8.2. 
Phase 2 and Phase 2 Extension Physical Examination (Screening, Baseline, 
Days 21, 42, 63, 84, 105, 126 then every 42 days and EoT visit) .................. 86 
8.3. 
Phase 2 and Phase 2 Extension Height, Weight, Vital Signs, Concomitant 
Medications, Concomitant Procedures and Adverse Events (at each study 
visit, excluding post-treatment follow-up visits) ............................................ 86 
8.4. 
Phase 2 and Phase 2 Extension Radiographic Assessment (Baseline, Days 
42, 84, 126 then every 42 days) ...................................................................... 86 
8.5. 
Phase 2 and Phase 2 Extension Cardiac Assessment (Screening, Day 84 then 
every 84 days and EoT visit) .......................................................................... 86 
8.6. 
Phase 2 and Phase 2 Extension Laboratory Assessments .............................. 86 
8.7. 
Phase 2/Phase 2 Extension HER2/neu overexpression (Screening) .............. 88 
8.8. 
Phase 2/Phase 2 Extension ECOG performance grade (Screening, Baseline, 
Days 84 then every 84 days and EoT visit) .................................................... 88 
8.9. 
Phase 2/Phase 2 Extension Pregnancy Test (at each study visit, excluding 
post- treatment follow-up visits) ..................................................................... 88 
8.10. Phase 2/Phase 2 Extension Intra-tumor analysis (Screening, Day 84 and post- 
progression) ..................................................................................................... 88 
8.11. Phase 2/Phase 2 Extension Unscheduled Visit .............................................. 88 
8.12. Phase 2 Post-treatment Follow Up (FU) Visit (Every 42 days after EoT visit)
 ........................................................................................................................ 89 
9.
ADVERSE EVENT REPORTING ....................................................................... 89 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 8 of 121 
CONFIDENTIAL 
9.1. 
Adverse Events ............................................................................................... 89 
9.2. 
Reporting Period ............................................................................................. 90 
9.3. 
Definition of an Adverse Event...................................................................... 90 
9.4. 
Abnormal Test Findings ................................................................................. 91 
9.5. 
Serious Adverse Events .................................................................................. 91 
9.5.1. Adverse Events of Special Interest ............................................................91 
9.6. 
Hospitalization ................................................................................................ 92 
9.7. 
Adverse Event Severity Assessment .............................................................. 93 
9.7.1. Local (injection site) Adverse Event Intensity: .........................................93 
9.7.2. Other Adverse Event Intensity Grading ....................................................94 
9.8. 
Causality Assessment ..................................................................................... 95 
9.9. 
Pregnancy ........................................................................................................ 95 
9.10. Withdrawal Due to Adverse Events (See Also Section 6.5: Patient 
Withdrawal) .................................................................................................... 96 
9.11. Eliciting Adverse Event Information .............................................................. 96 
9.12. Reporting Requirements ................................................................................. 96 
9.12.1. Serious Adverse Event Reporting Requirements ......................................96 
9.12.2. Non-Serious Adverse Event Reporting Requirements ..............................97 
9.12.3. Sponsor Reporting Requirements to Regulatory Authorities ...................97 
10.
DATA ANALYSIS/STATISTICAL METHODS ................................................ 97 
10.1. Phase 1b Cohort Review Committee (CRC).................................................. 97 
10.1.1. Phase 1b Definition of Dose-Limiting Toxicity (DLT) ............................97 
10.1.2. Phase 1b Dose Escalation ..........................................................................98 
10.2. Phase 1b Analysis ........................................................................................... 98 
10.2.1. Phase 1b Efficacy Analysis .......................................................................99 
10.2.2. Phase 1b Safety Analysis ...........................................................................99 
10.2.3. Phase 1b Interim Analysis .........................................................................99 
10.3. Phase 2 Independent Data Monitoring Committee (IDMC) ....................... 100 
10.4. Phase 2 Analysis ........................................................................................... 100 
10.4.1. Phase 2 Analysis Populations ..................................................................100 
10.4.2. Phase 2 Efficacy Analysis ........................................................................100 
10.4.3. Phase 2 Safety Analysis ...........................................................................101 
10.5. Phase 2 Dose Escalation Cohort Review Committee (CRC) ...................... 101 
10.5.1. Phase 2 Dose Escalation Definition of Dose-Limiting Toxicity (DLT) .102 
10.5.2. Phase 2 Dose Escalation ..........................................................................102 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 9 of 121 
CONFIDENTIAL 
10.6. Phase 2 Extension Analysis .......................................................................... 103 
10.6.1. Phase 2 Dose Escalation Safety Analysis ...............................................104 
10.6.2. Phase 2 Dose Escalation Interim Analysis ..............................................104 
10.6.3. Phase 2/Phase 2 Extension General Considerations ...............................104 
10.7. Sample Size Determination .......................................................................... 105 
10.7.1. Phase 1b Sample Size Determination ......................................................105 
10.7.2. Phase 2 Sample Size Determination ........................................................105 
10.7.3. Phase 2 Extension Sample Size Determination .......................................106 
11.
DATA HANDLING AND RECORD KEEPING .............................................. 106 
11.1. Case Report Forms/Electronic Data Record ................................................ 106 
11.2. Record Retention .......................................................................................... 106 
12.
ETHICS................................................................................................................ 107
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) .. 107 
12.2. Ethical Conduct of the Study ....................................................................... 107 
12.3. Patient Information and Consent .................................................................. 107 
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
 ...................................................................................................................... 108 
13.
STUDY CONDUCT CONSIDERATIONS ........................................................ 108 
13.1. Protocol and Investigator’s Brochure (IB) ................................................... 108 
13.2. Confidentiality .............................................................................................. 108 
13.3. Documentation and Material Supplies ......................................................... 109 
13.4. Monitoring .................................................................................................... 109 
13.5. Quality Assurance Audit .............................................................................. 109 
13.6. Compensation for Medicine-induced Injury ................................................ 109 
14.
DEFINITION OF END OF TRIAL .................................................................... 110 
15.
SPONSOR DISCONTINUATION CRITERIA ................................................. 110 
16.
PUBLICATION OF DATA AND PROTECTION OF TRADE SECRETS ..... 110 
17.
REFERENCES .................................................................................................... 112 
APPENDIX 1: FLOW DIAGRAM OF PHASE 1B ....................................................... 115 
APPENDIX 2: VACCINE – MONTANIDE EMULSION PREPARATION 
INSTRUCTIONS ................................................................................................. 116 
APPENDIX 3: ECOG PERFORMANCE GRADE SCALE.......................................... 117 
APPENDIX 4: THAILAND SPECIFIC PROTOCOL ADDENDA #1 ........................ 118 
APPENDIX 5: TAIWAN SPECIFIC PROTOCOL ADDENDA #1 ............................. 119 
APPENDIX 6: FLOW DIAGRAM OF PHASE 2 .......................................................... 121 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 10 of 121 
CONFIDENTIAL 
TABLES 
Table 1: 
Schedule of Activities Phase 1b .....................................................................39 
Table 2: 
Schedule of Activities Long Term Maintenance ............................................41 
Table 3: 
Schedule of Activities Phase 2 and Phase 2 Extension ..................................43 
Table 4: 
Grading of Local Adverse Event Intensity .....................................................94 
Table 5: 
Common Toxicity Criteria for Adverse Events version 4.03 (CTCAE 
v4.03) and version 5.0 (CTCAE v5.0) Grading ..............................................94 
FIGURES 
Figure 1: 
Timeline for Phase 1b .....................................................................................60 
Figure 2: 
Timeline for Phase 2 ......................................................................................61 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 11 of 121 
CONFIDENTIAL 
LIST OF ABBREVIATIONS 
°C 
degree Celsius 
µg 
microgram 
µL 
microliter 
5-FU
5-fluorouracil
ACS
Advanced cancer of the stomach
ADCC
Antibody-dependent cellular cytotoxicity
AE(s)
Adverse event(s)
ALT
alanine aminotransferase
ANC
absolute neutrophil count
AST
aspartate aminotransferase
B cell
B lymphocyte
BDISH
brightfield double in situ hybridization
BHCG
beta-human chorionic gonadotrophin
BSA
Body Surface Area
BUN
blood urea nitrogen
CBC
complete blood count
CDC
complement-dependent cytotoxicity
CEA
Carcinoembryonic antigen
CISH
chromogenic in situ hybridization
CIV
continuous intravenous infusion
CR
Complete Response
CRC
Cohort Review Committee
CRF
Case report form
CRO
Contract research organization-
CRP
C-reactive protein
CT
Computed tomography
CTCAE
National Cancer Institute’s Common Toxicity Criteria for Adverse Events
CTS
Change in Tumor Size
DCR
Disease Control Rate
DLT
Dose-limiting toxicity
DOR
Duration of Response
ECD
extracellular Domain
ECG
Electrocardiogram


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 12 of 121 
CONFIDENTIAL 
ECOG 
Eastern Cooperative Oncology Group 
EGF 
epithelial growth factor  
ER 
Emergency Room   
EVAL 
Evaluable Set   
FAS 
Full Analysis Set  
FDA 
US Food and Drug Administration 
FISH 
Fluorescent in situ hybridization 
GCP 
Good Clinical Practice 
GEJ 
Gastroesophageal junction 
GGT 
gamma glutamyl transpeptidase 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HER2/neu 
Human epidermal growth factor receptor 2 
HIV 
Human Immunodeficiency Virus 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonization 
IDMC 
Independent Data Monitoring Committee 
IgG 
Immunoglobulin G 
IHC 
Immunohistochemistry 
IM 
Intramuscular(ly) 
IMU 
Imugene Limited, Australia 
IMU-131 
Investigational product consisting of P467-CRM in Montanide adjuvant 
IRB/IEC 
Institutional review board/independent ethics committee 
ISA 
Industry Standard Architecture 
ITT 
Intent-to-Treat   
IUD 
intrauterine device 
IUS 
intrauterine system 
IV 
Intravenous(ly) 
IxRS 
Interactive Voice or Web Response System   
LDH 
lactate dehydrogenase 
LLN 
Lower limit of normal 
LTM 
Long-term Maintenance   
LVEF 
Left ventricular ejection fraction 
m 
mass 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 13 of 121 
CONFIDENTIAL 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
milligram 
mL 
milliliter 
mm 
millimeter 
MUGA 
Multiple gated acquisition (scan) 
N 
number 
NCCN 
US National Comprehensive Cancer Network® 
NCI 
National Cancer Institute 
NICE 
National Institute for Health and Care Guidance 
NSCLC 
Non-small cell lung cancer 
NYHA 
New York Heart Association 
ORR 
Objective Response Rate 
OS 
Overall survival 
PBMC 
peripheral blood mononuclear cell 
PBS 
phosphate-buffered saline 
PD 
Progressive Disease  
PEV6C 
First generation formulation of IMU-131 
PFS 
Progression Free Survival 
PI 
Principal Investigator   
PP 
Per-Protocol   
PR 
Partial Response  
RBC 
Red blood cell 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RNA 
ribonucleic acid 
RP2D 
recommended phase 2 dose 
S.A. 
société anonyme 
SAE(s) 
Serious adverse event(s) 
SAP 
Statistical analysis plan 
SD 
Stable Disease  
SOC 
standard of care 
T cell 
T lymphocyte  
TEAEs 
Treatment-emergent Adverse Events  
ToGA 
Trastuzumab for Gastric Cancer 
TTP 
Time to Progression 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 14 of 121 
CONFIDENTIAL 
ULN 
Upper limit of normal 
WBC 
White blood cell 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 15 of 121 
CONFIDENTIAL 
CLINICAL PROTOCOL SYNOPSIS 
Study Number 
and Title 
IMU.ACS.001 
HERIZON: A Phase 1b/2 Open-label Study of IMU-131 HER2/neu 
Peptide Vaccine Plus Standard of Care Chemotherapy with 
randomization in Phase 2 in Patients with HER2/neu Overexpressing 
Metastatic or Advanced Adenocarcinoma of the Stomach or 
Gastroesophageal Junction 
Sponsor 
Imugene Limited 
Indication 
HER2/neu overexpressing metastatic or advanced adenocarcinoma of the 
stomach or gastroesophageal junction, also known as Advanced Cancer 
of the Stomach (ACS). 
Number of 
patients 
Multicenter with a maximum of 18 patients enrolled in Phase 1b and 
approximately 36 patients enrolled in Phase 2. 
Phase 2 Extension will enroll up to 20 patients: 3-9 patients during dose 
escalation with either dose cohort expanded up to 10 patients. 
Clinical Phase 
The Phase 1b study is an open-label, multicenter dose escalation study 
designed to assess the safety, tolerability, immunogenicity and 
recommended phase 2 dose (RP2D) of IMU-131. The RP2D will be 
evaluated in the dose expansion Phase 2 study which will be submitted as 
an amendment to this Phase 1b/2 protocol during the conduct of the Phase 
1b study. 
Phase 2 is an open-label, randomized, multicenter study designed to 
assess the clinical activity, immunogenicity, safety and tolerability of 
IMU-131. The length of Phase 2 will be approximately 30 months: 22 
months’ recruitment and an estimated 8 months’ follow-up from 
completion of recruitment to realization of the required number of deaths. 
It is anticipated that an additional 3 months will be required to complete 
the analyses following realization of the last required death. 
Phase 2 Extension: dose escalation in Phase 2 is an open-label, 
multicenter, 
single 
arm 
study 
to 
assess 
safety, 
tolerability, 
immunogenicity, and preferred dose for further development of IMU-131. 
The duration of Phase 2 dose escalation study will be approximately 
24 months: 15 months for recruitment and approximately 12 months on 
study. 
Once the last enrolled patient completes the end of treatment visit, the 
Sponsor may close the study. 
Rationale 
Almost one million new cases of gastric cancer were estimated to have 
occurred worldwide in 2012, making it the fifth most common 
malignancy in the world and the third leading cause of cancer death in 
both sexes worldwide. HER2/neu is overexpressed in 15% to 25% of 
patients with gastric cancer and is associated with a worse prognosis, 


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more aggressive disease, and poorer survival. While the addition of a 
monoclonal antibody against HER2/neu (trastuzumab) to cisplatin and 
either 5-fluorouracil (FU) or capecitabine chemotherapy has shown 
significant benefit over chemotherapy alone, alternative treatments are 
needed because trastuzumab is not available everywhere, is costly, and is 
associated with potentially serious side effects. 
IMU-131 is a single peptide structure composed of 3 individual B-cell 
epitope peptide sequences selected from HER2/neu structure. Polyclonal 
antibodies against IMU-131 peptides bind three separate regions of the 
HER2 receptor and also to the dimerization loop of the HER2 receptor, 
preventing dimerization, which in turn inhibits intracellular signaling. 
This blockade of the HER2 signaling pathways is thought to be 
substantially greater than that with trastuzumab alone. Safety and 
immunogenicity of the 3 peptides have been shown in Phase 1 testing of 
an earlier formulation of IMU-131. The shelf stability of the Phase 1 
vaccine was not optimal and hence the formulation was adjusted for IMU- 
131. The three B-cell epitope peptides (P4, P6 and P7) were combined in
a specific order resulting in a single fusion peptide of 49 amino acids in
length (P467). This new formulation of IMU-131 has extended stability
and improved immunogenicity compared to the formulation used
previously. The new vaccine IMU-131 produces a stronger and more
rapid polyclonal antibody response and is efficient to manufacture
compared with previous formulations. Based on these three known
epitopes (P4, P6 and P7), we developed a single peptide antigen (P467),
which allows simplification of the manufacturing process. First, only one
batch of peptide needs to be produced and qualified. Second,
compatibility problems during the formulation process due to different
physico-chemical properties of different peptides are circumvented.
Third, equal dosing of the three epitopes in the formulation is inherently
guaranteed with a single peptide.
It is hypothesized that administration of IMU-131 in addition to 
chemotherapy will prolong survival and may delay tumor progression 
and/or reduce tumor burden in patients with HER2/neu overexpressing 
gastric or gastroesophageal junction (GEJ) adenocarcinoma. 
This phase1b/2 protocol is made up of 2 components. The first component 
is the Phase 1b study, which is wholly detailed in this protocol. The 
second component consists of the Phase 2 evaluation of clinical activity 
of IMU-131 which will be submitted as an amendment to this phase 1b/2 
protocol after initiation of the Phase 1b study. 
The Phase 1b study aims to determine the safety and tolerability of IMU-
131 and identify the Recommended Phase 2 Dose (RP2D) of IMU-131 
in combination with chemotherapy in HER2/neu overexpressing ACS to 
carry into the Phase 2 dose expansion study. The Phase 2 component will 
be submitted as an amendment and will be initiated following 
completion of Phase 1b. Phase 2 will be designed to further characterize 
the safety and to explore clinical activity of IMU-131 in combination with 


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chemotherapy in HER2/neu overexpressing ACS. 
Phase 2 Extension 
Further increasing the dose of IMU-131 is supported by safe 
administration based on existing clinical data with no IMU-131 related 
safety signals, dose limiting toxicities, or SUSARs reported during either 
the Phase 1b or Phase 2 study. The selection of the 
 dose for Phase 2 
was based on Her2/neu antibody development and response compared to 
the lower dose levels studied and not on any IMU-131 related toxicity. 
To explore further treatment options for different treatment lines of 
GC/GEJ cancer, in particular after progression on trastuzumab, a higher 
dose than currently used in Phase 2 is considered a potentially stronger 
treatment option. 
Safety data from the 36 patient Phase 2 study supports dose escalation 
-131 because no IMU-131 related safety signals, dose
limiting toxicities, or SUSARs have been reported. 
IMU-131, to further characterize the safety, clinical activity, and 
immunogenicity of IMU-131 with SOC chemotherapy as first-line 
treatment for HER2/neu overexpressing metastatic/advanced gastric or 
GEJ cancer. 
Objectives 
Objectives of Phase 1b study: 
To evaluate the safety and tolerability of IMU-131 administered 
intramuscularly (IM) and initiated 14 days (+/- 1 day) prior to 
cisplatin, intravenous (IV) and either 5-FU, IV or capecitabine, 
oral chemotherapy in patients with HER2/neu overexpressing 
ACS;
To identify the Recommended Phase 2 Dose of IMU-131, 
administered IM and initiated 14 days (+/- 1 day) prior to 
chemotherapy in patients with HER2/neu overexpressing ACS for 
evaluation in Phase 2.
Exploratory objectives of Phase 1b study: 
Humoral and tumoral immunogenicity data will be used to further 
explore the mechanism of action for anti-tumor effects of IMU- 
131;
Radiographic data will be used for an exploratory determination 
of Response Rate.
Phase 2 Primary Objective: 
To evaluate the clinical efficacy of IMU-131 plus chemotherapy 
compared to chemotherapy alone based on overall survival (OS). 
Phase 2 Secondary Objectives: 
To evaluate other efficacy measures of IMU-131 plus 
chemotherapy compared to chemotherapy alone including 


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progression-free survival (PFS), time to progression (TTP), 
disease control rate (DCR), objective response rate (ORR), 
duration of objective response (DOR) and change in tumor size 
(CTS) according to Response Evaluation Criteria In Solid Tumors 
version 1.1 (RECIST 1.1) for the progression evaluation of 
radiographic data. 
To evaluate the safety profile of IMU-131 plus chemotherapy 
compared to chemotherapy alone. 
Phase 2 Exploratory Objectives: 
To evaluate humoral and cellular immunogenicity data of IMU- 
131 plus chemotherapy compared to chemotherapy alone 
including 
P467-specific 
antibodies 
(IgG), 
Her-2-specific 
antibodies (IgG), vaccine-specific cytokine levels and regulatory 
and effector T and B cells. 
To evaluate the arm-specific associations between clinical 
outcome, intra-tumor T cells, regulatory and effector T and B 
cells, and serum and biochemical markers of tumor progression. 
To evaluate arm-specific associations between clinical outcome 
and HER2 and PD-L1 expression in tumor tissue. 
To evaluate inhibition of in-vitro tumor cell growth and intra- 
cellular signaling processes by Her-2-specific antibodies (IgG) 
Phase 2 Dose Escalation Primary Objective: 
IMU-131 in combination with chemotherapy. 
Phase 2 Dose Escalation Secondary Objectives: 
To evaluate efficacy of IMU-131 plus chemotherapy including 
OS, PFS, TTP, ORR, DOR, DCR, and CTS according to Response 
Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) for 
the progression evaluation of radiographic data. 
Phase 2 Dose Escalation Exploratory Objectives: 
To evaluate humoral and cellular immunogenicity data of IMU-
131 plus chemotherapy compared to chemotherapy alone 
including 
P467-specific 
antibodies 
(IgG), 
Her-2-specific 
antibodies (IgG), vaccine-specific cytokine levels and regulatory 
and effector T and B cells. 
To evaluate associations between clinical outcome, intra-tumor T 
cells, regulatory and effector T and B cells, and serum and 
biochemical markers of tumor progression. 
To evaluate associations between clinical outcome and HER2 and 
PD-L1 expression in tumor tissue. 
To evaluate inhibition of in-vitro tumor cell growth and intra- 


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cellular signaling processes by Her-2-specific antibodies (IgG). 
Endpoints 
Phase 1b study endpoints: 
The safety and tolerability of IMU-131 will be evaluated by 
adverse events (AEs) and laboratory measurements. AEs and 
laboratory abnormalities will be graded by Common Terminology 
Criteria for Adverse Events (CTCAE) v4.03;
The recommended phase 2 dose will be evaluated by 
safety/tolerability and immunogenicity data for IMU-131 (P467- 
specific antibodies (IgG) and Her-2- specific antibodies (IgG) 
titers).
Phase 1b study exploratory endpoints: 
Humoral and cellular immunogenicity data will include P467- 
specific antibodies (IgG) and Her-2- specific antibodies (IgG) in 
serum samples and vaccine-specific cytokine levels as well as 
analysis of regulatory and effector T and B cells taken across study 
visits. As prediction markers of tumor progression initial 
evaluation (prior first vaccination) of intra-tumor T cells and 
regulatory cells in tumor biopsies will be performed, when these 
tests are available at the hospital pathology laboratory.
Radiographic data will be analyzed descriptively to explore 
Response Rate and provide information for sample size 
calculation for the Phase 2 study.
Phase 2 Primary Efficacy Endpoint: 
 
OS measured from randomization to death due to any cause. 
Phase 2 Secondary Efficacy Endpoints:
PFS measured from randomization to date of earliest progressive 
disease (PD) based on blinded central review according to 
RECIST 1.1 criteria, or to date of death from any cause.
TTP measured from randomization to date of earliest PD based on 
blinded central review according to RECIST 1.1 criteria. 
DCR measured from randomization as the proportion of patients 
achieving a confirmed best overall response of complete response 
(CR), partial response (PR) or stable disease (SD) based on 
blinded central review according to RECIST 1.1 criteria. 
ORR measured from randomization as the proportion of patients 
achieving a confirmed best overall response of CR or PR based on 
blinded central review according to RECIST 1.1 criteria. 
DOR measured from when earliest CR or PR is observed to PD or 
death due to any cause based on blinded central review according 
to RECIST 1.1 criteria. 
Percentage CTS measured from randomization as the sum of 


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diameters based on blinded central review according to RECIST 
1.1 criteria. 
Phase 2 Exploratory Endpoints: 
Values and changes from randomization in humoral and cellular 
immunogenicity data including P467-specific antibodies (IgG), 
Her-2-specific antibodies (IgG), vaccine-specific cytokine levels 
and regulatory and effector T and B cells. 
Values and changes from randomization in serum and biochemical 
markers of tumor progression. 
Values and changes from randomization in Her-2-specific 
antibodies (IgG) inhibition of in-vitro tumor cell growth. 
Values and changes from randomization in intra-tumor T cells and 
biochemical markers from pre- and post- treatment tumor biopsies. 
Phase 2 Safety Endpoints: 
Incidence of treatment-emergent adverse events (TEAEs), Grade 
3 / 4 / 5 TEAEs, serious adverse events (SAEs), and TEAEs 
leading to study treatment discontinuation. 
Incidence of treatment-emergent Grade 3 / 4 clinical laboratory 
abnormalities. 
Changes and shifts from randomization in clinical laboratory, vital 
signs, and electrocardiogram (ECG) parameters. 
Change from randomization in ECOG performance grade. 
Concomitant medication use. 
Treatment compliance. 
Phase 2 Dose Escalation Primary Endpoint: 
The safety and tolerability of IMU-131 will be evaluated by 
adverse events (AEs) and laboratory measurements. AEs and 
laboratory abnormalities will be graded by Common Terminology 
Criteria for Adverse Events (CTCAE) v5.0 including: 
-
Incidence of treatment-emergent adverse events (TEAEs),
Grade 3 / 4 / 5 TEAEs, serious adverse events (SAEs), and
TEAEs leading to study treatment discontinuation.
-
Incidence of treatment-emergent Grade 3 / 4 clinical
laboratory abnormalities.
-
Changes and shifts in clinical laboratory, vital signs, and
electrocardiogram (ECG) parameters.
Phase 2 Dose Escalation Secondary Endpoints: 
OS measured from enrollment to death due to any cause. 
PFS measured from enrollment to date of earliest progressive 


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disease (PD) based on Investigator disease assessment according 
to RECIST 1.1 criteria, or to date of death from any cause. 
TTP measured from enrollment to date of earliest PD based on 
Investigator disease assessment according to RECIST 1.1 criteria. 
ORR measured from enrollment as the proportion of patients 
achieving a confirmed best overall response of CR or PR based on 
Investigator disease assessment according to RECIST 1.1 criteria. 
DOR measured from enrollment to when earliest CR or PR is 
observed to PD or death due to any cause based on Investigator 
disease assessment according to RECIST 1.1 criteria. 
DCR measured from enrollment as the proportion of patients 
achieving a confirmed best overall response of complete response 
(CR), partial response (PR) or stable disease (SD) based on 
Investigator disease assessment according to RECIST 1.1 criteria. 
Percentage CTS measured from enrollment as the sum of 
diameters based on Investigator disease assessment according to 
RECIST 1.1 criteria. 
Phase 2 Dose Escalation Exploratory Endpoints: 
Values and changes from enrollment in humoral and cellular 
immunogenicity data including P467-specific antibodies (IgG), 
Her-2-specific antibodies (IgG), vaccine-specific cytokine levels 
and regulatory and effector T and B cells. 
Values and changes from enrollment in serum and biochemical 
markers of tumor progression. 
Values and changes from enrollment in Her-2-specific antibodies 
(IgG) inhibition of in-vitro tumor cell growth. 
Values and changes from enrollment in intra-tumor T cells and 
biochemical markers from pre- and post- treatment tumor biopsies. 
Study Design 
This protocol has a 2-part design. 
Part 1 consists of Phase 1b: Dose Escalation 
Phase 1b is an open-label, single arm, dose escalation study to evaluate 
safety, tolerability and immunogenicity and to assess the RP2D of IMU- 
131 initiated 14 days prior to the start of chemotherapy. All patients 
entering the Phase 1b study will receive IMU-131 and chemotherapy. 
RP2D is defined as the dose resulting in the best safety/tolerability and 
immunology results and will be determined after all dose cohorts have 
completed Day 56 of the study and an interim analysis of the Phase 1b 
data has been conducted by the Cohort Review Committee (CRC). 
Phase 1b Long Term Maintenance (LTM) 
Within Phase 1b there is provision for patients to continue on IMU-131 
as long-term maintenance. Patients completing the Day 56/End of 


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Treatment Visit for Phase 1b will be maintained on booster doses of IMU- 
131 starting from Day 98. 
Duration of treatment in Phase 1b 
Each patient will be administered 3 injections of IMU-131 (P467- 
CRM197-Montanide emulsion), at a single dose level on Days 0, 14, and 
35, accompanied by chemotherapy cycles every 21 days starting from Day 
14. Chemotherapy will be ceased by the investigator when clinically
indicated for the care of the patient. Patients will be discontinued from the
study and cease IMU-131 vaccinations when there is documented
evidence of disease progression according to the Response Evaluation
Criteria In Solid Tumors (RECIST 1.1) or if unacceptable toxicity occurs
(see Section 6.5 Patient Withdrawal for complete discontinuation criteria).
Part 2 consists of Phase 2: Evaluation of exploratory clinical activity of 
IMU-131 
Phase 2 will enroll approximately 36 patients and be conducted in the 
same centers with the addition of new centers, as required, to fulfill 
recruitment. Phase 2 will have similar inclusion/exclusion criteria and be 
conducted according to a similar schedule of events and study procedures. 
During conduct of the Phase 1b study and prior to the start of Phase 2, an 
amendment to the current protocol will be submitted for ethical and 
regulatory review. The Phase 2 evaluation of clinical activity of IMU- 
131 will be initiated after approval of Phase 2 and upon completion of 
Phase 1b (all cohorts completed through Day 56 and selection of a RP2D 
of IMU-131). 
Phase 2 is an open-label randomized comparison of IMU-131 plus 
standard of care chemotherapy versus standard of care chemotherapy 
alone. Patients will be randomly assigned to either ‘IMU-131 plus 
chemotherapy’ or ‘chemotherapy alone’ groups. Treatment for both 
groups will begin at the Baseline/Day 0 visit. 
The IMU-131 plus chemotherapy group will receive vaccination of IMU- 
131 at Baseline/Day 0, Day 14, Day 35, Day 77, Day 140 and then every 
63 days until disease progression. 
Both the IMU-131 plus chemotherapy group and the chemotherapy alone 
group will receive chemotherapy starting at the Baseline/Day 0 Visit and 
then every 21 days for a maximum of 6 cycles as clinically indicated or 
until disease progression, whichever occurs sooner. 
Phase 2 Extension 
Dose escalation during Phase 2 is an open-label, multicenter, single arm 
dose escalation study with the same inclusion/exclusion criteria as Phase 
2 and the same schedule of assessments (SoA) as Phase 2 IMU- 
131+chemotherapy arm. Patients will no longer be followed for post 
treatment follow up. The safety of each dose will be assessed by CRC 
after at least 3 patients have 3 doses of IMU-131 and one cycle of 
chemotherapy and have completed the 35 day DLT window. Two dose 
-131, will


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further characterize the safety, immunogenicity, and clinical activity of 
IMU-131 in combination with chemotherapy. 
The Sponsor may close the study once the last patient completes the end 
of treatment visit. 
Population 
The phase1b/2 protocol is a multicenter study. Phase 1b will enroll up to 
a maximum of 18 patients, Phase 2 will enroll approximately 36 patients, 
and Phase 2 dose escalation will enroll up to 20 patients diagnosed with 
advanced/metastatic, HER2/neu overexpressing, gastric or GEJ 
adenocarcinoma who meet all inclusion criteria and no exclusion criteria. 
The Phase 2 extension dose escalation study will be conducted at sites in 
Georgia, Ukraine, and Serbia. 
Phase 2 
Randomization 
and Blinding 
In Phase 2, patients who are determined to be eligible for the study will 
be randomized on their Baseline/Day 0 Visit. Patients will be allocated to 
receive IMU-131 plus chemotherapy or chemotherapy only in a 1:1 ratio. 
Randomization will be performed centrally and stratified by tumor stage 
at screening (III vs IV). 
Patients will be randomized into this open-label study using an Interactive 
Voice or Web Response System (IxRS). The central radiography review 
will be blinded. The rules describing the distribution of data and results 
will be documented prior to study commencement. 
Phase 2 Extension: dose escalation in Phase 2 is open label and non- 
randomized with patients entering the study sequentially according to the 
dose level being studied. 
Sample size and 
sample size 
determination 


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PFS will be assessed as a secondary outcome with an analysis following 
24 evaluable progression events coded using RESIST 1.1 with patients 
not having a progression being censored at the time of last evaluation for 
progression or counted as a progression event if death is within 42 days 
of last evaluation for progression. 
Assumptions of accrual time, loss to follow-up, and pooled event rate 
(both arms combined) used in the sample size calculations may be 
monitored. The number of patients enrolled, and duration of enrolment 
and follow-up may be adjusted to achieve the planned number of events 
at the time of the final analysis of the primary endpoint. 
Phase 2 Extension: Phase 2 dose escalation will enroll up to 20 patients. 
No formal statistical calculation of sample size will be used for the Phase 
2 dose escalation. The sample size is empirical and based on a standard 
3+3 dose escalation design with expansion of up to 10 patients per dose 
escalation cohort. 
Safety Monitoring Phase 1b: 
Cohort Review Committee (CRC) 
Prior to enrollment of patients into the Phase 1b study, a CRC, comprising 
relevant site investigators, the Medical Monitor, and Sponsor 
representatives, will oversee safety, cohort evaluation and dose-escalation 
for the study. A formal charter which will establish the rules, meeting 
frequency and scope of responsibilities of the CRC will be established for 
the conduct of the CRC. 
Dose Escalation within Phase 1b 
There will be up to 6 patients in each cohort in Phase 1b. The CRC will 
review data from one complete cycle of chemotherapy (including 3 doses 


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of IMU-131, on Days 0, 14, and 35) for at least 3 patients in a dose cohort 
to authorize dose escalation. 
A staggered enrollment will be used for patient safety, whereby a dose 
cohort must be completed and reviewed by the CRC before further 
recruitment. The decision whether to escalate to the next dose cohort will 
be made by the CRC when at least 3 patients in the current dose cohort 
have completed chemotherapy cycle 1 (35 days of the study, including 3 
doses of IMU-131 on Days 0,14 and 35). 
Phase 1b dose escalation will involve 3 dose levels of IMU-131 with a 
standard 3+3 scheme for determination of safety prior to dose escalation. 
Patients will receive 3 doses of IMU-131 (Days 0, 14 and 35) with 
chemotherapy being initiated 14 days after the first dose of IMU-131 with 
evaluation occurring after the first 21-day cycle of chemotherapy and 
before opening the enrollment to the next higher dose cohort. 
Dose Escalation Decision Rules 
If 0 out of 3 patients with treatment related dose-limiting toxicity 
(DLT) at a given IMU-131 dose level, enter 3 patients at the next 
dose level (DLT: a drug-related Grade 3 toxicity that cannot be 
resolved to a Grade 1 with appropriate therapy within 2 weeks, 
or a Grade 4 or greater toxicity graded by CTCAE v4.03, related 
to the IMU-131 vaccine). 
related DLT at a given dose 
level, dose escalation will be stopped. This dose level will be 
declared the maximally administered dose (highest dose 
administered). Three (3) additional patients will be entered at the 
next lower dose level if only 3 patients were treated previously 
at that dose 
If 1 out of 3 patients with treatment related DLT at a given dose 
level, enter at least 3 more patients at this dose level. If 0 of these 
3 patients experience treatment related DLT, proceed to the next 
dose level. If 1 or more of this group suffer treatment related 
DLT, then dose escalation is stopped, and this dose is declared 
the maximally administered dose. Three (3) additional patients 
may be entered at a dose between the current dose and the next 
lowest dose level, the exact dose of which will be determined by 
the CRC. 
Phase 2 
The Independent Data Monitoring Committee (IDMC) will be scheduled 
to meet after 8, 16 and 24 progression events occur and at intervals no less 
than once per year. Further details of the IDMC meetings and review 
procedures will be contained in the IDMC charter. 
Phase 2 Extension 
Dose Escalation within Phase 2 
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cohort for safety evaluation by CRC prior to next dose being opened to 
enrollment. The CRC will review data from one complete cycle of 
chemotherapy and 3 doses of IMU-131, for at least 3 patients in a dose 
cohort to authorize dose escalation. The DLT window is 35 days. 
Dose escalation in Phase 2 will start at 
 IMU-131, within a standard 
3 + 3 scheme for determination of safety prior to opening enrollment to 
the 
 IMU-131 dose cohort. A dose cohort must be reviewed by CRC 
for DLTs according to dose escalation decision rules before opening the 
next dosed cohort. 
Either the 
 or 
 dose escalation cohort may be expanded up to 
10 patients after CRC clearance of the 35-day DLT period. 
Phase 2 Dose-limiting Toxicity Definition 
A dose limiting toxicity (DLT) is defined as an IMU-131-related Grade 3 
toxicity that cannot be resolved to a Grade 1 with appropriate therapy within 
2 weeks, or a Grade 4 or greater toxicity graded by CTCAE v5.0, related to 
the IMU-131 vaccine. 
In addition, after enrollment in Phase 2 dose escalation begins, the CRC will 
meet by teleconference as soon as feasible after any of the following occur 
to determine if the criteria for dose limiting toxicity (DLT) has been met: 
One or more patients experience a serious adverse reaction assessed 
as related to the vaccine by the investigator. 
 One or more patients experience anaphylaxis. 
Phase 2 Dose Escalation Decision Rules 
Dose escalation within Phase 2 will follow the same dose escalation rules 
and CRC review process as Phase 1b. 
A dose limiting toxicity (DLT) is defined as an IMU-131-related 
Grade 3 toxicity that cannot be resolved to a Grade 1 with appropriate 
therapy within 2 weeks, or a Grade 4 or greater toxicity graded by 
CTCAE v5.0, related to the IMU-131 vaccine. 
In addition, after enrollment in Phase 2 dose escalation begins, the 
CRC will meet by teleconference as soon as feasible after any of the 
following occur to determine if the criteria for dose limiting toxicity 
(DLT) has been met: 
One or more patients experience a serious adverse reaction assessed 
as related to the vaccine by the investigator. 
 One or more patients experience anaphylaxis. 
Phase 2 Dose Escalation Decision Rules 
Dose escalation within Phase 2 will follow the same dose escalation 
rules and CRC review process as Phase 1b. 


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Statistical 
Analysis 
Inclusion Criteria Patients must meet all the following inclusion criteria to be eligible for 
enrollment into the study: 
1. Patient has been informed of the investigational nature of this
study and has given written informed consent in accordance with
institutional, local, and national guidelines;
2. Age  20 years old; 
3. Life expectancy of at least 12 weeks;
4. Phase 1b: No prior chemotherapy or radiotherapy for advanced
gastric or GEJ cancer within 6 months prior to Day 0;
Phase 2/Phase 2 Extension: No prior chemotherapy or
radiotherapy for advanced gastric or GEJ cancer within 3 months
prior to Day 0;


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5. Metastatic gastric or GEJ adenocarcinoma, or locally advanced
disease not amenable to surgical resection;
6. HER2/neu overexpression (3+ by immunohistochemistry (IHC)
or if IHC 2+ confirmed by fluorescent in situ hybridization
[FISH], brightfield double in situ hybridization [BDISH] or
chromogenic in situ hybridization [CISH]). Patients with IHC 2+
expression without confirmation of overexpression by fluorescent
in situ hybridization [FISH], BDISH or chromogenic in situ
hybridization [CISH]) may be included in Phase 1b with
agreement of Imugene Limited;
7. Phase 1b: ECOG performance status 0–1;
Phase 2/Phase 2 Extension: ECOG performance status 0–2;
8. At least one measurable lesion as defined by RECIST 1.1 criteria.
Patients with non-measurable lesions may be included in Phase1b
with agreement of Imugene Limited;
9. Adequate left ventricular ejection function at baseline, defined as
LVEF > 50% by echocardiogram or MUGA scan (Multi Gated
Acquisition Scan);
10. Adequate hematologic function: absolute neutrophil count (ANC)
1.5 x 109/L, platelet count  100 x 109/L, and hemoglobin
g/dL; 
11. Adequate liver function evidenced by bilirubin
 1.5 x laboratory 
upper limit of normal [ULN], and ALT and AST  3 x laboratory 
ULN if no liver involvement or ALT and AST  5 times laboratory 
ULN with liver involvement; 
12. Adequate renal function (creatinine
 1.5 x laboratory ULN); 
13. Willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
14. Male and female patients of childbearing potential must agree to
use a highly effective method of contraception throughout the
study and for at least 28 days following chemotherapy or 180
days after the last dose of IMU-131 (see Section 4.3 for details). A
patient is of childbearing potential if, in the opinion of the
investigator, he/she is biologically capable of having children and
is sexually active.
Exclusion Criteria Patients presenting with any of the following will not be included in the 
study: 
1. Previous treatment with trastuzumab or any other HER2/neu
targeting antibody or agent;
2. Continuous systemic treatment with either corticosteroids (>10
mg daily prednisone equivalents) or other immunosuppressive
medications within 4 weeks prior to first dose of study treatment.


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Inhaled or topical steroids and physiological replacement doses of 
up to 10 mg daily prednisone equivalents are permitted in the 
absence of active auto-immune disease; 
3. Prior organ transplant;
4. Phase 1b: Patient not considered a candidate for 5-FU,
capecitabine, or cisplatin chemotherapy;
Phase 2/Phase 2 Extension: Patient not considered a candidate
for 5-FU, capecitabine, cisplatin or oxaliplatin chemotherapy;
5. History of documented congestive heart failure; angina pectoris
requiring antianginal medication; evidence of transmural
infarction on ECG; poorly controlled hypertension; clinically
significant valvular heart disease; high risk uncontrolled
arrhythmias; or New York Heart Association (NYHA) class II
heart disease;
6. If on warfarin (Coumadin®) or other vitamin K antagonists;
7. Concurrent active malignancy except for adequately controlled
limited basal cell carcinoma of the skin;
8. Peripheral neuropathy or hearing loss of NCI CTCAE Grade > 2;
9. History of uncontrolled seizures, central nervous disorders or
psychiatric disability judged by the investigator to be clinically
significant and precluding informed consent, participation in the
study, or adversely affecting compliance to study drugs;
10. Active infection requiring IV antibiotics;
11. Positive for human immunodeficiency virus (HIV) (HIV 1/2
antibodies) or active hepatitis B (HBsAg reactive) or active
hepatitis C (HCV ribonucleic acid [RNA] qualitative) infection;
12. Pregnant or lactating females;
13. Major surgery within 4 weeks prior to study entry. Minor surgery 
(excluding diagnostic biopsy) within 1 week prior to study entry;
14. Has received a live-virus vaccination within 4 weeks of first study
vaccination. Seasonal flu vaccines that do not contain live virus
are permitted;
15. Current or recent (within 4 weeks of first IMU-131 vaccination)
treatment with another investigational drug or participation in
another investigational study.
16. Phase 2/Phase 2 Extension: Patients with a known diphtheria
toxoid hypersensitivity. 
Study 
drugs/Dosage 
forms/Routes 
The investigational product, IMU-131, will be supplied as P467-CRM197 
(aqueous phase vaccine) and Montanide ISA 51 VG (adjuvant) in separate 
boxes. Each box of P467-
phase vaccine in 1 mL PBS buffer, two vial adapters, two luer-lock 
syringes, one dosing syringe and needle and one I connector. Each box of 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 30 of 121 
CONFIDENTIAL 
Montanide contains a single 3 mL vial of Montanide ISA 51 VG. 
IMU-131 vaccine for IM administration to be prepared by the study 
pharmacist or study site personal on the day of injection 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
In Phase 1b, the IMU-131 vaccine will be administered IM into the deltoid 
region of the upper arm with a 0.60 x 25 mm 23G needle on Days 0, 14 
and 35. 
In Phase 2, the IMU-131 vaccine will be administered IM into the deltoid 
region of the upper arm with a 0.60 x 25 mm 23G needle on Days 0, 14, 
35, 77, 140 and then every 63 days. 
In Phase 2 Extension, the IMU-131 vaccine will be administered at doses 
of either 
 or 
 IM into the deltoid region of the upper arm with 
a 25-38mm (1-1.5 inches), 21-23G needle on Days 0, 14, 35, 77, 140 and 
then every 63 days. 
Storage conditions for Investigational Product: 
a) IMU-131 in aqueous phase will be stored at < -15oC until required.
b) Montanide will be stored at +2 - +8oC until required.
In Phase 1b, chemotherapy will be prepared and dispensed according to 
Pharmacy standard practice. Chemotherapy will include the following 
treatments: 
cisplatin, IV (80 mg/m2) and either; 
5-FU, 4000 mg/m2 continuous infusion;
or capecitabine, 2000 mg/m2/day, orally.
In Phase 2 and Phase 2 Extension, chemotherapy will be prepared and 
dispensed according to Pharmacy standard practice. Chemotherapy will 
include the following treatments: 
cisplatin, 80 mg/m2, IV and either; 
5-FU, 4000 mg/m2 continuous infusion;
or capecitabine, 2000 mg/m2/day, orally.
Or oxaliplatin, 130 mg/m2, IV and capecitabine, 2000 mg/m2/day, 
orally. 
Dose and 
Schedule 
Phase 1b 
IMU-131 
A total of 3 injections of IMU-131-Montanide emulsion (IMU-131) at a 
particular dose will be given to patients in the Phase 1b study (on Days 0, 
14, and 35), with chemotherapy cycles every 21 days starting from Day 14. 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 31 of 121 
CONFIDENTIAL 
IMU-131 is formulated into either a low, medium or high dose with the 
concentration of each dose remaining constant while the injection volume 
varies: 
Low dose: 10 
 (peptide P467 antigen equivalent) P467-CRM197 in 
50 µL PBS buffer and 50 µL Montanide ISA 51 Sterile adjuvant resulting 
in a 0.1mL injection volume; 
Mid dose: 30 
 (peptide P467 antigen equivalent) P467-CRM197 in 
150 µL PBS buffer and 150 µL Montanide ISA 51 Sterile adjuvant 
resulting in a 0.3mL injection volume or; 
High dose: 
-CRM197 in 
250 µL PBS buffer and 250 µL Montanide ISA 51 Sterile adjuvant 
resulting in a 0.5mL injection volume. 
Patients will be enrolled in cohorts of up to 6 patients at 1 of 3 escalating 
dose levels of IMU-131: 
Cohort 1 - 10 µg as a 0.1 mL injection 
Cohort 2 - 30 µg as a 0.3 mL injection 
Cohort 3 - 50 µg as a 0.5 mL injection 
Chemotherapy 
Chemotherapy will include the following treatments, the dose and 
duration of which may be varied by the investigator as clinically indicated 
for the patient: 
Chemotherapy will be administered to all patients as a 21-day regimen 
starting 14 days (+ or – 1 day) after first IMU-131 vaccination: cisplatin, 
IV (80 mg/m2 on Day 14, then every 21 days) and either 5-FU, 
4000 mg/m2 CIV (administered as 1000 mg/m2/day as continuous 
infusion for 96 hours on days 14 to 17, then every 21 days) or capecitabine 
for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice 
daily morning and evening for a total of 2000 mg/m2/day on days 14 to 
27, then every 21 days). 
Chemotherapy will be administered in 21-day cycles as tolerated or for 
any other reason to discontinue chemotherapy treatment as determined by 
the investigator for the clinical care of the patient. 
Phase 2 
IMU-131 
Injections of IMU-131-Montanide emulsion (IMU-
given to patients in the ‘IMU-131 plus chemotherapy’ group in the Phase 
2 study on Days 0, 14, 35, 77, 140 and then every 63 days. 
Phase 2 Extension 
IMU-131 
A total of 3 injections of IMU-131-Montanide emulsion (IMU-131) at a 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 32 of 121 
CONFIDENTIAL 
particular dose will be given to patients in the Phase 2 dose escalation 
study on Days 0, 14, and 35, and then every 63 days with chemotherapy 
cycles every 21 days (to a maximum of 6 cycles) starting from Day 0.  
IMU-
L injection volume 
-CRM197 in
500 µL PBS buffer with 500 µL Montanide ISA 51 sterile adjuvant 
resulting in a 1.0 mL injection volume. 
Cohort 1 – 100 µg 
Cohort 2 – 200 µg Refer to the study pharmacy manual for detailed IMU- 
131 vaccine preparation and administration instructions. 
Chemotherapy in Phase 2 and Phase 2 Extension 
Chemotherapy will include the following treatments, the dose and 
duration of which may be varied by the investigator as clinically indicated 
for the patient. 
Chemotherapy will be administered to all patients as a 21-day regimen 
starting at Day 0 and consisting of: cisplatin by intravenous administration 
at 80 mg/m2 on the first day of each cycle and either 5-FU, 4000 mg/m2 
CIV (administered as 1000 mg/m2/day as continuous infusion for 96 hours 
on days 1 to 4 of each cycle) or capecitabine for 14 days at 2000 
mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and 
evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle), or 
oxaliplatin, by intravenous administration at 130 mg/m2 on Day 1 of each 
cycle and capecitabine for 14 days at 2000 mg/m2/day, orally 
(administered as 1000 mg/m2 twice daily morning and evening for a total 
of 2000 mg/m2/day on days 1 to 14 of each cycle). 
Chemotherapy will be administered in 21-day cycles as tolerated to a 
maximum of 6 cycles. One or more chemotherapy treatments may be 
varied by dose, frequency or discontinued completely as determined by 
the investigator for the clinical care of the patient. 
Phase 1b Study 
Procedures 
Physical Examination (Screening, Days 0, 14, 35, 56, 77, 98, LTM 
visits) 
The physical examination will include an evaluation of body systems (e.g. 
cardiovascular, gastrointestinal, neurological, head and neck, respiratory, 
dermatology). 
Height, Weight and Vital Signs (Screening, Days 0, 14, 35, 56, 77, 98, 
LTM visits) 
Body height (at screening visit only), weight, and vital signs (blood 
pressure, pulse and temperature) will be measured. 
Radiographic Assessment (Screening, Days 56, 98, LTM visits) 
For all patients, a radiographic assessment will be performed at Screening 
(for inclusion criteria assessment), and at Day 56, Day 98 and at long term 
maintenance visits until disease progression. 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 33 of 121 
CONFIDENTIAL 
Assessment of the tumor will include evaluation according to the 
Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1). 
Cardiac Assessment (Screening, Day 56) 
Cardiac assessment of suitability for inclusion in the study and on Day 56 
will be performed by the study investigator and be based on assessment of 
medical history, physical examination, 12-lead ECG results and evaluation 
of left ventricular ejection fraction (LVEF) by echocardiography or 
MUGA scan. 
Laboratory Assessments 
Hematology and serum chemistry analyses will be performed by an 
accredited central laboratory. Immunological analysis will be performed 
by an accredited specialist immunology laboratory. 
a) Safety Laboratory Assessments (Screening, Days 0, 14, 35, 56, 77, 
98, LTM visits)
Blood samples of approximately 10 mL per visit for the assessment of 
hematological and serum chemistry parameters will be collected and 
processed in accordance with the central laboratory study manual. 
Safety laboratory panels are defined as follows: 
Human immunodeficiency virus (HIV 1/2 antibodies), hepatitis B 
(HBsAg reactive) and hepatitis C (HCV ribonucleic acid [RNA] 
qualitative) (at screening only). 
Hematology: Hematology to include CBC, including RBC count, 
hemoglobin, hematocrit, reticulocyte count, WBC count with differential 
(neutrophils, bands, eosinophils, basophils, lymphocytes, monocytes, and 
other cells), platelet count, C-reactive protein (CRP). 
Serum Chemistry: BUN or urea, creatinine, sodium, chloride, potassium, 
magnesium, bicarbonate, calcium, phosphorus, total protein, albumin, 
alkaline phosphatase, glucose, total bilirubin, direct and indirect bilirubin, 
lactate dehydrogenase (LDH), cholesterol, uric acid, triglyceride levels, 
gamma glutamyl transpeptidase (GGT), AST, and ALT. 
b) Immunologic Assessments (Screening, Days 0, 14, 35, 56, 77, 98,
LTM visits)
Prior to each vaccination a 1 x 8 mL whole blood sample for humoral 
immunity will be obtained from the patient at Days 0, 14, 35, 56, 77, 98 
and at LTM visits. Additionally, on Days 0, 56 and at each LTM visit, 5 
x 8 mL heparinized blood samples will be collected for peripheral blood 
mononuclear cell (PBMC) isolation and analysis of cellular parameters. 
HER2/neu overexpression (Screening) 
Confirmation of HER2/neu overexpression is required for inclusion in 
this study. However, patients with IHC HER2 ++ expression without 
confirmation of overexpression by fluorescent in situ hybridization 
[FISH], brightfield double in situ hybridization [BDISH] or chromogenic 
in situ hybridization [CISH]) may be included in Phase 1b with agreement 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 34 of 121 
CONFIDENTIAL 
of Imugene Limited. 
A previous pathology result confirming HER2/neu overexpression is 
acceptable. If analysis of a tumor biopsy is required for confirmation of 
HER2/neu overexpression then this may be achieved via analysis of a 
fresh or archived tissue sample. 
If a biopsy sample is used to determine HER2/neu overexpression then 
analysis of intra-tumor T cells for CD8+, CD4+, Th1, Th2, Tregs (Foxp3+ 
CD25+) will also be performed if these analyses are available at the 
pathology lab conducting HER2/neu overexpression analysis. 
HER2/neu analysis will be conducted at each centre’s local pathology 
laboratory by immunohistochemistry (IHC) and fluorescent in situ 
hybridization [FISH], brightfield double in situ hybridization [BDISH] or 
chromogenic in situ hybridization [CISH] if IHC result is equivocal. 
Using the IHC method an unequivocal result of HER2 overexpression is 
defined as HER2 +++, an equivocal result is defined as HER2 ++, and a 
negative result is defined as HER2 +. If equivocal result (IHC HER2 ++) 
then additional analysis via FISH, BDISH or CISH will be conducted for 
confirmation of HER2 overexpression. The definition of FISH, BDISH or 
CISH positivity in gastric or gastro–esophageal junction cancer is a 
ECOG performance grade (Screening) 
The ECOG performance grade for screening evaluation should be 
determined using the criteria defined in Appendix 3: ECOG Performance 
Status Scale. 
Vaccination site evaluation (Days 2, 16, 37) 
The purpose of vaccination site evaluation is to determine the nature and 
frequency of local/vaccination site reactions. The vaccination site should 
be evaluated for local effects of the vaccine injection including pain, 
tenderness; erythema/redness and swelling/induration (see Section 9.7.1 
Local (injection site) Adverse Event Intensity for further details). All local 
vaccination site effects are to be reported in the CRF and graded according 
to Table 4: Grading of Local Adverse Event Intensity presented in Section 
9.7.1. 
Photographs will be taken during vaccination site evaluation if there are 
visible local injection site reactions. 
Pregnancy Test (Screening, Days 0, 14, 35, 98, LTM visits) 
For female patients of childbearing potential, a urine pregnancy test, with 
sensitivity of at least 25 mIU/mL, will be performed immediately before 
administration of each vaccine dose. A negative pregnancy test result is 
required before the patient may receive the investigational product. If urine 
pregnancy test is positive then confirmation of pregnancy will be by BHCG 
blood test. If BHCG blood test is negative then vaccination schedule may 
resume. 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 35 of 121 
CONFIDENTIAL 
Phase 2 and 
Phase 2 Extension 
Study Procedures 
Physical Examination (Screening, Baseline, Days 21, 42, 63, 84, 105, 
126 then every 42 days and EoT visit) 
The physical examination will include an evaluation of body systems (e.g. 
cardiovascular, gastrointestinal, neurological, head and neck, respiratory, 
dermatology). After the Baseline physical examination, a symptom- 
directed physical examination is allowed at subsequent visits at the 
investigator’s discretion. 
Height, Weight, Vital Signs, Concomitant Medications, Concomitant 
Procedures and Adverse Events (at each study visit, excluding post- 
treatment follow-up visits) 
Body height (at screening visit only), weight, and vital signs (blood 
pressure, pulse and temperature) will be measured and concomitant 
medications, concomitant procedures and adverse events will be 
documented. 
Radiographic Assessment (Baseline, Days 42, 84, 126 then every 42 
days) 
For all patients, a radiographic assessment will be performed at Baseline 
(assessment allowed up to 14 days before Baseline Visit), Days 42, 84, 
126 then every 42 days until disease progression. Assessment of the tumor 
will include evaluation according to RECIST 1.1. 
In the Phase 2 extension, a repeat scan may be performed as an 
unscheduled visit at the investigator’s discretion to confirm progression 
4-6 weeks after the date of the original scan indicating progression. If
progression is confirmed the original date of progression will be used for
disease assessment.
Cardiac Assessment (Screening, Day 84 then every 84 days and EoT 
visit) 
Cardiac assessment to be performed at Screening, on Day 84 then every 
84 days and at EoT visit. It will be performed by the study investigator 
and be based on assessment of medical history, physical examination, 12- 
lead ECG results and evaluation of left ventricular ejection fraction 
(LVEF) by echocardiography or MUGA scan. 
Laboratory Assessments 
Hematology and serum chemistry analyses will be performed by an 
accredited local laboratory. Analysis of vaccine-specific cytokine levels, 
in-vitro inhibition of tumor cell growth, intra-tumor T cell and biomarker 
analysis will be performed by an accredited central laboratory. Humoral 
and cellular immunological analysis will be performed by an accredited 
specialist central immunology laboratory. 
Unused blood /serum and/or tissue samples collected during the study 
from patients who have signed an appropriate informed consent form may 
be stored and used for future research.  The coded samples may be stored 
up to 15 years after the clinical study ends. A patient may contact the 
investigator to have their unused samples destroyed at any time during the 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 36 of 121 
CONFIDENTIAL 
storage period. Results from the future use studies will not be shared with 
patients. 
1) Safety Laboratory Assessments (Screening, Baseline, Days 21, 42,
63, 84, 105, 126 then every 42 days and EoT visit)
Blood samples of approximately 10 mL per visit for the assessment of 
hematological and serum chemistry parameters will be collected and 
processed in accordance with local laboratory procedures and reference 
ranges. 
Safety laboratory panels are defined as follows: 
Human immunodeficiency virus (HIV 1/2 antibodies), hepatitis B 
(HBsAg reactive) and hepatitis C (HCV ribonucleic acid [RNA] 
qualitative) (at screening only). 
Hematology: Hematology to include CBC, including RBC count, 
hemoglobin, hematocrit, reticulocyte count, WBC count with differential 
(neutrophils, bands, eosinophils, basophils, lymphocytes, monocytes, and 
other cells), platelet count, C-reactive protein (CRP). 
Serum Chemistry: BUN or urea, creatinine, sodium, chloride, potassium, 
magnesium, bicarbonate, calcium, phosphorus, total protein, albumin, 
alkaline phosphatase, glucose, total bilirubin, direct and indirect bilirubin, 
lactate dehydrogenase (LDH), cholesterol, uric acid, triglyceride levels, 
gamma glutamyl transpeptidase (GGT), AST, and ALT. 
2) Exploratory Endpoint Laboratory Assessments (Baseline, Days 84 
then every 84 days and EoT visit)
A 1 x 10 mL whole blood sample to assess vaccine-specific cytokine 
levels and in-vitro inhibition of tumor cell growth will be obtained from 
each patient at Days 0, 84 then every 84 days and at EoT visit. When 
vaccination with IMU-131 occurs, these samples will be taken prior to 
vaccination. 
3) Immunologic Assessments
a)
Humoral samples (Baseline, Days 21, 42, 63, 84, 126 then
every 42 days and EoT visit)
A 1 x 10 mL whole blood sample for humoral immunity will be obtained 
from each patient at Days 0, 21, 42, 63, 84, 126 then every 42 days and at 
EoT visit. When vaccination with IMU-131 occurs, these samples will be 
taken prior to vaccination. 
b)
Cellular samples (Screening [Phase 2 Extension only],
Baseline, Days 84 then every 84 days and EoT visit)
Collection of 40 mL blood sample will be performed for PBMC isolation 
and analysis of cellular parameters at Days 0, 84 then every 84 days and 
at EoT visit. When vaccination with IMU-131 occurs, these samples will 
be taken prior to vaccination. 
In Phase 2 Extension, an additional 40 mL blood sample will be 
performed for PBMC isolation and analysis of cellular parameters during 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 37 of 121 
CONFIDENTIAL 
screening visits after enrolment eligibility including HER2 over- 
expression is confirmed. 
HER2/neu overexpression (Screening) 
Confirmation of HER2/neu overexpression is required for inclusion in 
this study. 
A previous pathology result confirming HER2/neu overexpression is 
acceptable. If analysis of a tumor biopsy is required for confirmation of 
HER2/neu overexpression, then this may be achieved via analysis of a 
fresh or archived tissue sample. 
HER2/neu analysis will be conducted at each center’s local pathology 
laboratory by immunohistochemistry (IHC) and fluorescent in situ 
hybridization [FISH], brightfield double in situ hybridization [BDISH] or 
chromogenic in situ hybridization [CISH] if IHC result is equivocal. 
Using the IHC method an unequivocal result of HER2 overexpression is 
defined as HER2 +++, an equivocal result is defined as HER2 ++, and a 
negative result is defined as HER2 +. If equivocal result (IHC HER2 ++) 
then additional analysis via FISH, BDISH or CISH will be conducted for 
confirmation of HER2 overexpression. The definition of FISH, BDISH or 
CISH positivity in gastric or gastro–esophageal junction cancer is a 
ECOG performance grade (Screening, Baseline, Days 84 then every 
84 days and EoT visit) 
The ECOG performance grade should be determined using the criteria 
defined in Appendix 3: ECOG Performance Status Scale. 
Pregnancy Test (at each study visit, excluding post-treatment follow- 
up visits) 
For female patients of childbearing potential, a urine pregnancy test, with 
sensitivity of at least 25 mIU/mL, will be performed immediately before 
administration of each vaccine dose. A negative pregnancy test result is 
required before the patient may receive the investigational product. If 
urine pregnancy test is positive, then confirmation of pregnancy will be 
by local laboratory BHCG blood test. If BHCG blood test is negative, then 
vaccination schedule may resume. 
Intra-tumor analysis (Screening, Day 84 and post-progression) 
A screening visit or archival tumor biopsy sample will be obtained for all 
patients for intra-tumor analysis (unless HER2 status has been confirmed 
previously and archival tissue is not available). An optional Day 84 and 
post-progression tumor biopsy sample will be requested from patients. 
These samples will be analyzed for intra-tumor T cells and biochemical 
markers. The screening visit biopsy sample may also be used to determine 
HER2/neu overexpression. 
Unscheduled Visit 
Unscheduled visits may be conducted at any time during Phase 2 by the 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 38 of 121 
CONFIDENTIAL 
investigator if clinically indicated for the care of the patient. 
An unscheduled visit may include any of the protocol required 
assessments listed in Section 8: Phase 2 Assessments. The exact 
assessments conducted at the unscheduled visit will be specified by the 
investigator and recorded in the CRF. Additional tests and procedures 
may be performed at the unscheduled visit for the clinical care of the 
patient after discussion with, and agreement of, the medical monitor. 
Phase 2 Only - Post-treatment Follow Up (FU) Visit (Every 42 days 
after EoT visit) After disease progression, anti-cancer therapy and 
survival information will be collected every 6 weeks until death, 
withdrawal or end of trial. Anti-cancer therapy and survival information 
may be collected more frequently than every 6 weeks for quality control 
and data cleaning purposes. After discontinuation from the study for any 
reason other than disease progression, radiographic change will be 
collected every 6 weeks until determination of progressive disease. 
All patients will be followed for radiographic change until determination 
of progressive disease and survival information and anti-cancer treatment 
until death, unless the patient requests to be withdrawn from radiographic 
change assessment and survival follow-up contact or the trial ends. 
Requests for withdrawal must be documented in the source documents and 
signed by the investigator. 
Phase 2 extension patients will no longer complete post-treatment follow 
up visits.  


The Schedule of Activities table provides an overview of the protocol visits and procedures. Refer to Study Procedures (Section 6) and Assessments 
(Section 7 for Phase 1b and Section 8 for Phase 2 and Phase 2 Extension) for detailed information on each procedure and assessment required for 
compliance with the protocol. 
h
f
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Investigational Product: 
Protocol Identifier: 
IMU-131 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
SCHEDULE OF ACTIVITIES 
Table 1: 
Schedule of Activities Phase lb 
Dose 1 
Dose2 
Dose 3 Period 
End of Treatment 
Screen 
Period 
Period(+/-
(+/- 3d) 
Visit 
3d) 
(+/- 3d) 
Study Days 
-2ld to -Id 
0 
2 
14 
16 
35 
37 
56 
IMU-131 Vaccination 
X 
X 
X 
Chemotherapy 
X 
X 
X 
Informed Consent 
X 
Demographics and prior medications 
X 
Medical History 
X 
Cancer History 
X 
Physical Exam 
X 
X 
X 
X 
X 
Weight and vital signs (temp, BP, pulse) 
X 
X 
X 
X 
X 
Height 
X 
Vaccination Site Evaluation/local effects 
X 
X 
X 
ECOG performance status 
X 
Radiographic Assessment 
X 
X 
IMUGENE LIMITED 
CONFIDENTIAL 
Chemoonly 
Start oflong term 
Follow-up Post-
Visit 
maintenance 
Withdrawal Visit 
(+/- 7d) 
(+/- 7d) 
(-2d, +16d) 
77 
98 
30 - 40 days after last 
vac 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Page 39 of 121 


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a
b
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Investigational Product: 
Protocol Identifier: 
Protocol Version: 
Study Days 
Cardiac Assessment 
Tumor biopsy for HER2 analysis 
Urine Pregnancy Test 
HIV, Hepatitis 
Hematology, Chemistry 
Immunology 
Concomitant Medications 
Concomitant Procedures 
Adverse Events (by interview with 
patient) 
IMUGENE LIMITED 
IMU-131 
IMU.ACS.001 
Protocol Global Amendment #5, 27 September 2023 
Dose 1 
Dose2 
Dose 3 Period 
End of Treatment 
Screen 
Period 
Period(+/-
(+/- 3d) 
Visit 
3d) 
(+/- 3d) 
-2ld to -Id 
0 
2 
14 
16 
35 
37 
56 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CONFIDENTIAL 
Chemoonly 
Start oflong term 
Follow-up Post-
Visit 
maintenance 
Withdrawal Visit 
(+/- 7d) 
(+/- 7d) 
(-2d, + 16d) 
77 
98 
30 - 40 days after last 
vac 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Page 40 of 121 


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b
c 
e 
Footnotes for Schedule of Activities – Phase 1b and Long Term Maintenance 
Investigational Product: 
Protocol Identifier: 
IMU-131 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
Table 2: 
Schedule of Activities Long Term Maintenance 
Start of Long Term 
LTM 
LTM 
LTM 
Maintenance (LTM) 
Visit 1 
Visit2 
Continuing 
(+/-7d) 
(+/-14d) 
(+/-14d) 
(+/- 14d) 
Study Days 
98 
182 
266 
Every 84 days 
IMU-131 Vaccination 
X 
X 
X 
X 
Chemotherapy 
X 
Day 98 then every 21 days until chemotherapy is ceased 
(lfnot ceased in Phase lb) 
Physical Exam including weight and vital signs (temp, 
X 
X 
X 
X 
BP, pulse) 
Radiographic Assessment 
X 
X 
X 
X 
!Urine Pregnancy Test 
X 
X 
X 
X 
!Hematology, Chemistry 
X 
X 
X 
X 
Immunology 
X 
X 
X 
X 
Concomitant Treatments 
X 
X 
X 
X 
[Adverse Events (by interview with patient) 
X 
X 
X 
X 
Follow-up Post-
Withdrawal Visit 
(-2d, +16d) 
30 - 40 days after last 
vac 
X 
X 
X 
X 
Negative urine pregnancy test required for women of childbearing potential at screening and prior to each vaccination. If positive urine test vaccination may be delayed 
until negative BHCG blood test. 
b 
Hematology and serum chemistry to be performed at Screening, Days 0, 14, 35, 56, 77, 98 and at each LTM visit. 
1 x 8 mL (i.e. 1 tube) whole blood sample for humoral immunity on days 0, 14, 35, 56, 77, 98, and each LTM visit and 5 x 8 mL heparinized blood on days 0, 56 and 
each L TM visit for cellular immunity. To be taken prior to vaccination at vaccination visits, including during long term maintenance. 
IMUGENE LIMITED 
Page 41 of 121 
CONFIDENTIAL 


Investigational Product: 
IMU-131 
IMU.ACS.001 
Protocol Identifier: 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
g 
h 
k 
Chemotherapy for all patients: cisplatin, IV (80 mg/m2 on Day 14, then every 21 days) and either 5-FU, 4000 mg/m2 CIV (administered as 1000 mg/m2/day as 
continuous infusion for 96 hours on Days 14 to 17, then every 21 days) or capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice 
daily morning and evening for a total of2000 mg/m2/day on Days 14 to 27, then every 21 days). Body weight to be measured and body surface area to be calculated 
based on weight and baseline height at the start of each 21 day chemotherapy cycle. Chemotherapy continues until ceased by the investigator as clinically indicated for 
the care of the patient. To document compliance while away from the clinic, patients will record capecitabine treatment in a patient diary. 
Photographs will be taken for vaccination site evaluation if there are visible local injection site reactions. 
First booster dose ofIMU-131 for long-term maintenance. Booster doses continue every 12 weeks. 
Radiographic assessment to occur within the screening period, then at Days 56, 98 and each L TM visit. Radiographic assessment continues until disease progression 
according to RECIST 1.1 response criteria or if unacceptable toxicity occurs. 
Patients who complete Day 56 will continue in long term maintenance. Treatment and procedures for long term maintenance are according to Table 2: Schedule of 
Activities Long Term Maintenance. 
If not ceased prior to start oflong term maintenance then chemotherapy continues until ceased by the investigator as clinically indicated for the care of the patient. 
Cardiac assessment includes 12-lead ECG and evaluation ofL VEF by echocardiography or MUGA scan. 
No tumor biopsy is required if a previous pathology result or archival tissue is available confirming HER2/neu expression consistent with Inclusion Criteria #6. 
IMUGENE LIMITED 
Page 42 of 121 
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Investigational Product: 
Protocol Identifier: 
Protocol Version: 
IMU-131 
IMU.ACS.001 
Protocol Global Amendment #5, 27 September 2023 
Table 3: 
Schedule of Activities Phase 2 and Phase 2 Extension 
Week2K 
Week3 
Week5K 
Week6 
Week9 
Screen 
Baseline 
(+/- 3d) 
(+/- 3d) 
(+/- 3d) 
(+/- 3d) 
(+/- 7d) 
Study Days 
-2ld to-Id 
0 
14 
21 
35 
42 
63 
Survival/anti-cancer treatment 
IMU-13 I Vaccination 
X 
X 
X 
Chemotherapy0 .F 
X 
X 
X 
X 
Informed Consent 
X 
Demographics and prior medications 
X 
Medical History 
X 
Cancer History 
X 
Physical ExamN 
X 
X 
X 
X 
X 
Weight and vital signs (temp, BP, 
X 
X 
X 
X 
X 
X 
X 
pulse)1-
Height 
X 
ECOG performance status 
X 
X 
Radiographic Assessment" 
X 
X 
Cardiac AssessmentH 
X 
IMUGENE LIMITED 
CONFIDENTIAL 
Post-treat 
WeekllK 
Weekll 
Week15 
Week18 
Week2oK 
EoTVisit0 
ment 
FUVisitQ.R 
(+/- 7d) 
(+/- 7d) 
(+/- 7d) 
(+/- 7d) 
(+/- 7d) 
(+/- 7d) 
(+/- 7d) 
84repeat 
126repeat 
140repeat 
At least28 
Every42 
77 
every 84 days 
105 
every 84 dayi 
every 63 days (+/- 7)Days 
days after 
(+/- 7d) 
(+/- 7d) 
(+/- 7d) 
after last dose 
EoT 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
XG 
X 
X 
Page 43 of 121 


Footnotes for Schedule of Activities – Phase 2 and Phase 2 Extension 
Investigational Product: 
Protocol Identifier: 
Protocol Version: 
Study Days 
Tumor biopsy1 
Urine Pregnancy Test' 
HIV, HepatitisM 
Hematology, ChemistryM 
Exploratory endpoint labs" 
Immunology - humoralc 
Immunology - cellular 
Concomitant Medications 
Concomitant Procedures 
Adverse Events 
IMU-131 
IMU.ACS.001 
Protocol Global Amendment #5, 27 September 2023 
Week2K 
Week3 
Week5K 
Week6 
Week9 
Screen 
Baseline 
(+/- 3d) 
(+/- 3d) 
(+/- 3d) 
(+/- 3d) 
(+/- 7d) 
-2ld to-Id 
0 
14 
21 
35 
42 
63 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
x 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Post-treat 
WeekllK 
Weekll 
Week15 
Week18 
Week201' 
EoTVisit0 
ment 
FUVisitQ.R 
(+/- 7d) 
(+/- 7d) 
(+/- 7d) 
(+/- 7d) 
(+/- 7d) 
(+/- 7d) 
(+/- 7d) 
84repeat 
126repeat 
140repeat 
At least28 
Every42 
77 
every 84 days 
105 
every 84 dayi 
every 63 days (+/- 7)Days 
days after 
(+/- 7d) 
(+/- 7d) 
(+/- 7d) 
after last dose 
EoT 
)( 
)( 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
A 
Negative urine pregnancy test required for women of childbearing potential at screening and prior to each vaccination. If positive urine test vaccination may be 
delayed until negative BHCG blood test. 
B 
A 1 x 10 mL whole blood sample to assess vaccine-specific cytokine levels and in-vitro inhibition of tumor cell growth will be obtained from each patient at 
Days 0, 84 then every 84 days and at EoT visit. 
IMUGENE LIMITED 
Page 44 of 121 
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Investigational Product: 
Protocol Identifier: 
Protocol Version: 
IMU-131 
IMU.ACS.001 
Protocol Global Amendment #5, 27 September 2023 
C 
1 x 10 mL (i.e. 1 tube) whole blood sample for humoral immunity at Baseline, Days 21, 42, 63, 84, 126 then every 42 days and EoT visit and 40 mL blood 
sample at Screening (Phase 2 Extension only), Baseline, Days 84 then every 84 days and EoT visit for cellular immunity. To be taken prior to vaccination at 
Baseline visit. 
D 
Chemotherapy will be administered as a concomitant therapy to all patients as a 21-day regimen consisting of: cisplatin by intravenous administration at 80 
mg/m2 on the first day of each cycle and either 5-FU, 4000 mg/m2 CIV (administered as 1000 mg/m2/day as continuous infusion for 96 hours on days 1 to 4 of 
each cycle) or capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total of2000 mg/m2/day 
on days 1 to 14 of each cycle), or capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice daily morning and evening for a total 
of 2000 mg/m2/day on days 1 to 14 of each cycle) and oxaliplatin, by intravenous administration at 130 mg/m2 on Day 1 of each cycle. Body weight to be 
measured and body surface area to be calculated based on weight and baseline height at the start of each 21-day chemotherapy cycle. Chemotherapy continues 
until ceased by the investigator as clinically indicated for the care of the patient. To document compliance while away from the clinic, patients will record 
capecitabine treatment in a patient diary. 
E 
Radiographic assessment to occur within 14 days prior to Baseline Visit, then at Days 42, 84, 126 every 42 days thereafter. Radiographic assessment continues 
until disease progression according to RECIST 1.1 response criteria, withdrawal or end of trial. 
F 
Chemotherapy continues for up to 6 cycles until disease progression or until ceased by the investigator as clinically indicated for the care of the patient, whichever 
occurs first. 
G 
Radiographic assessment according to RECIST 1.1 response criteria at post-treatment follow-up visit only for patients who have ended study treatment prior to 
disease progression. 
H 
Cardiac assessment will be based on assessment of medical history, physical examination, 12-lead ECG results and evaluation L VEF by echocardiography or 
MUGA scan at Screening, Days 84 then every 84 days and at EoT visit. 
No tumor biopsy is required if a previous pathology result or archival tissue is available confirming HER2/neu expression consistent with Inclusion Criteria #6. 
J 
Optional Day 84 and post-progression tumor biopsy (which may be provided at any time post progression). 
K 
Visit only for 'IMU-131 plus chemotherapy' group. 
L 
Record temperature 30min (+/- 10mins) after each IMU-131 vaccination. 
M 
Local laboratory testing. Safety lab samples can be drawn up to 72 hours before any on-study clinic visit. 
N 
A targeted, symptom directed physical examination may be performed at visits occurring after the Baseline Visit. 
0 
When progressive disease or withdrawal from study has been confirmed, EoT visit will be conducted at least 28 Days(+/- 7) after last dose of study medication. AEs 
to be checked at least 28 days after last study treatment per Section 9.2: Reporting Period. 
P 
Phase 2 Extension only: Screening 40 mL cellular immunity blood sample after enrolment eligibility including HER2 over-expression is confirmed. 
Q 
Phase 2 only: Phase 2 Extension patients will no longer complete Post Treatment Follow Up Visits 
IMUGENE LIMITED 
Page 45 of 121 
CONFIDENTIAL 


Investigational Product: 
Protocol Identifier: 
Protocol Version: 
IMU-131 
IMU.ACS.001 
Protocol Global Amendment #5, 27 September 2023 
R 
R End of trial is defined as 28 days post the last patient completing the end of treatment visit. 
IMUGENE LIMITED 
CONFIDENTIAL 
Page 46 of 121 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
IMUGENE LIMITED 
Page 47 of 121 
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1.
INTRODUCTION
1.1. 
Indication  
IMU-131 is a single peptide composed of 3 individual B-cell epitope peptide sequences 
selected from the HER2/neu structure which induces the patient’s own B-cells to produce 
endogenous anti-HER2/neu antibodies. IMU-131 is being developed for the treatment of 
patients with HER2/neu overexpressing metastatic or advanced adenocarcinoma of the 
stomach or gastroesophageal junction (referred to as advanced cancer of the stomach or 
ACS). 
1.2. 
Background and Rationale 
Almost one million new cases of gastric cancer were estimated to have occurred in 2016, 
making it the fifth most common malignancy in the world, and gastric cancer is the third 
leading cause of cancer death worldwide (Siegel et al., 2016), and is the second most 
common cause in many Asian countries, such as China, Japan, and Korea. 
Gastric cancer is considered an unmet medical need. Advanced cancer of the stomach 
(ACS) differs in its global epidemiology and patient predisposition. Whereas the incidence 
of ACS is lower in countries of the Western world, it is prevalent in countries of the Eastern 
hemisphere. Asia covers a large geographical area: it has more than 40 countries and diverse 
ethnic groups. Socioeconomic conditions, political status, and health-care systems vary 
widely between different Asian countries. Data for individual countries show that gastric 
cancer is the most common cancer in Japan and the second most common in China and 
Korea; in Singapore, Taiwan, and Philippines, gastric cancer is one of the five most 
common types of cancer. Its prevalence is high in countries with limited financial resources 
and in socially underprivileged individuals. This situation leads to the problem of delivery 
of optimal treatment options, particularly in countries with limited financial resources and 
particularly to socially underprivileged individuals. 
ACS occurs predominantly in a primarily inoperable state with metastatic spread to distant 
lymph nodes or to inner organs and – if operable – tends to recur frequently. The American 
Cancer Society reports that patients with Stage IIIc and IV gastric cancer can expect 5-year 
survival rates of only 9% and 4%, respectively (American Cancer Society, 2014). For initial 
systemic treatment for metastatic and locally advanced cancer where local treatment is not 
indicated, 2-drug combinations are preferred over 3-drug combinations due to its lower 
luoropyrimidine (e.g., 5-fluorouracil [5-FU], intravenous [IV] or 
capecitabine, oral) and platinum-based (e.g., cisplatin, IV or oxaliplatin, IV) chemotherapy 
 are recommended in the current US National Comprehensive Cancer Network® Clinical 
Practice Guidelines in Oncology - Gastric Cancer (NCCN, 2017; NCCN 2018). 
The transmembrane tyrosine kinase receptor HER2/neu (Human Epidermal Growth Factor 
Receptor 2) is also known as Neu, Erb-2, CD340, or p185 but is most commonly referred 
to as HER2/neu (Coussens et al, 1985). It is a member of the epidermal growth factor 
receptor (EGFR/ErbB) family. Amplification or overexpression of this receptor has been 
shown to play an important role in pathogenesis and progression of aggressive subsets of 
several types of cancer including ACS, breast cancer, ovarian cancer, uterine cancer (Santin 
et al, 2008; Tan and Yu, 2007), endometrial cancer, and others. It has been found to be 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
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Page 48 of 121 
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overexpressed in 15% to 25% of patients with gastric cancer (Hofmann et al, 2008; Park
et al, 2006; Yano et al, 2006; Zhang et al, 2009) where it is associated with a worse 
prognosis, more aggressive disease, and poorer survival. In tumors where HER2/neu is 
overexpressed, signaling through this receptor proceeds through the MAPKinase - 
PI3K/Akt - Phospholipase C - Protein Kinase C - STAT cascade promoting cell 
proliferation and opposing apoptosis (Roy and Perez, 2009). Where it is overexpressed, 
HER2/neu is typically the primary driver of proliferation for the malignant cells. 
The Phase 3 Trastuzumab for Gastric Cancer (ToGA) trial compared 5-FU (or capecitabine)
+ cisplatin ± trastuzumab in 594 patients with HER2/neu overexpressing gastric or GEJ
adenocarcinoma. Median overall survival (OS) was significantly improved with
trastuzumab compared to chemotherapy alone: 13.5 vs 11.1 months (p=0.0048). The
overall response rates were 47.3% in the trastuzumab + chemotherapy arm vs 34.5% in the
chemotherapy alone arm (p=0.0017). Based on these data, the combination of trastuzumab
plus 5-FU and cisplatin chemotherapy has become registered as the standard therapeutic
option in combination with chemotherapy in first line setting in some countries.
Trastuzumab is costly, however, and has been associated with a serious decline in heart
function for some patients. Other potentially serious side effects include infusion reactions,
pulmonary edema, and respiratory distress. A pharmacoeconomic analysis of trastuzumab
in gastric cancer conducted by NICE in 2010 concluded that it was not cost effective (NICE,
2010) and a pharmacoeconomic analysis of the ToGA data concluded that trastuzumab
treatment may only be cost effective for a subgroup of gastric cancer patients defined
post hoc who were immunohistochemistry (IHC) 3+ for HER2/neu at baseline. Using
trastuzumab to treat all HER2-positive populations is not likely to be cost effective
(Shiroiwa et al, 2011).
Since trastuzumab may not be available or affordable in certain parts of the world including 
even parts of Western Europe and might be associated with adverse effects for certain 
patients, there is a need for alternative treatment options. One alternative approach to 
HER2/neu inhibition may be the induction of endogenous anti-HER2/neu antibodies by a 
patient’s own B-cells after treatment with a HER2/neu-directed vaccine, such as IMU-131. 
Active specific immunization against HER2/neu amino acid sequences may result in 
persisting antibody formation in humans. This approach in a predecessor formulation to 
IMU-131 (PEV6C) was highly effective in reducing tumor growth in animal models of 
HER2/neu overexpressing tumors and has undergone Phase 1a testing that demonstrated 
the safety and immunogenicity of the vaccine (Wiedermann et al, 2010). 
This study has a 2-part design. The Part 1 (Phase1b) component is aimed at determining 
the safety of IMU-131 and an optimal immunological dose of IMU-131, to carry into the 
Part 2 (Phase 2) dose expansion component of the study. Part 2 will immediately follow 
Part 1 and is designed to evaluate efficacy and to further characterize the safety and clinical 
activity of IMU-131 in combination with chemotherapy in HER2/neu overexpressing 
advanced gastric or GEJ adenocarcinoma. 
1.3. 
IMU-131 (HER2/neu Peptide Vaccine) 
The investigational medicinal product IMU-131 is a sterile solution in PBS buffer of the 
Her-2/neu antigen P467 linked to non-toxic diphtheria CRM197 protein (P467-CRM197) 
. The peptide antigen component 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
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Page 49 of 121 
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of IMU-131 is a single peptide design composed of 3 individual B-cell epitope peptide 
sequences selected from the HER2/neu structure and are the identical peptides being 
investigated in the predecessor formulation PEV6C (Wiedermann et al, 2010). Polyclonal 
antibodies generated against IMU-131 peptides bind three separate regions of the HER2 
receptor in domains III and IV thereby inhibiting intracellular signaling and inducing 
antibody dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity 
(CDC). HER2/neu, gene product of erbB2/neu protooncogene, is a 185 kDa protein that 
belongs to the epidermal growth factor receptor family. It consists of a cysteine rich 
extracellular domain (ECD) with several glycosylation sites, a hydrophobic transmembrane 
domain, and an intracellular conserved tyrosine kinase domain. HER2/neu is weakly 
detectable in epithelial cells of normal tissues but is overexpressed in 15 - 25% of several 
cancers including primary breast, gastric and prostate cancer, and has been linked with a 
poor prognosis, more aggressive disease progression and high risk of cancer relapse. The 
overexpression seems to be stable and homogenous in primary tumors as well as their 
metastases. These findings suggest HER-2/neu may be an attractive target of cancer 
immunotherapy. In vitro and in vivo animal experiments with an earlier formulation of 
IMU-131, PEV6C, have corroborated this approach and have shown the ability to generate 
an effective antibody response by human B-cells (Wagner et al, 2007).† These antibodies 
were able to induce ADCC and CDC and to inhibit the proliferation of HER2/neu 
overexpressing tumor cells in vitro. PEV6C was also able to effectively inhibit the 
emergence of HER2/neu overexpressing breast tumors in a transgenic mouse model (Roy 
and Perez, 2009). 
IMU-131 is a HER2/neu antigen peptide – adjuvant emulsion (P467-CRM197 – Montanide 
emulsion) which is injected intramuscularly (IM) into the patient to stimulate innate 
immunity in response and is processed by antigen presenting cells. The immune system 
then generates specific adaptive immunity to the HER2/neu antigen peptides. This 
ultimately leads to the development of B-cells that secrete endogenous HER2/neu-specific 
antibodies that block binding HER2 signaling. Blocking HER2 signaling inhibits 
proliferation and enables apoptosis in HER2/neu overexpressing tumor cells. Antibody 
binding to these cells can also signal for additional immunologic clearance through ADCC 
and CDC. Immunization with this multi-epitope vaccine performed in a c-neu transgenic 
mouse model demonstrated that the vaccine led to delayed onset of tumor growth and 
reduced tumor progression in vivo (Wagner et al, 2007), providing the rationale to move 
into human clinical testing. 
Several strategies of combining cancer vaccines with chemotherapy have been tested. 
Various chemotherapy regimen have been evaluated in combination with immunotherapies, 
e.g. vaccines, with regards to the beneficial effect chemotherapy might have in enhancing
the immune response triggered by vaccines. These studies have revealed that immune- 
stimulatory cancer vaccines can be safely used in combination with immunosuppressive
chemotherapies to condition the immune system and to create an environment where cancer
vaccines have a better chance of success. Among the chemotherapies tested to enhance
immune responses from vaccines, the underlying mechanism of supporting the immune
response of vaccines are favorably described for 5-FU- and Cisplatin-based regimen and
provide a rationale for the combination of both chemotherapies with an immune- 
stimulatory vaccine (Weir et al, 2011). A study of the effect of 5-FU chemotherapy on
patients diagnosed with lung cancer reported that immunization with an anti-idiotype
antibody, designated CeaVac (a monoclonal antibody with an internal image of CEA), had


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
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Page 50 of 121 
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no qualitative or quantitative effect on the anti-CEA immune response (Foon et al, 1999). 
Gastric cancer patients have been successfully immunized with G17DT immunogen 
resulting in anti-gastrin titers while receiving simultaneous cisplatin and 5-FU 
chemotherapy (Alanji et al, 2006). Matsushita et al (2013) in a Phase 1 trial treated patients 
with advanced gastric cancer using a vaccine containing a mixture of synthetic peptides 
and oral tegafur/uracil leucovorin. Among the 10 treated patients the responses were 1 
Partial Response and 7 Stable Disease. 
In the phase 1 study of IMU-131 predecessor, PEV6C, eight of the 10 patients exhibited an 
increase in HER2/neu-specific antibody titers directed against vaccine peptides as well as 
native HER2/neu protein. A marked increase in cellular immune responses was observed 
in the majority of vaccinated patients. In addition, the number of CD4+CD25+Foxp3+ T- 
regulatory cells was markedly reduced following vaccination, suggesting the vaccine was 
effective in overcoming immunological tolerance to HER2/neu. These data support that the 
3 peptide sequences contained in IMU-131 are effective in generating antibodies against 
HER2/neu as well as inducing additional immunologic changes that increase the activity of 
cellular immunity and reduce immunologic tolerance to HER2/neu expressing cells. 
The Phase 1b study has been designed with 2 immunizations prior to initiating 
chemotherapy so that there is a maximum chance that vaccine-specific B and T cells can 
be primed, antibody production initiated, and memory cells induced. This will provide the 
optimal environment for patients to generate high anti-HER2 antibody titres and for the 
appropriate recommended phase 2 dose to be accurately determined. 
A common side effect of chemotherapy, including cisplatin and 5-FU treatment of 
advanced or metastatic gastric cancer is myelosuppression (Florea and Büsselberg, 2011; 
Kim et al, 1993; Kim et al, 2000; Kim, 2005; Leong, 2005; Ozkan et al, 2005) which may 
lead to a reduction in available B cell lymphocytes and the potential antibody response to 
IMU-131. Moreover, memory B cells within the lymph nodes and induced plasma cells 
will be less affected than if vaccination is started post chemotherapy because patients 
undergoing chemotherapy do not lose their vaccine memory to vaccines like diphtheria or 
tetanus when these vaccinations occur before the start of chemotherapy (Haining et al, 
2005; Laws et al, 2005). From vaccinology point of view it is therefore highly 
recommended to vaccinate before onset of chemotherapy (Giese, 2016; Wiedermann et al, 
2016). 
Generating high antibody titers are critical when using vaccines to induce antibodies to 
immuno-oncology targets. For example, the anti-EGF B-cell vaccine ‘CIMAvax’ for non- 
small cell lung cancer (NSCLC) demonstrates that patients’ survival rate increases with 
amount of antibody production with a strong correlation between survival rates and level 
of antibody titres with Poor Antibody Responders (PAG; maximal antibody titer < 1:4000) 
surviving a mean of 5.5 months vs Good Antibody Responders (GAR; maximal antibody 
titer > 1:4000) surviving a mean of 10.5 months and super Good Antibody Responders 
(sGAR, maximal antibody titer >1:64000) surviving a mean of 25.6 months (Gonzalez 
et al, 2003; Rodriguez et al, 2010; Neninger et al, 2009). 
A study of the anti-EGF B-cell vaccine ‘CIMAvax’ for NSCLC demonstrated stronger 
antibody production and longer survival rates in patients when CIMAvax was initiated prior 
to first–line chemotherapy (Neninger et al, 2009). The results of this study show antibody 


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
Protocol Version: 
Protocol Global Amendment #5, 27 September 2023 
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Page 51 of 121 
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titers were significantly higher compared to when chemotherapy preceded vaccination. In 
this study the geometric mean of maximal antibody titers was 1:76,109, compared to 1:3160 
when chemotherapy preceded vaccination with 95% of the patients classified as Good 
Antibody Responders (GAR, maximal antibody titer > 1:4000) compared to 51% reaching 
this threshold when chemotherapy preceded vaccination. Moreover 55% patients 
vaccinated prior to chemotherapy were classified as super Good Antibody Responders 
(sGAR, maximal antibody titer > 1:64000) whereas only 2.8% of patients were classified 
as sGAR when vaccinated after chemotherapy. Furthermore, it is important to note that the 
increase in immunogenicity produced with pre-chemotherapy vaccinations of CIMAvax 
was associated with an increase in overall survival but was not associated with increased 
toxicity (Neninger et al, 2009). 
Within the Phase 1b study as of the data cut-off of 07 November 2018, IMU-131 has been 
administered to 14 patients with advanced gastric or GEJ cancer at dose of 10 to 50 µg 
peptide P467 antigen equivalent (3 doses on Days 0, 14, and 35) with 11 completing the 
study through Day 56. No dose-limiting toxicities were reported for any patients. No 
injection site reactions were reported at 2 days post-dose for any patients; however, Grade 
1 AEs of redness and itch on right upper arm in the same subject with onset 3 days after 
third injection of 50 µg dose and resolution without intervention the next day were assessed 
by the Investigator as possibly related to IMU-131. The Investigators assessed only 2 AEs 
as related to IMU-131 (Grade 2 hypoalbuminemia and Grade 3 hyponatremia in the same 
subject) and 4 AEs as possibly related to IMU-131 (Grade 2 weight loss and Grade 1 
anorexia in the same subject, Grade 1 redness and itch in the same subject). No serious 
adverse reactions have been reported. Decreases in LVEF, which were substantial in 3 
(27%) patients, were transient and had no clinical correlation. 
In the Phase 1b study IMU-131 elicited anti-P467 and anti-HER-2 antibodies that increased 
both with increased doses and after subsequent doses. Of the 10 patients who have 
completed the study through Day 56 and had measurable disease at Baseline, 5 had a partial 
response, and 3 others had a measurable decrease in tumor size. 
The preliminary immunology and clinical response data from Phase 1b are promising. 
Safety data to date indicate that IMU-131 is well tolerated with no significant local or 
systemic reactions, and no need for pretreatment or for modification to the dose or treatment 
schedule due to safety. The safety and immunological data from Phase 1b supported a dose 
of 50 µg peptide P467 antigen equivalent conjugated to CRM197 in a Montanide emulsion 
(IMU-131) as a 0.5 mL injection on Days, 0, 14, 35 followed by a booster 42 days later and 
subsequent boosters every 63 days (Wiedermann et. al., 2021). 
The Phase 2 study has been designed with the treatment group (IMU-131 plus 
chemotherapy) receiving immunization and chemotherapy starting on the same day because 
1) analysis of immunological responses in patients in Phase 1b did not show a detrimental
effect of chemotherapy on the development of either anti-P467 or anti-HER-2 antibodies
at any timepoint associated with chemotherapy treatment and 2) having the same
chemotherapy schedule in the treatment and control groups in Phase 2 strengthens the
statistical validity of the time-based secondary efficacy endpoint analysis.
The rationale to increase the dose of IMU-131 is justified by existing clinical data with no 
dose limiting toxicity duri


Investigational Product: 
IMU-131 
Protocol Identifier: 
IMU.ACS.001 
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phase 2 dose based on Her2/neu antibody development and response compared to the lower 
dose levels studied. In addition, safety data from the ongoing Phase 2 study supports dose 
escalation above 50
-131 because no IMU-131 related safety signals, dose limiting 
toxicities, or SUSARs have been detected. The Phase 2 dose escalation study will therefore 
explore whether an increased dose will produce earlier and stronger development of 
Her2/neu antibodies, which may potentially support the use of IMU-131 in patients who 
progress after developing resistance to trastuzumab (Rexer and Arteaga, 2012). The Phase 
2 extension study will evaluate two dose levels for safety, efficacy, and immunogenicity. 
The safe administration of IMU-131 at higher doses will set the stage for a further Phase 2 
extension study in second-line treatment of metastatic/advanced gastric and GEJ cancer in 
patients that have progressed under trastuzumab. Additional support for introducing higher 
doses of IMU-131 comes from two patients participating in the ongoing Phase 2 study. 
Two patients (SB03-202, SB03-204) erroneously received an initial 3 and 2 consecutive 
doses of 100ug IMU-131, respectively. These patients showed stronger and earlier 
progression free survival of 42 and 36 weeks, respectively, with no significant adverse 
events indicating that patients may benefit from the higher doses of IMU-131. 
It is hypothesized that administration of IMU-131 in combination with chemotherapy will 
prolong survival and may delay tumor progression and/or reduce tumor burden in patients 
with HER2/neu overexpressing gastric or GEJ adenocarcinoma. It is anticipated that 
due to the selective targeting of multiple epitopes on the HER2 receptor (including the 
epitope targeted by trastuzumab and the functionally important HER2 dimerization region) 
and the expected immune response, that IMU-131 could convey an efficacy advantage over 
trastuzumab as well as a potential safety, and/or a more favorable side effect profile, 
particularly over a longer period of dosing, due to the stimulation of the patient’s own 
immune system. Lastly, IMU-131 may have a cost advantage over semi-synthetic 
antibodies, which may confer cost and therefore access advantages over trastuzumab. 
†The original formulation of IMU-131 (or PEV6C) was composed of the three individual B-cell epitope 
peptides whereas the new, current formulation combines all three in a specific order resulting in a single 
fusion peptide of 49 amino acids in length. This new formulation of IMU-131 has shown improved stability 
as well as equal and improved immunogenicity compared to the original formulation. 
1.4. 
Risk/Benefit analysis for IMU-131 (HER2/neu Peptide Vaccine) 
It is anticipated that the information gained from this study will contribute to the 
development of a safe and effective anti-HER2/neu peptide vaccine. It is unknown whether 
patients will benefit from participation in this study. The investigational product-related 
risks to patients in this study are associated with the general risk of vaccination, however 
IMU-131 in the Phase 1b study revealed no systemic toxicities with only mild local 
injection site reactions. The volume of blood drawn over the study period is not expected 
to compromise patients. 
The general risks to patients will arise from their common chemotherapy. Serious and 
potentially fatal specific and general risks are associated with cisplatin and either 5-FU or 
capecitabine combination chemotherapy, or oxaliplatin and capecitabine combination 
chemotherapy, that will be administered to patients on this trial. These treatments are 
standard care for this disease (NCCN, 2018) and are given in a standard fashion that is 


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familiar to all investigators, but all patients are likely to experience some chemotherapy- 
associated adverse events (AEs). 
Vaccination-specific potential risks include the following: 
Local reactions: An inflammatory reaction as manifested by redness, swelling, and/or 
tenderness may occur at the site of vaccine injection. Local reactions are expected to resolve 
within days to weeks without medical intervention and sequelae. 
Systemic reactions: May include flu-like symptoms with low-grade fever, chills, and 
malaise. Experience to date with other peptide vaccines suggests that if such reactions 
occur, they resolve in days to weeks without therapy or limitation of daily activity. Serum 
sickness reactions due to deposition of antigen-antibody complexes or idiosyncratic 
immune responses not dependent on immune complexes could develop, resulting in 
damage to organs such as the liver or kidney. Such immune-mediated reactions have not 
been reported to date for HER2/neu peptide vaccines. Temporary ascending paralysis, the 
Guillain-Barré syndrome, may occur with any vaccine, although it is very rare. 
Allergic reactions and anaphylaxis: Allergic and anaphylactic reactions are also possible. 
No such reactions have been observed to date. 
The design of the Phase 1b study enables close medical monitoring of patients. Physical 
monitoring of patients occurs after each vaccination and 2 days post vaccination during 
each dose period. Cohort Review Committee (CRC) meetings and site teleconferences 
between the medical monitor and investigational site staff will occur regularly during the 
study. 
Similarly, the design of the Phase 2 and Phase 2 Extension studies support appropriate 
medical monitoring of patients. Physical monitoring of patients occurs after each 
vaccination and at regular intervals during each study. Independent Data Monitoring 
Committee (IDMC) meetings during Phase 2 and CRC meetings during Phase 2 dose 
escalation, as well as site teleconferences between the medical monitor, Sponsor 
representatives and investigational site staff will occur regularly during the study. 
Complete information for IMU-131 may be found in the Single Reference Safety 
Document, which for this study is the Investigator Brochure. 
2.
STUDY OBJECTIVES AND ENDPOINTS
2.1. 
Objectives 
This phase1b/2 protocol is made up of 2 components. 
Phase 1b aims to determine the safety and tolerability of IMU-131 and identify the 
Recommended Phase 2 Dose (RP2D) of IMU-131 in combination with chemotherapy in 
HER2/neu overexpressing ACS to carry into the Phase 2 dose expansion study. The Phase 
2 component will be submitted as an amendment and will be initiated following completion 
of Phase 1b. Phase 2 will be designed to further characterize the safety and to explore 
clinical activity of IMU-131 in combination with chemotherapy in HER2/neu 
overexpressing ACS. 


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Phase 2 is an open-label, randomized, multicenter study designed to assess the clinical 
activity, immunogenicity, safety and tolerability of IMU-131. The length of Phase 2 will 
be approximately 30 months: 22 months’ recruitment and an estimated 8 months’ follow-
up from completion of recruitment to realization of the required number of deaths. 
It is anticipated that an additional 3 months will be required to complete the analyses 
following realization of the last required death. 
Phase 2 Extension 
Dose escalation during Phase 2 is an open-label, multicenter, single arm dose escalation 
study with the same inclusion/exclusion criteria as Phase 2 and the same schedule of 
assessments as Phase 2 IMU-131+chemotherapy arm. The safety of each dose will be 
assessed by CRC after at least 3 patients have 3 doses of IMU-131 and one cycle of 
chemotherapy and have completed the 35 day DLT window. Two dose cohorts, consisting 
-131, will further characterize the safety,
immunogenicity, and clinical activity of IMU-131 in combination with chemotherapy. 
Phase 1b objectives: 
To evaluate the safety and tolerability of IMU-131 
administered 
intramuscularly (IM) and initiated 14 days (+/- 1 day) prior to cisplatin, 
intravenous (IV) and either 5-FU, IV or capecitabine, oral chemotherapy in 
patients with HER2/neu overexpressing ACS; 
To identify the Recommended Phase 2 Dose of IMU-131, administered IM and 
initiated 14 days (+/- 1 day) prior to chemotherapy in patients with HER2/neu 
overexpressing ACS for evaluation in Phase 2. 
Phase 1b exploratory objectives: 
Humoral and tumoral immunogenicity data will be used to further explore the 
mechanism of action for anti-tumor effects of IMU-131; 
 
Radiographic data will be used for an exploratory determination of Response Rate. 
Phase 2 primary objective: 
To evaluate the clinical efficacy of IMU-131 plus chemotherapy compared to 
chemotherapy alone based on overall survival (OS). 
Phase 2 secondary objectives: 
To evaluate other efficacy measures of IMU-131 plus chemotherapy compared to 
chemotherapy alone including progression-free survival (PFS), time to 
progression (TTP), disease control rate (DCR), objective response rate (ORR), 
duration of objective response (DOR) and change in tumor size (CTS) according 
to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1) for the 
progression evaluation of radiographic data. 
To evaluate the safety profile of IMU-131 plus chemotherapy compared to 
chemotherapy alone. 


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Phase 2 exploratory objectives: 
To evaluate humoral and cellular immunogenicity data of IMU-131 plus 
chemotherapy compared to chemotherapy alone including P467-specific 
antibodies (IgG), Her-2-specific antibodies (IgG), vaccine-specific cytokine 
levels and regulatory and effector T and B cells. 
To evaluate the arm-specific associations between clinical outcome, intra-tumor T 
cells, regulatory and effector T and B cells, and serum and biochemical markers 
of tumor progression 
To evaluate arm-specific associations between clinical outcome and HER2 and 
PD- L1 expression in tumor tissue. 
To evaluate inhibition of in-vitro tumor cell growth and intra-cellular signaling 
processes by Her-2-specific antibodies (IgG). 
Phase 2 Dose Escalation Primary Objective: 
-131 in
combination with chemotherapy. 
Phase 2 Dose Escalation Secondary Objectives: 
To evaluate efficacy of IMU-131 plus chemotherapy including OS, PFS, TTP, 
ORR, DOR, DCR, and CTS according to Response Evaluation Criteria In Solid 
Tumors version 1.1 (RECIST 1.1) for the progression evaluation of radiographic 
data. 
Phase 2 Dose Escalation Exploratory Objectives: 
To evaluate humoral and cellular immunogenicity data of IMU-131 plus 
chemotherapy compared to chemotherapy alone including P467-specific 
antibodies (IgG), Her-2-specific antibodies (IgG), vaccine-specific cytokine 
levels and regulatory and effector T and B cells. 
To evaluate the associations between clinical outcome, intra-tumor T cells, 
regulatory and effector T and B cells, and serum and biochemical markers of 
tumor progression. 
To evaluate associations between clinical outcome and HER2 and PD- L1 
expression in tumor tissue. 
To evaluate inhibition of in-vitro tumor cell growth and intra-cellular signaling 
processes by Her-2-specific antibodies (IgG). 
2.2. 
Endpoints 
In Phase 1b, toxicity data for each cohort will be reviewed prior to each dose escalation 
by a Cohort Review Committee (CRC). The CRC consists of both Investigator site and 
Sponsor representatives. Investigator site representatives will include the Principal 
Investigator and any ancillary staff identified by the Principal Investigator. The Sponsor 
representatives will include the medical monitor and clinical trial manager and other 
designee. Each CRC meeting will be held after each dose cohort is complete and prior to 
initiation of the next dose cohort. The CRC will review the complete, pre-defined safety 


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and immunogenicity dataset from each dose cohort and will determine, with advice from 
the Principal Oncologist and Clinical Immunologist, the appropriate dose limiting toxicity 
(DLT) rule (see Sections 10.1.1 and 10.1.2 for details) and whether the study will proceed 
to the next dose cohort. All patients in a dose cohort must have completed chemotherapy 
cycle 1 (35 days of the study, including 3 doses of IMU-131) prior to the CRC meeting 
and opening of the next higher dose cohort for enrollment. 
Phase 1b endpoints: 
The safety and tolerability of IMU-131 will be evaluated by adverse events (AEs) 
and laboratory measurements. AEs and laboratory abnormalities will be graded 
by Common Terminology Criteria for Adverse Events (CTCAE) v4.03; 
The recommended phase 2 dose will be evaluated by safety/tolerability and 
immunogenicity data for IMU-131 (P467-specific antibodies (IgG) and Her-2- 
specific antibodies (IgG) titers). 
Phase 1b exploratory endpoints: 
Humoral and cellular immunogenicity data will include P467-specific antibodies 
(IgG) and Her-2- specific antibodies (IgG) in serum samples and vaccine-specific 
cytokine levels as well as analysis of regulatory and effector T and B cells taken 
across study visits. As prediction markers of tumor progression initial evaluation 
(prior first vaccination) of intra-tumor T cells and regulatory cells in tumor 
biopsies will be performed, when these tests are available at the hospital pathology 
laboratory. 
Radiographic data will be analyzed descriptively to explore Response Rate and 
provide information for sample size calculation for the Phase 2 study. 
Phase 2 primary efficacy endpoint: 
 
OS measured from randomization to death due to any cause.  
Phase 2 secondary efficacy endpoints: 
PFS measured from randomization to date of earliest progressive disease (PD) 
based on blinded central review according to RECIST 1.1 criteria, or to date of 
death from any cause. 
TTP measured from randomization to date of earliest PD based on blinded central 
review according to RECIST 1.1 criteria. 
DCR measured from randomization as the proportion of patients achieving a 
confirmed best overall response of complete response (CR), partial response 
(PR) or stable disease (SD) based on blinded central review according to RECIST 
1.1 criteria. 
ORR measured from randomization as the proportion of patients achieving a 
confirmed best overall response of CR or PR based on blinded central review 
according to RECIST 1.1 criteria. 
DOR measured from when earliest CR or PR is observed to PD or death due to 
any cause based on blinded central review according to RECIST 1.1 criteria. 


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Percentage CTS measured from randomization as the sum of diameters based on 
blinded central review according to RECIST 1.1 criteria. 
Phase 2 exploratory endpoints: 
Values and changes from randomization in humoral and cellular immunogenicity 
data including P467-specific antibodies (IgG), Her-2-specific antibodies (IgG), 
vaccine-specific cytokine levels and regulatory and effector T and B cells. 
Values and changes from randomization in serum prediction markers of tumor 
progression. 
Values and changes from randomization in Her-2-specific antibodies (IgG) 
inhibition of in-vitro tumor cell growth. 
Values and changes in intra-tumor T cells and biochemical markers from pre- and 
post- treatment tumor biopsies. 
Phase 2 Safety Endpoints: 
Incidence of treatment-emergent adverse events (TEAEs), Grade 3 / 4 / 5 TEAEs, 
serious adverse events (SAEs), and TEAEs leading to study treatment 
discontinuation. 
Incidence of treatment-emergent Grade 3 / 4 clinical laboratory abnormalities. 
Changes and shifts from randomization in clinical laboratory, vital signs, and 
electrocardiogram (ECG) parameters. 
Change from randomization in ECOG performance grade. 
Concomitant medication use. 
Treatment compliance. 
Phase 2 Dose Escalation Primary Endpoint: 
The safety and tolerability of IMU-131 will be evaluated by adverse events (AEs) 
and laboratory measurements. AEs and laboratory abnormalities will be graded 
by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 including: 
-
Incidence of treatment-emergent adverse events (TEAEs), Grade 3 / 4 / 5
TEAEs, serious adverse events (SAEs), and TEAEs leading to study
treatment discontinuation.
-
Incidence of treatment-emergent Grade 3 / 4 clinical laboratory
abnormalities.
-
Changes and shifts in clinical laboratory, vital signs, and electrocardiogram
(ECG) parameters.
Phase 2 Dose Escalation Secondary Endpoints: 
OS measured from enrollment to death due to any cause. 
PFS measured from enrollment to date of earliest progressive disease (PD) 
based on Investigator disease assessment according to RECIST 1.1 criteria, or to 
date of death from any cause. 


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TTP measured from enrollment to date of earliest PD based on Investigator 
disease assessment according to RECIST 1.1 criteria. 
ORR measured from enrollment as the proportion of patients achieving a 
confirmed best overall response of CR or PR based on Investigator disease 
assessment according to RECIST 1.1 criteria. 
DOR measured from enrollment to when earliest CR or PR is observed to PD or 
death due to any cause based on Investigator disease assessment according to 
RECIST 1.1 criteria. 
DCR measured from enrollment as the proportion of patients achieving a 
confirmed best overall response of complete response (CR), partial response (PR) 
or stable disease (SD) based on Investigator disease assessment according to 
RECIST 1.1 criteria. 
Percentage CTS measured from enrollment as the sum of diameters based on 
Investigator disease assessment according to RECIST 1.1 criteria. 
Phase 2 Dose Escalation Exploratory Endpoints: 
Values and changes from enrollment in humoral and cellular immunogenicity data 
including P467-specific antibodies (IgG), Her-2-specific antibodies (IgG), 
vaccine- specific cytokine levels and regulatory and effector T and B cells. 
Values and changes from enrollment in serum and biochemical markers of tumor 
progression. 
Values and changes from enrollment in Her-2-specific antibodies (IgG) 
inhibition of in-vitro tumor cell growth. 
Values and changes from enrollment in intra-tumor T cells and biochemical 
markers from pre- and post- treatment tumor biopsies. 
3.
STUDY DESIGN
This protocol for patients with HER2/neu overexpressing metastatic or advanced 
adenocarcinoma of the stomach or GEJ has a 2-part design. 
Part 1 consists of Phase 1b: Dose Escalation 
Phase 1b is an open-label, single arm, dose escalation study to evaluate safety, tolerability 
and immunogenicity and to assess the RP2D of IMU-131 initiated 14 days prior to the start 
of chemotherapy. The first dose cohort will be administered 3 doses of 10µg IMU-131, the 
second dose cohort will be administered 3 doses of 30µg IMU-131 and the third dose cohort 
will be administered 3 doses of 50µg IMU-131. All patients entering the Phase 1b study 
will receive IMU-131 and chemotherapy. RP2D is defined as the dose resulting in the best 
safety/tolerability and immunology results and will be determined after all dose cohorts 
have completed Day 56 of the study and an interim analysis of the Phase 1b data has been 
conducted by the CRC. 
Phase 1b follows a standard and well validated dose escalation methodology. Review of 
toxicity data will be conducted by the CRC as soon as each dose level cohort has completed 
chemotherapy cycle 1 (35 days of the study, including 3 doses of IMU-131) to ensure 


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ongoing scrutiny of the IMU-131 safety profile. Phase 1b dose escalation will involve 
3 dose levels of IMU-131 within a standard 3+3 scheme for determination of safety prior 
to dose escalation to next dose cohort. Within the 3+3 scheme if the CRC determines there 
is no dose-limiting toxicity (DLT) for any of the 3 patients in a dose cohort then only 
3 patients will enter this cohort before the next dose cohort is opened to recruitment. 
However if 1 of 3 patients in a cohort has a DLT event then an additional 3 patients will 
be enrolled at the existing dose level for further evaluation of this dose by the CRC (see 
Section 10.1.2 Phase 1b Dose Escalation for full details). If there is a single DLT event in 
each dose cohort before escalation to the next dose cohort then it is possible for a maximum 
of 18 patients (6 per dose cohort) to be enrolled in the phase 1b study. 
Cohort Expansion and RP2D Definition for Phase 1b Study 
Dose cohorts in the phase 1b study will be expanded according to a 3+3 safety evaluation 
design by CRC decision according to the DLT rules presented in Section 10.1.2. This 
design allows for up to 6 patients per dose cohort for a maximum of 18 patients enrolled 
in the study. Alternatively, once 3 patients on a single dose have been reviewed and the 
CRC has given approval to proceed to the next dose cohort then the previous dose cohort 
may be expanded up to 5 patients per cohort to allow for more thorough evaluation of safety 
or immunogenicity. Additional recruitment resulting in up to 5 patients per cohort for 
further safety and immunogenicity evaluation will be at the Sponsor’s discretion. 
The open-label conduct of Phase 1b allows for rapid assessment of the drug-relatedness 
status of any toxicity thereby permitting fast and accurate patient safety evaluation. 
Phase 1b is a multicenter study with up to 18 patients enrolled. Only 15% - 25% of patients 
with ACS test positive for HER2/neu over expression, and of these patients it is expected 
50% will consent and be eligible for Phase 1b. Thus, approximately 180 patients will be 
screened for Phase 1b. 
A total of 3 injections of IMU-131 (P467-CRM – Montanide emulsion) at the specified 
dose will be given to patients (on Days 0, 14, and 35), with chemotherapy cycles every 
21 days starting from Day 14. Chemotherapy will be ceased by the investigator when 
clinically indicated for the care of the patient. Patients will be discontinued from the study 
and cease IMU-131 vaccinations when there is documented evidence of disease progression 
according to the RECIST 1.1 or if unacceptable toxicity occurs (see Section 6.5 Patient 
Withdrawal for complete discontinuation criteria). 
For a representation of the timeline of events in Phase 1b see Figure 1: Timeline for Phase 
1b and for a flow diagram of Phase 1b see Appendix 1: Flow Diagram of Phase 1b. 


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Figure 1: 
Timeline for Phase 1b 
Phase 1b Long Term Maintenance 
Patients completing the Day 56/End of Treatment Visit for Phase 1b will be maintained 
on booster doses of IMU-131 starting from Day 98. A Long Term Maintenance visit will 
occur every 12 weeks and consist of a booster vaccination, a urine pregnancy test, 
collection of blood samples for hematology, serum chemistry and titer kinetic evaluation, 
a physical examination including vital signs (BP, pulse and temperature), a radiographic 
assessment and collection of adverse event and concomitant medication data until the 
patient is no longer participating in long-term maintenance, or IMU-131 has been shown 
to be of no clinical benefit, its development is discontinued or the Sponsor decides to 
terminate the study prematurely. Patients will be discontinued from long term maintenance 
when there is documented evidence of disease progression according to RECIST 1.1 or if 
unacceptable toxicity occurs. 
For details of the procedures and timing of visits during Long Term Maintenance see Table 
2: Schedule of Activities Long Term Maintenance. 
Humoral and cellular immunogenicity data will include P467-specific antibodies (IgG) 
and Her-2- specific antibodies (IgG) in serum samples and vaccine-specific cytokine levels 
as well as analysis of regulatory and effector T and B cells will continue to be collected 
when booster vaccinations are given (i.e. every 12 weeks) during long-term maintenance. 
The dose of booster vaccinations will be determined and vaccination interval confirmed 
by the titer kinetics evaluated in Phase1b. 
Part 2 consists of Phase 2: Evaluation of exploratory clinical activity of IMU-131 
Phase 2 will enroll 36 patients and be conducted in the same centers with the addition of 
new centers, as required, to fulfill recruitment. Phase 2 will have similar 
inclusion/exclusion criteria and be conducted according to a similar schedule of events and 
study procedures. During conduct of the Phase 1b study and prior to the start of Phase 2, 
an amendment to the current protocol will be submitted for ethical and regulatory review. 
The Phase 2 evaluation of clinical activity of IMU-131 will be initiated after approval of 
Screen 
DP1 
DP3 
DP2 
DP = Dose Period 
EOTV = End of Treatment Visit 
SLTM= Start of long-term maintenance 
Day -21 
Day 0 
Day 35 
Day 56 
Day 77 
Day 14 
Day 98 
EOTV 
SLTM 
Vac1 
CC = Chemotherapy Cycle 
Vac2 
CC1 
Vac3 
CC2 
CC3 
CC4 
CC5 
Vac = IMU-131 administration 
Legend : 


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Phase 2 and upon completion of Phase 1b (all cohorts completed through Day 56 and 
selection of a RP2D of IMU-131). 
Phase 2 is an open-label randomized comparison of IMU-131 plus standard of care 
chemotherapy versus standard of care chemotherapy alone. Patients will be randomly 
assigned to either ‘IMU-131 plus chemotherapy’ or ‘chemotherapy alone’ groups. 
Treatment for both groups will begin at the Baseline/Day 0 visit. 
The IMU-131 plus chemotherapy group will receive vaccination of IMU-131 at 
Baseline/Day 0, Day 14, Day 35, Day 77, Day 140 and then every 63 days until disease 
progression. Both the IMU-131 plus chemotherapy group and the chemotherapy alone 
group will receive chemotherapy starting at the Baseline/Day 0 Visit and then every 21 
days for a maximum of 6 cycles as clinically indicated or until disease progression, 
whichever occurs sooner. 
The IDMC will be scheduled to meet after 8, 16 and 24 progression events occur and at 
intervals no less than once per year. Further details of the IDMC meetings and review 
procedures will be contained in the IDMC charter. 
For a representation of the timeline of events in Phase 2 see Figure 2: Timeline for Phase 2 
and for a flow diagram of Phase 2 see Appendix 6: Flow Diagram of Phase 2. 
Figure 2: 
Timeline for Phase 2 
Phase 2 Extension 
The dose escalation during Phase 2 continues the exploration of clinical activity of IMU- 
131 and is an open-label, multicenter, single arm dose escalation study with the same 
inclusion/exclusion criteria as Phase 2 and the same schedule of assessments as Phase 2 
IMU-131+chemotherapy arm. The safety of each dose will be assessed by CRC after at 
least 3 patients have 3 doses of IMU-131 and one cycle of chemotherapy and have 
completed the 35 day DLT window. Two dose cohorts, c
doses of IMU-131, will further characterize the safety, immunogenicity, and clinical 
activity of IMU-131 in combination with chemotherapy. 
Phase 2 dose escalation study will be conducted in Georgia, Serbia, and Ukraine with an 
approximate duration of 24 months: 15 months for recruitment and approximately 
12 months on study. 
The Sponsor may close the study once the last patient completes the end of treatment visit. 


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4.
PATIENT STUDY ENROLMENT AND DISCONTINUATION
The following eligibility criteria are designed to select patients for whom protocol 
treatment is considered appropriate. All relevant medical and non-medical conditions 
should be taken into consideration when deciding whether this protocol is suitable for a 
patient. 
4.1. 
Inclusion Criteria 
Patients must meet all of the following inclusion criteria to be eligible for enrollment into 
the study: 
1. Patient has been informed of the investigational nature of this study and has given
written informed consent in accordance with institutional, local, and national
guidelines;
2. Age
 20 years old; 
3. Life expectancy of at least 12 weeks;
4. Phase 1b: No prior chemotherapy or radiotherapy for advanced gastric or GEJ cancer
within 6 months prior to Day 0;
5. Phase 2/Phase 2 Extension: No prior chemotherapy or radiotherapy for advanced
gastric or GEJ cancer within 3 months prior to Day 0;
6. Metastatic gastric or GEJ adenocarcinoma, or locally advanced disease not amenable
to surgical resection;
7. HER2/neu overexpression (3+ by immunohistochemistry (IHC) or if IHC 2+ confirmed
by fluorescent in situ hybridization [FISH], brightfield double in situ hybridization
[BDISH] or chromogenic in situ hybridization [CISH]). Patients with IHC 2+
expression without confirmation of overexpression by fluorescent in situ hybridization
[FISH], brightfield double in situ hybridization [BDISH] or chromogenic in situ
hybridization [CISH]) may be included in Phase 1b with agreement of Imugene
Limited;
8. Phase 1b: ECOG performance status 0–1;
9. Phase 2/Phase 2 Extension: ECOG performance status 0–2;
10. At least one measurable lesion as defined by RECIST 1.1 criteria. Patients with non-
measurable lesions may be included in Phase1b with agreement of Imugene Limited.;
11. Adequate left ventricular ejection function at baseline, defined as LVEF > 50% by
echocardiogram or MUGA scan (Multi Gated Acquisition Scan);
12. 
9/L, platelet 
9
13. 
 limit of normal 
14. Adequate renal function (creatinine
 1.5 x laboratory ULN); 


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15. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and
other study procedures.
16. Male and female patients of childbearing potential must agree to use a highly effective
method of contraception throughout the study and for at least 28 days following
chemotherapy or 180 days after the last dose of IMU-131 (see Section 4.3 for details).
A patient is of childbearing potential if, in the opinion of the investigator, he/she is
biologically capable of having children and is sexually active.
4.2. 
Exclusion Criteria 
Patients presenting with any of the following will not be included in the study: 
1. Previous treatment with trastuzumab or any other HER2/neu targeting antibody or
agent;
2. Continuous systemic treatment with either corticosteroids (>10 mg daily prednisone
equivalents) or other immunosuppressive medications within 4 weeks prior to first dose
of study treatment. Inhaled or topical steroids and physiological replacement doses of
up to 10 mg daily prednisone equivalents are permitted in the absence of active auto-
immune disease;
3. Prior organ transplant;
4. Phase 1b: Patient not considered a candidate for 5-FU, capecitabine, or cisplatin
chemotherapy;
5. Phase 2/Phase 2 Extension: Patient not considered a candidate for 5-FU, capecitabine,
cisplatin or oxaliplatin chemotherapy;
6. History of documented congestive heart failure; angina pectoris requiring antianginal
medication; evidence of transmural infarction on ECG; poorly controlled hypertension;
clinically significant valvular heart disease; high risk uncontrolled arrhythmias; or New
York Heart Association (NYHA) class II heart disease;
7. If on warfarin (Coumadin®) or other vitamin K antagonists;
8. Concurrent active malignancy except for adequately controlled limited basal cell
carcinoma of the skin;
9. Peripheral neuropathy or hearing loss of NCI CTCAE Grade > 2; 
10. History of uncontrolled seizures, central nervous disorders or psychiatric disability
judged by the investigator to be clinically significant and precluding informed consent,
participation in the study, or adversely affecting compliance to study drugs;
11. Active infection requiring IV antibiotics;
12. Positive for human immunodeficiency virus (HIV) (HIV 1/2 antibodies) or active
hepatitis B (HBsAg reactive) or active hepatitis C (HCV ribonucleic acid [RNA]
qualitative) infection;
13. Pregnant or lactating females;
14. Major surgery within 4 weeks prior to study entry. Minor surgery (excluding diagnostic
biopsy) within 1 week prior to study entry;


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15. Has received a live-virus vaccination within 4 weeks of first study vaccination.
Seasonal flu vaccines that do not contain live virus are permitted;
16. Current or recent (within 4 weeks of first IMU-131 vaccination) treatment with
another investigational drug or participation in another investigational study.
17. Phase 2/Phase 2 Extension: Patients 
with 
a 
known 
diphtheria 
toxoid
hypersensitivity.
4.3. 
Contraception Guidelines 
All male and female patients who, in the opinion of the investigator, are biologically 
capable of having children and are sexually active, must agree to use a highly effective 
method of contraception consistently and correctly for the duration of the active treatment 
period and for at least 28 days following chemotherapy or 180 days after the last dose of 
IMU-131. 
The investigator, in consultation with the patient, will select the most 
appropriate method of contraception for the individual patient from the permitted list of 
contraception methods, and instruct the patient in its consistent and correct use. The 
investigator, at each study visit, will confirm and document consistent and correct use. In 
addition, the investigator will instruct the patient to call immediately if the selected birth 
control method is discontinued or if pregnancy is known or suspected. 
Highly effective methods of contraception are those that, alone or in combination, result in 
a failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) 
and include: 
1. Established use of oral, injected or implanted hormonal methods of contraception
2. Correctly placed intrauterine device (IUD) or intrauterine system (IUS).
3. Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream,
suppository).
4. Male sterilization with appropriately confirmed absence of sperm in the post- 
vasectomy ejaculate.
5. Bilateral tubal ligation or bilateral salpingectomy.
5.
STUDY TREATMENTS
5.1. 
Allocation to Treatment 
In Phase 1b patients will be allocated to treatment in a non-randomized, sequential order. 
Each patient will be administered 3 injections of IMU-131 (P467-CRM197-Montanide 
emulsion), at a single dose level on Days 0, 14, and 35, accompanied by chemotherapy 
cycles every 21 days starting from Day 14. 
In Phase 2, patients who are determined to be eligible for the study will be randomized on 
their  Baseline/Day  0  Visit.  Patients  will  be  allocated  to  receive  IMU-131  plus 
chemotherapy or chemotherapy only in a 1:1 ratio. Randomization will be performed 
centrally and stratified by tumor stage at screening (III vs IV) 


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Patients will be randomized into this open-label study using an Interactive Voice or Web 
Response System (IxRS). The central radiography review will be blinded. The rules 
describing the distribution of data and results will be documented prior to study 
commencement. 
The Phase 2 dose escalation study is an open label and non-randomized with patients 
entering the study sequentially according to the dose level being studied. 
5.2. 
Vaccine Supplies 
 
 
 
The Quality Control Standards and Requirements for the aqueous phase vaccine (P467- 
CRM197) and the adjuvant (Montanide ISA 51 VG) are described in separate release 
protocols/Certificate of Analysis and the required approvals have been obtained. 
5.2.1. 
Formulation and Packaging 
The investigational product, IMU-131, will be supplied as P467-CRM197 (aqueous phase 
vaccine) and Montanide ISA 51 VG (adjuvant) in separate boxes. Each box of P467- 
adapters, two luer-lock syringes, one dosing syringe and needle and one I connector. Each 
box of Montanide contains a single 3 mL vial of Montanide ISA 51 VG. 
Chemotherapy is a standard of care treatment and will be sourced and stored by Pharmacy 
under usual and standard conditions. 
5.2.2. 
Preparation and Dispensing 
Emulsification of IMU-131 vaccine (P467-CRM197) – adjuvant (Montanide ISA 51 VG) 
mixture will be completed by appropriately trained and qualified pharmacy or site staff. 
Training and qualification will be provided by the Sponsor or their delegate and 
documented in the study file. 
 
 
 
 
 
 
Only qualified personnel who are familiar with procedures that minimize undue exposure 
to them and to the environment should undertake the preparation, handling, and safe 
disposal of chemotherapeutic agents. 
Phase 1b 
In Phase 1b, IMU-131 is formulated into either a low, medium or high dose with the 
concentration of each dose remaining constant while the injection volume varies: 


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IMU-131 
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Low dose: 
g (peptide P467 antigen equivalent) P467-CRM197 in 50 µL PBS 
buffer and 50 µL Montanide ISA 51 Sterile adjuvant resulting in a 0.1mL injection 
volume;
Mid dose: 
-CRM197 in 150 µL PBS 
buffer and 150 µL Montanide ISA 51 Sterile adjuvant resulting in a 0.3mL 
injection volume or;
High dose: 
-CRM197 in 250 µL 
PBS buffer and 250 µL Montanide ISA 51 Sterile adjuvant resulting in a 0.5mL 
injection volume.
In Phase 1b, chemotherapy will be prepared and dispensed according to Pharmacy standard 
practice. Chemotherapy will include the following treatments: 
cisplatin, IV (80 mg/m2) and either; 
5-FU, 4000 mg/m2 continuous infusion;
or capecitabine, 2000 mg/m2/day, orally.
Phase 2 
In Phase 2, injections of IMU-131-Montanide emulsion (IMU-
-CRM197 in 250 µL PBS buffer and 250 µL
Montanide ISA 51 Sterile adjuvant resulting in a 0.5mL injection volume, will be given to 
patients in the ‘IMU-131 plus chemotherapy’ group on Days 0, 14, 35, 77, 140 and then 
every 63 days until disease progression. 
In Phase 2, chemotherapy will be prepared and dispensed according to Pharmacy standard 
practice. Chemotherapy will include the following treatments: 
cisplatin, IV (80 mg/m2) and either 5-FU, 4000 mg/m2 continuous infusion 
or capecitabine, 2000 mg/m2/day, orally; 
 
Or oxaliplatin, IV (130 mg/m2) and capecitabine, 2000 mg/m2/day, orally. 
Phase 2 Extension 
In Phase 2 dose escalation, IMU-131-Montanide emulsion (IMU-131 vaccine) is 
P467 antigen equivalent) P467-CRM197 in 500 µL PBS buffer with 500 µL Montanide 
ISA 51 sterile adjuvant resulting in a 1.0 mL injection volume. 
Cohort 1 will be dispensed 100 µg IMU-131-Montanide emulsion. 
Cohort 2 will be dispensed 200 µg IMU-131-Montanide emulsion. 
Refer to the study pharmacy manual for detailed IMU-131 vaccine preparation and 
administration instructions. 
In Phase 2 Extension, chemotherapy will be prepared and dispensed according to Pharmacy 
standard practice. Chemotherapy will include the following treatments: 


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cisplatin, IV (80 mg/m2) and either 5-FU, 4000 mg/m2 continuous infusion 
or capecitabine, 2000 mg/m2/day, orally; 
Or oxaliplatin, IV (130 mg/m2) and capecitabine, 2000 mg/m2/day, orally. 
5.2.3. 
Administration 
Chemotherapy is to be administered according to institution standard practice including all 
pre-medications, concomitant medications and dosing criteria. Dose adjustments and 
delays, and discontinuation based on AEs, patient’s condition, and cumulative toxicities 
are permitted for the clinical care of the patient at the discretion of the investigator. 
Body weight will be determined prior to the start of treatment. Body surface area (BSA: 
based on weight and baseline height) will be calculated prior to starting each 21-day 
chemotherapy cycle. Dose modification will be required for >10% change in BSA, unless 
investigator considers this not appropriate. 
Chemotherapy will be administered in 21-day cycles as tolerated or for any other reason to 
discontinue chemotherapy treatment as determined by the investigator for the clinical care 
of the patient. 
Phase 1b 
IMU-131 administration: 
Patients will be enrolled in cohorts of up to 6 patients at one of three escalating dose levels 
of IMU-131: 
Cohort 1 - 10 µg as a 0.1 mL injection 
Cohort 2 - 30 µg as a 0.3 mL injection 
Cohort 3 - 50 µg as a 0.5 mL injection 
The IMU-131 vaccine will be administered IM into the deltoid region of the upper arm 
with a 0.60 x 25 mm 23G needle on Days 0, 14 and 35. 
Chemotherapy administration: 
Standard of care chemotherapy will be administered as a concomitant treatment to all 
patients as a 21-day regimen starting 14 days after first IMU-131 vaccination. To document 
compliance while away from the clinic, patients will record capecitabine treatment in a 
patient diary. 
Chemotherapy will include the following treatments, the dose and duration of which may 
be varied by the investigator as clinically indicated for the patient: cisplatin, IV (80 mg/m2 
on Day 14, then every 21 days) and either 5-FU, 4000 mg/m2 as continuous infusion (CIV, 
administered as 1000 mg/m2/day for 96 hours on days 14 to 17, then every 21 days) or 
capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice 
daily morning and evening for a total of 2000 mg/m2/day on days 14 to 27, then every 
21 days). 


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Phase 2 
IMU-131 administration: 
Patients in the ‘IMU-131 plus chemotherapy’ group will receive injections of IMU-131 at 
disease progression. 
Phase 2 Extension 
IMU-131 administration: 
A total of 3 injections of IMU-131-Montanide emulsion (IMU-131 vaccine) at a particular 
dose will be given to patients in the Phase 2 dose escalation study on Days 0, 14, and 35, 
and then every 63 days with chemotherapy cycles every 21 days (to a maximum of 6 cycles) 
starting from Day 0 prior to safety assessment by CRC.  
The IMU-131 vaccine will be administered IM into the deltoid region of the upper arm with 
a 25-38mm (1-1.5 inches), 21-23G needle. 
Refer to the study pharmacy manual for detailed IMU-131 vaccine preparation and 
administration instructions. 
Chemotherapy administration in Phase 2 and Phase 2 Extension: 
Patients in both the IMU-131 plus chemotherapy group and the chemotherapy alone group 
will receive chemotherapy starting at the Baseline/Day 0 Visit and then every 21 days 
for a maximum of 6 cycles as clinically indicated or until disease progression, whichever 
occurs sooner. One or more chemotherapy treatments may be varied by dose, frequency or 
discontinued completely as determined by the investigator for the clinical care of the 
patient. 
Chemotherapy will be administered as a concomitant therapy to all patients as a 21-day 
regimen starting at Day 0 and consisting of: cisplatin by intravenous administration at 
80 mg/m2 on the first day of each cycle and either 5-FU, 4000 mg/m2 CIV (administered 
as 1000 mg/m2/day as continuous infusion for 96 hours on days 1 to 4 of each cycle) or 
capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice 
daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle), or 
oxaliplatin, by intravenous administration at 130 mg/m2 on Day 1 of each cycle and 
capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice 
daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle). 
5.2.4. 
Compliance 
Study site staff are responsible for administration of IMU-131. To monitor compliance, 
confirmation of successful emulsification by droplet test will be documented prior to each 
administration of IMU-131 and the exact volume and dose administered will be recorded 
in the CRF. 
To document compliance while away from the clinic, patients will record capecitabine 
treatment in a patient diary. 


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5.3. 
Drug Storage and Drug Accountability 
The vaccine and adjuvant must be stored in a safe and locked place with no access 
for unauthorized personnel. 
The peptide antigen P467-CRM197 must be kept frozen until use in a freezer (< -15oC). 
The adjuvant Montanide ISA 51 VG must be stored in a refrigerator at + 2 - + 8°C. 
Storage conditions stated in the Investigator Brochure (IB) may be superseded by the label 
storage conditions. Ensure the label is always checked for correct storage conditions. 
After approval from Imugene Limited, both used and unused vaccine and adjuvant vials 
will be sent for destruction. The destruction may be performed at the study site using locally 
approved biosafety procedures and documentation. 
5.4. 
Concomitant Medication(s) 
5.4.1. 
Permitted medications 
Participants will follow their oncology care plan. All medications required as part of a 
participant’s normal clinical care for support of their medical conditions are permitted 
during the study, with the exception of prohibited medications listed in Section 5.4.2. All 
concomitant medications must be recorded in the source documentation and in the CRFs 
for the duration of patient participation. 
Treatment with an oral corticosteroid, such as dexamethasone, up to 8 mg daily (24mg 
maximum) during each chemotherapy cycle is allowed if required but may impact the 
development of Her2/neu antibodies. 
5.4.2. 
Prohibited medications 
The following medications/treatments are prohibited during the study: 
Other investigational drug;
Continuous systemic treatment with either corticosteroids (>10 mg daily 
prednisone equivalents) or other immunosuppressive or immuno-modulatory 
medications unless required to treat an immune adverse event. Inhaled or topical 
steroids and physiological replacement doses of up to 10 mg daily prednisone 
equivalents are permitted;
Total doses greater than 24mg dexamethasone equivalent of oral corticosteroids 
per chemotherapy cycle are prohibited.
6.
STUDY PROCEDURES
It is the investigator's responsibility to ensure that the intervals between visits/contacts are 
strictly followed. Every attempt should be made to complete all study visits as outlined in 
the Schedule of Activities. All missed study visits and visits outside the visit window are 
considered protocol deviations. 


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Please refer to Table 1 Schedule of Activities: Phase 1b which lists the visits, permissible 
visit windows and required study procedures. 
For details of the procedures and timing of visits during Long Term Maintenance see Table 
2: Schedule of Activities Long Term Maintenance. 
Please refer to Table 3 Schedule of Activities: Phase 2 and Phase 2 Extension, which lists 
the visits, permissible visit windows and required study procedures. 
6.1. 
Screening (Phase 1b and Phase 2/Phase 2 Extension) 
Patients agreeing to participate in the study will sign the informed consent documents. A 
patient screening number comprised of a unique site number and sequential screening 
number will be issued at the time of consent. The reason for all screen failures will be 
documented. The screening assessments should occur within 3 weeks prior to starting 
treatment. 
Screening will occur across at least 2 clinic visits. At the first screening visit the patient 
will be asked to provide consent, the inclusion/exclusion criteria will be checked and 
screening for HER2/neu overexpression will be completed. All other screening procedures 
will be conducted at subsequent screening visits. 
Procedures will be performed in the following order. 
A) First screening visit:
Obtain Informed Consent; 
Check inclusion/exclusion criteria; 
Use archival tissue, previous HER2 overexpression results or obtain biopsy for 
HER2 overexpression confirmation and intra-tumor markers. 
B) Subsequent screening visits:
Medical history (including cancer history), prior and concomitant medications and 
procedures, and demographics will be documented; 
Physical examination; 
Height, weight, and vital signs (blood pressure, temperature and heart rate); 
ECOG performance score; 
Radiographic assessment (for Baseline assessment, allowed up to 14 days prior to 
Day 0); 
Cardiac assessment by echocardiography or MUGA scan and 12-lead ECG; 
Urine pregnancy test (female); 
Blood sample for hematology, serum chemistry, HIV and hepatitis B and C; 
Blood sample for cellular immunology (Phase 2 Extension only). 
If a patient’s laboratory results do not meet the eligibility criteria at Screening, the 
laboratory assessment may be repeated within the Screening Period. 


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6.1.1. 
Re-Screening 
Phase 1b 
Patients are able to be re-screened when the following situations are present: Dose cohort 
not open; Drug supply not available at site; Unable to attend/schedule first dose visit; Tests 
or procedures are not completed in screening period (i.e., patients who miss their 21-day 
screening window). For any other situation, agreement must be obtained from Imugene 
Limited before performing re-screening. 
If a patient has been entered in the CRF as a “screen failure” they cannot be re-screened. 
A new ICF must be signed before re-screening can commence. Re-screened patients will 
keep the same subject number. Screening procedures and test results/eligibility checks will 
be updated as part of re-screening. 
Phase 2/Phase 2 Extension 
Patients may be re-screened when the following situations are present: Drug supply not 
available at site; Unable to attend/schedule first dose visit; Tests or procedures are not 
completed in screening period (i.e., patients who miss their 21-day screening window). For 
any other situation, agreement must be obtained from Imugene Limited before performing 
re-screening. 
Patients who have been randomized cannot be re-screened. 
A new ICF must be signed before re-screening can commence. Re-screened patients will 
keep the same screening number. Screening procedures and test results/eligibility checks 
will be updated as part of re-screening. 
Only Serious Adverse Events (SAEs) caused by a protocol-mandated intervention (e.g., 
invasive procedures such as biopsies, discontinuation of medications) should be reported 
from date of first informed consent to initiation of study drug(s).  
6.2. 
Phase 1b Study Period 
6.2.1. 
Phase 1b Vaccination procedure (Day 0, 14 and 35) 
All vaccinations must be administered in an appropriate medical facility equipped for 
immediate intervention in the event of an allergic reaction. 
Preparation of IMU-131 is to be conducted precisely according to instruction in Section 
5.2.2 Preparation and Dispensing. Patients will be vaccinated on days 0, 14 and 35 
respectively. Prior to vaccination patients will undergo complete physical examinations, 
including vital signs (blood pressure, pulse, temperature). IMU-131 vaccine should be 
administered intramuscularly (IM) into the deltoid region of the upper arm with a 0.60 x 
25 mm 23G needle. The vaccination site should be disinfected with a skin disinfectant 
(e.g., 70% alcohol) prior to vaccination of study drug IM. The vaccine must not be injected 
into blood vessels and the Medical Professional administering the injection must confirm 
IM placement via a “negative” blood return on a “pull back” check before injecting IMU-
131. 


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Patients will be observed for at least 30 minutes after vaccination, with appropriate medical 
treatment readily available in case of a rare anaphylactic reaction following the 
administration. Any reactions that occur during this time must be recorded by the 
investigator in the CRF. Thirty minutes (+/- 10 min) after vaccination, the patient’s 
temperature will be recorded. 
Patients will be instructed to contact the investigator immediately should they manifest any 
signs or symptoms they perceive as serious. 
6.2.2. 
Phase 1b Dose Period 1 (Day 0 and Day 2) 
Dose Period 1 consists of Day 0/Baseline and Day 2. There are no allowable visit windows 
for Dose Period 1. 
Day 0/Baseline procedures will be performed in the following order: 
Physical examination;
Weight, and vital signs (blood pressure, temperature and heart rate);
Urine pregnancy test (female);
Blood sample for hematology and serum chemistry tests;
Blood sample for immunology tests;
Administer IMU-131 vaccination;
Record body temperature 30 (+/-10) minutes after vaccination;
Record concomitant treatments;
Record adverse events.
Day 2 procedures will be performed in the following order: 
Vaccination site evaluation for local effects;
Record concomitant treatments;
Record adverse events.
6.2.3. 
Phase 1b Dose Period 2 (Day 14 and Day 16) 
Dose Period 2 consists of Day 14 and Day 16. The visit window for Dose Period 2 is +/- 3 
day of the scheduled visit. 
Day 14 procedures will be performed in the following order: 
Physical examination;
Weight, and vital signs (blood pressure, temperature and heart rate);
Urine pregnancy test (female);
Blood sample for hematology and serum chemistry tests;
Blood sample for immunology tests;


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Administer IMU-131 vaccination;
Record body temperature 30 (+/-10) minutes after vaccination;
Record concomitant treatments;
Record adverse events;
Initiate chemotherapy cycle 1.
Day 16 procedures will be performed in the following order: 
Vaccination site evaluation for local effects;
Record concomitant treatments;
Record adverse events.
6.2.4. 
Phase 1b Dose Period 3 (Day 35 and Day 37) 
Dose Period 3 consists of Day 35 and Day 37. The visit window for Dose Period 3 is +/- 3 
days of the scheduled visit. 
Day 35 procedures will be performed in the following order: 
Physical examination;
Weight, and vital signs (blood pressure, temperature and heart rate);
Urine pregnancy test (female);
Blood sample for hematology and serum chemistry tests;
Administer IMU-131 vaccination;
Record body temperature 30 (+/-10) minutes after vaccination;
Record concomitant treatments;
Record adverse events;
Initiate chemotherapy cycle 2.
Day 37 procedures will be performed in the following order: 
Vaccination site evaluation for local effects;
Record concomitant treatments;
Record adverse events.
6.2.5. 
Phase 1b End of Treatment Visit (Day 56) 
The end of treatment visit occurs on Day 56. The allowable visit window for this visit is 
+/- 3 days. 
End of treatment/Day 56 procedures will be performed in the following order: 
Physical examination;


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Protocol Identifier: 
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Weight, and vital signs (blood pressure, temperature and heart rate);
Blood sample for hematology and serum chemistry tests;
Blood sample for immunology tests;
Cardiac assessment by echocardiography or MUGA scan and 12-lead ECG;
Radiographic assessment;
Record concomitant treatments;
Record adverse events;
Initiate chemotherapy cycle 3.
6.2.6. 
Phase 1b chemotherapy only visit (Day 77) 
Day 77 is for continuation of chemotherapy, as determined by the study investigator. A 
visit window of +/- 7 days is allowable. 
Day 77 procedures will be performed in the following order: 
Physical examination;
Weight, and vital signs (blood pressure, temperature and heart rate);
Blood sample for hematology and serum chemistry tests;
Record concomitant treatments;
Record adverse events;
Initiate chemotherapy cycle 4.
6.2.7. 
Phase 1b Follow-up Post-Withdrawal Visit (30 – 40 days after last vaccination) 
A visit window of - 2 days to +16 days is allowable. 
When the patient is withdrawn during either Phase 1b or Long Term Maintenance this 
visit occurs 30 – 40 days after the last vaccination. The subject summary page of the CRF 
should be completed after this visit has occurred. 
Follow-up post withdrawal procedures will be performed in the following order: 
Physical examination;
Weight, and vital signs (blood pressure, temperature and heart rate);
Urine pregnancy test (female);
Record concomitant treatments (medications and procedures);
Record adverse events.
6.2.8. 
Phase 1b Unscheduled Visit 
Unscheduled visits may be conducted at any time during Phase 1b or Long Term 
Maintenance by the investigator if clinically indicated for the care of the patient. 


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An unscheduled visit may include any of the protocol required assessments listed in Section 
7: Phase 1b Assessments. The exact assessments conducted at the unscheduled visit will be 
specified by the investigator and recorded in the CRF. Additional tests and procedures may 
be performed at the unscheduled visit for the clinical care of the patient after discussion 
with, and agreement of, the medical monitor. 
6.3. 
Phase 1b Long Term Maintenance of Phase 1b patients (Day 98 
onwards) 
Patients completing the End of Treatment/Day 56 assessment in Phase 1b will move into 
long term maintenance starting at Day 98. Long term maintenance will continue until the 
patient is no longer participating in the study, or IMU-131 has been shown to be of no 
clinical benefit, its development is discontinued or the Sponsor decides to terminate the 
study prematurely. Patients will discontinue participation in long term maintenance when 
there is documented evidence of disease progression according to RECIST 1.1 response 
criteria or if unacceptable toxicity occurs. The last long term maintenance visit prior to 
discontinuation will be recorded as the end of treatment visit for long term maintenance. 
The Phase 1b follow-up post withdrawal visit (Section 6.2.7) will be conducted 30 – 40 
days after the last vaccination during long term maintenance. 
In addition to booster vaccinations most likely every 12 weeks each Long Term 
Maintenance visit will include a urine pregnancy test, collection of blood samples for 
hematology, serum chemistry and titer kinetic evaluation, a physical examination including 
vital signs (BP, pulse and temperature), a radiographic assessment and collection of adverse 
event and concomitant medication data. For details of the procedures and timing of visits 
during Long Term Maintenance see Table 2: Schedule of Activities Long Term 
Maintenance. 
Humoral and cellular immunogenicity data will include P467-specific antibodies (IgG) and 
Her-2- specific antibodies (IgG) in serum samples and vaccine-specific cytokine levels as 
well as analysis of regulatory and effector T and B cells will continue to be collected when 
booster vaccinations are given (i.e. every 12 weeks) during long-term maintenance. The 
dose of booster vaccinations will be determined and vaccination interval confirmed by the 
titer kinetics evaluated in Phase1b, details of which will be provided for ethical and 
regulatory review as an amendment to this protocol. 
6.4. 
Phase 2 and Phase 2 Extension Study Period 
6.4.1. 
Phase 2 and Phase 2 Extension Vaccination procedure 
All vaccinations must be administered in an appropriate medical facility equipped for 
immediate intervention in the event of an allergic reaction. 
Preparation of IMU-131 is to be conducted precisely according to instruction in Section 
5.2.2 Preparation and Dispensing. Prior to vaccination patient’s vital signs (blood pressure, 
pulse, temperature) will be measured. IMU-131 vaccine should be administered 
intramuscularly (IM) into the deltoid region of the upper arm with a 25-38mm 
(1-1.5 inches), 21-23G needle needle. The vaccination site should be disinfected with a 
skin disinfectant (e.g., 70% alcohol) prior to vaccination of study drug IM. The vaccine 
must not be injected into blood vessels and the Medical Professional administering the 


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injection must confirm IM placement via a “negative” blood return on a “pull back” check 
before injecting IMU-131. 
Patients will be observed for at least 30 minutes after vaccination, with appropriate medical 
treatment readily available in case of a rare anaphylactic reaction following the 
administration. Any reactions that occur during this time must be recorded by the 
investigator in the CRF. Thirty minutes (+/- 10 min) after vaccination, the patient’s 
temperature will be recorded. 
Patients will be instructed to contact the investigator immediately should they manifest any 
signs or symptoms they perceive as serious. 
6.4.2. 
Phase 2 and Phase 2 Extension Baseline/Day 0 
There is no allowable visit window for Baseline/Day 0. Day 0/Baseline procedures should 
be performed in the following order: 
Blood sample for hematology and serum chemistry (Screening safety lab samples 
taken within 72 hours of first study treatment do not need to be repeated on Day 
0);
Blood sample for humoral and cellular immunology;
Blood sample for exploratory endpoints;
Weight, and vital signs (blood pressure, temperature and heart rate);
Urine pregnancy test (female);
Physical examination;
ECOG performance score;
Radiographic assessment (Allowed during screening period - up to 14 days prior 
to Day 0)
Administer IMU-131 vaccination and record body temperature 30 (+/-10) minutes 
after vaccination (only for patients in IMU-131 plus chemotherapy group);
Record concomitant treatments;
Record adverse events;
Initiate chemotherapy cycle 1.
6.4.3. 
Phase 2 and Phase 2 Extension Week2/Day 14 (only for patients in IMU-131 plus 
chemotherapy cohorts) 
The visit window for Day 14 is +/- 3 days of the scheduled visit. Day 14 procedures should 
be performed in the following order: 
Weight, and vital signs (blood pressure, temperature and heart rate);
Urine pregnancy test (female);
Administer IMU-131 vaccination;
Record body temperature 30 (+/-10) minutes after vaccination;


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Record concomitant treatments;
Record adverse events.
6.4.4. 
Phase 2 and Phase 2 Extension Week 3/Day 21 
The visit window for Day 21 is +/- 3 days of the scheduled visit. Day 21 procedures should 
be performed in the following order: 
Blood sample for hematology and serum chemistry;
Blood sample for humoral immunology;
Weight, and vital signs (blood pressure, temperature and heart rate);
Urine pregnancy test (female);
Physical examination;
Record concomitant treatments;
Record adverse events;
Initiate chemotherapy cycle 2.
6.4.5. 
Phase 2 and Phase 2 Extension Week 5/Day 35 (only for patients in IMU-131 
plus chemotherapy cohorts) 
The visit window for Day 35 is +/-3 days of the scheduled visit. Day 35 procedures should 
be performed in the following order: 
Weight, and vital signs (blood pressure, temperature and heart rate);
Urine pregnancy test (female);
Administer IMU-131 vaccination;
Record body temperature 30 (+/-10) minutes after vaccination;
Record concomitant treatments;
Record adverse events.
6.4.6. 
Phase 2 and Phase 2 Extension Week 6/Day 42 
The visit window for Day 42 is +/- 3 days of the scheduled visit. Day 42 procedures should 
be performed in the following order: 
Blood sample for hematology and serum chemistry;
Blood sample for humoral immunology;
Weight, and vital signs (blood pressure, temperature and heart rate);
Urine pregnancy test (female);
Physical examination;
Radiographic assessment;
Record concomitant treatments;


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Record adverse events;
Initiate chemotherapy cycle 3.
6.4.7. 
Phase 2 and Phase 2 Extension Week 9/Day 63 
The visit window for Day 63 is +/- 7 days of the scheduled visit. Day 63 procedures should 
be performed in the following order: 
Blood sample for hematology and serum chemistry;
Blood sample for humoral immunology;
Weight, and vital signs (blood pressure, temperature and heart rate);
Urine pregnancy test (female);
Physical examination;
Record concomitant treatments;
Record adverse events;
Initiate chemotherapy cycle 4.
6.4.8. 
Phase 2 and Phase 2 Extension Week 11/Day 77 (only for patients in IMU-131 
plus chemotherapy cohorts) 
The visit window for Day 77 is +/- 7 days of the scheduled visit. Day 77 procedures should 
be performed in the following order: 
Weight, and vital signs (blood pressure, temperature and heart rate);
Urine pregnancy test (female);
Administer IMU-131 vaccination;
Record body temperature 30 (+/-10) minutes after vaccination;
Record concomitant treatments;
Record adverse events.
6.4.9. 
Phase 2 and Phase 2 Extension Week 12/Day 84 (Repeat every 12 weeks/84 days) 
The visit window for Day 84 is +/- 7 days of the scheduled visit. Day 84 procedures should 
be performed in the following order: 
Weight, and vital signs (blood pressure, temperature and heart rate);
Blood sample for hematology and serum chemistry;
Blood sample for humoral and cellular immunology;
Blood sample for exploratory endpoints;
Urine pregnancy test (female);
Physical examination;
ECOG performance score;


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Cardiac assessment by echocardiography or MUGA scan and 12-lead ECG;
Radiographic assessment;
Optional tumor biopsy sample ( at Day 84);
Record concomitant treatments;
Record adverse events;
Initiate chemotherapy cycle 5.
6.4.10. 
Phase 2 and Phase 2 Extension Week 15/Day 105 
The visit window for Day 105 is +/- 7 days of the scheduled visit. Day 105 procedures 
should be performed in the following order: 
Blood sample for hematology and serum chemistry;
Weight, and vital signs (blood pressure, temperature and heart rate);
Urine pregnancy test (female);
Physical examination;
Record concomitant treatments;
Record adverse events;
Initiate chemotherapy cycle 6.
6.4.11. 
Phase 2 and Phase 2 Extension Week 18/Day 126 (Repeat every 12 weeks/84 
days) 
The visit window for Day 126 is +/- 7 days of the scheduled visit. Day 126 procedures 
should be performed in the following order: 
Blood sample for hematology and serum chemistry;
Blood sample for humoral immunology;
Weight, and vital signs (blood pressure, temperature and heart rate);
Urine pregnancy test (female);
Physical examination;
Radiographic assessment;
Record concomitant treatments;
Record adverse events;
6.4.12. 
Phase 2 and Phase 2 Extension Week 20/Day 140 (Repeat every 9 week/63 days - 
only for patients in IMU-131 plus chemotherapy cohorts) 
The visit window for Day 140 is +/- 7 days of the scheduled visit. Day 140 procedures 
should be performed in the following order: 
Weight, and vital signs (blood pressure, temperature and heart rate);


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Urine pregnancy test (female);
Administer IMU-131 vaccination;
Record body temperature 30 (+/-10) minutes after vaccination;
Record concomitant treatments;
Record adverse events.
6.4.13. 
Phase 2 and Phase 2 Extension End of Treatment (EoT) Visit 
When progressive disease or withdrawal from study has been confirmed, the EoT visit 
will be conducted at least 28 Days (+/- 7) after last dose of study medication. An optional 
post-progression tumor biopsy sample will be requested from patients and may be provided 
at any time post progression. EoT visit procedures should be performed in the following 
order: 
Weight, and vital signs (blood pressure, temperature and heart rate);
Blood sample for hematology and serum chemistry;
Blood sample for humoral and cellular immunology;
Blood sample for exploratory endpoints;
Urine pregnancy test (female);
Physical examination;
ECOG performance score;
Cardiac assessment by echocardiography or MUGA scan and 12-lead ECG;
Record concomitant treatments;
Record adverse events (AEs to be checked at least 28 days after last study 
treatment per Section 9.2: Reporting Period).
6.4.14. 
Phase 2 Post-Treatment Follow-up Visit (Every 42 days after EoT visit) 
This visit may be conducted via phone, email, review of medical records or via publicly 
available information. A visit window of +/- 7 days is allowable. 
Radiographic assessment (only for patients who withdrew from study before 
progressive disease was confirmed);
Record survival follow-up assessment;
Record post-study anti-cancer treatment.
6.4.15. 
Phase 2 and Phase 2 Extension Unscheduled Visit 
Unscheduled visits may be conducted at any time during Phase 2 by the investigator if 
clinically indicated for the care of the patient. 
An unscheduled visit may include any of the protocol required assessments listed in Section 
8: Phase 2 Assessments. The exact assessments conducted at the unscheduled visit will be 
specified by the investigator and recorded in the CRF. Additional tests and procedures may 


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be performed at the unscheduled visit for the clinical care of the patient after discussion 
with, and agreement of, the medical monitor. 
6.5. 
Patient Withdrawal 
6.5.1. 
Main discontinuation criteria 
Patients will discontinue study treatment and complete the study according to the study 
protocol when there is documented evidence of disease progression according to RECIST 
1.1 response criteria or if unacceptable toxicity occurs. Patients may discontinue study 
treatment and be withdrawn from the study prematurely based on symptomatic clinical 
disease progression without documented radiographic evidence only after discussion with 
the Sponsor/medical monitor. 
6.5.2. 
Contraindications to repeated vaccination 
If any of the following adverse events arise during the study they constitute 
contraindications to further administration of IMU-131, and patients should discontinue 
IMU-131 treatment permanently and be withdrawn from the study immediately, with 
appropriate safety follow-up by the investigator until resolution of the event, as with any 
adverse event (see Section 9: Adverse Event Reporting): 
Anaphylactic reaction following the administration of vaccine(s).
Any clinically relevant immunosuppressive or immuno-deficient condition.
The following events constitute contraindications to administration of IMU-131. If an 
adverse event, the event must be reported and the patient followed as with any adverse 
event. Withdrawal of patients experiencing the following events is at the discretion of the 
investigator as indicated below: 
Acute illness at the time of vaccination. Acute illness is defined as the presence 
of a moderate or severe illness with or without fever. All vaccines can be 
administered to persons with a minor illness such as diarrhea, mild upper 
respiratory infection with or without low-grade febrile illness, i.e., temperature 
<38°C. Withdrawal is at the discretion of the investigator if acute illness will not 
resolve in sufficient time to allow for vaccination schedule to continue.
Temperature > 38°C at the time of vaccination. Withdrawal is at the discretion of 
the investigator if raised temperature will not resolve in sufficient time to allow 
for vaccination schedule to continue.
6.5.3. 
Additional Discontinuation Criteria 
Patients must discontinue from the study if any of the following additional criteria are met: 
The patient requests discontinuation from the study;
The Sponsor stops the study;
The Sponsor stops the patient’s participation in the study;
The patient becomes pregnant during the study period.


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Patients may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or Sponsor for safety or 
behavioral reasons, or the inability of the patient to comply with the protocol required 
schedule of study visits or procedures at a given study site. 
If a patient does not return for a scheduled visit, every effort should be made to contact the 
patient. In any circumstance, every effort should be made to document patient outcome, if 
possible. The investigator should inquire about the reason for withdrawal, request the 
patient to return for a final visit, if applicable, and follow-up with the patient regarding any 
unresolved adverse events (AEs). 
If the patient withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected. The Sponsor may retain and continue to use any data collected before such 
withdrawal of consent. 
7.
PHASE 1B ASSESSMENTS
Every effort should be made to ensure that protocol required tests and procedures are 
completed as described. 
7.1. 
Phase 1b Physical Examination (Screening, Days 0, 14, 35, 56, 77, 98, 
LTM visits) 
The physical examination will include an evaluation of body systems (e.g. cardiovascular, 
gastrointestinal, neurological, head and neck, respiratory, dermatology). Evaluation for pre- 
existing condition that might exclude the patient from eligibility or could interfere with the 
patient’s participation and compliance with the protocol should be performed at Screening. 
7.2. 
Phase 1b Height, Weight and Vital Signs (Screening, Days 0, 14, 35, 56, 
77, 98, LTM visits) 
Body height (at screening visit only), weight, and vital signs (blood pressure, pulse and 
temperature) will be measured. 
7.3. 
Phase 1b Radiographic Assessment (Screening, Days 56, 98, LTM 
visits) 
For all patients, a radiographic assessment will be performed at Screening (for inclusion 
criteria assessment), and at Day 56, Day 98 and at long term maintenance visits until disease 
progression. 
Computed Tomography (CT) scan of the chest abdomen and pelvis with contrast should be 
performed. MRI of the abdomen and pelvis with contract and non-contrast CT chest 
may be done in patients with iodine contrast dye allergy or if lesions cannot be visualized 
on CT scan. 
Radiographic assessments must be performed within +/- 2 weeks of the planned visit date. 
Additional radiographic assessment may be performed as part of a Phase 1b Unscheduled 


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Visit (Section 6.2.8) at the discretion of the investigator as clinically indicated. Assessment 
of the tumor will include evaluation according to the RECIST 1.1. 
7.4. 
Phase 1b Cardiac Assessment (Screening, Day 56) 
Cardiac assessment of suitability for inclusion in the study and on Day 56 will be performed 
by the study investigator and be based on assessment of medical history, physical 
examination, 12-lead ECG results and evaluation of left ventricular ejection fraction 
(LVEF) by echocardiography or MUGA scan. Cardiology consult may be sought by the 
investigator if required to confirm suitability for inclusion in the study. 
7.5. 
Phase 1b Laboratory Assessments 
Hematology and serum chemistry analyses will be performed by an accredited central 
laboratory. Immunological analysis will be performed by an accredited specialist 
immunology laboratory. 
Central laboratory results should be reviewed by the principal investigator (PI) or another 
qualified study staff member as soon as received. Subject management is dependent upon 
close review of the laboratory data. 
Unscheduled and repeat laboratory tests will also be performed by the central 
laboratory. However, if the turnaround time from the central laboratory is not sufficiently 
rapid for clinical management of the subject, local laboratory test results may be used to 
make the necessary clinical judgments. 
A Central Laboratory Manual with instructions on specimen collection, processing, storing, 
and shipping will be provided to all participating sites. 
7.5.1. 
Phase 1b Safety Laboratory Assessments (Screening, Days 0, 14, 35, 56, 77, 98, 
LTM visits) 
Blood samples of approximately 10 mL in total for the assessment of hematological and 
serum chemistry parameters will be collected and processed in accordance with the central 
laboratory study manual. 
All hematology and serum chemistry samples will be submitted by the Investigator to the 
certified central laboratory for analysis. Blood samples for hematology and serum 
chemistry will be prepared using standard procedures. 
Safety laboratory panels are defined as follows: 
Human immunodeficiency virus (HIV 1/2 antibodies), hepatitis B (HBsAg reactive) and 
hepatitis C (HCV ribonucleic acid [RNA] qualitative) (at screening only). 
Hematology: Hematology to include CBC, including RBC count, hemoglobin, hematocrit, 
reticulocyte count, WBC count with differential (neutrophils, bands, eosinophils, basophils, 
lymphocytes, monocytes, and other cells), platelet count, C-reactive protein (CRP), IL-1, 
IL-6, IL8, TNF-a, CXCL-9 and CXCL-10. 


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Serum Chemistry: BUN or urea, creatinine, sodium, chloride, potassium, magnesium, 
bicarbonate, calcium, phosphorus, total protein, albumin, alkaline phosphatase, glucose, 
total bilirubin, direct and indirect bilirubin, lactate dehydrogenase (LDH), cholesterol, uric 
acid, triglyceride levels, gamma glutamyl transpeptidase (GGT), AST, and ALT. 
Abnormalities in clinical laboratory tests that are considered clinically significant by the 
investigator will be recorded on the laboratory CRF page. If abnormal laboratory results 
are also considered an adverse event, then a corresponding AE CRF will also be completed. 
If values after the first dose meet criteria defining them as serious, they must be reported 
as SAEs (see Section 9.12.1: Serious Adverse Event Reporting Requirements). 
7.5.2. 
Phase 1b Immunologic Assessments (Screening, Days 0, 14, 35, 56, 77, 98, LTM 
visits) 
Prior to each vaccination a 1 x 8 mL whole blood sample for humoral immunity will be 
obtained from the patient at Days 0, 14, 35, 56, 77, 98 and at LTM visits. Additionally, on 
Days 0, 56 and at each LTM visit, 5 x 8 mL heparinized blood samples will be collected 
for PBMC isolation and analysis of cellular parameters. 
All blood samples for immunological assessment will be collected and processed at the 
study site according to the Central Laboratory Manual. These immunological blood 
samples will be collected by, and stored at, the central laboratory before bulk shipment to 
the specialist immunology laboratory at the 
 
 for analysis. 
7.5.3. 
Phase 1b HER2/neu overexpression (Screening) 
Confirmation of HER2/neu overexpression is required for inclusion in this study. However, 
patients with IHC HER2 ++ expression without confirmation of overexpression by 
fluorescent in situ hybridization [FISH] brightfield double in situ hybridization [BDISH] 
or chromogenic in situ hybridization [CISH]) may be included in Phase 1b with agreement 
of Imugene Limited. 
A previous pathology result confirming HER2/neu overexpression is acceptable. If analysis 
of a tumor biopsy is required for confirmation of HER2/neu overexpression then this may 
be achieved via analysis of a fresh or archived tissue sample. Results are to be entered into 
the respective CRF. 
If a biopsy sample is used to determine HER2/neu overexpression then analysis of intra- 
tumor T cells for CD8+, CD4+, Th1, Th2, Tregs (Foxp3+ CD25+) will also be performed 
if these analyses are available at the pathology lab conducting HER2/neu overexpression 
analysis. 
HER2/neu analysis will be conducted at each center’s local pathology laboratory by 
immunohistochemistry (IHC) and fluorescent in situ hybridization [FISH] or chromogenic 
in situ hybridization [CISH] if IHC result is equivocal. 
Using the IHC method an unequivocal result of HER2 overexpression is defined as HER2 
+++, an equivocal result is defined as HER2 ++, and a negative result is defined as HER2 
+. If equivocal result (IHC HER2 ++) then additional analysis via FISH or CISH will be 


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conducted for confirmation of HER2 overexpression. The definition of FISH or CISH 
positivity in gastric or gastro–esophageal junction cancer is a HER2: chromosome 17 ratio 
7.5.4. 
Phase 1b ECOG performance grade (Screening) 
The ECOG performance grade for screening evaluation should be determined using the 
criteria defined in Appendix 3: ECOG Performance Status Scale. 
7.6. 
Phase 1b Vaccination site evaluation (Days 2, 16, 37) 
The purpose of vaccination site evaluation is to determine the nature and frequency of 
local/vaccination site reactions. The vaccination site should be evaluated for local effects 
of 
the 
vaccine 
injection 
including 
pain, 
tenderness, 
erythema/redness 
and 
swelling/induration (see Section 9.7.1 Local (injection site) Adverse Event Intensity for 
further details). All local vaccination site effects are to be reported in the CRF and graded 
according to Table 4: Grading of Local Adverse Event Intensity presented in Section 9.7.1. 
Photographs will be taken during vaccination site evaluation if there are visible local 
injection site reactions. 
7.7. 
Phase 1b Pregnancy Test (Screening, Days 0, 14, 35, 98, LTM visits) 
For female patients of childbearing potential, a urine pregnancy test, with sensitivity of at 
least 25 mIU/mL, will be performed immediately before administration of each vaccine 
dose. A negative pregnancy test result is required before the patient may receive the 
investigational product. If urine pregnancy test is positive then confirmation of pregnancy 
will be by BHCG blood test. If BHCG blood test is negative then vaccination schedule may 
resume. Pregnancy tests may also be repeated as per request of IRB/IECs or if required by 
local regulations. 
8.
PHASE 2 AND PHASE 2 EXTENSION ASSESSMENTS
Every effort should be made to ensure that protocol required tests and procedures are 
completed as described. 
8.1. 
Assessments via Telemedicine 
Telemedicine uses advanced telecommunication technologies to exchange health 
information and provide health care services across geographic, social, and other barriers. 
Where circumstances allow, and where additional flexibility is required due to restricted 
patient access to the study clinic or personnel, telemedicine technology may be used to 
collect study data to supplement study assessments. For example, visits may be conducted 
over several days within each visit window, with suitable assessments being completed 
using telemedicine technology with the remaining assessments being completed during a 
physical clinic visit. Examples of study assessments which may be completed using 
telemedicine technology include documenting concomitant treatments and adverse events, 
ECOG performance grade, and survival follow-up. 


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8.2. 
Phase 2 and Phase 2 Extension Physical Examination (Screening, 
Baseline, Days 21, 42, 63, 84, 105, 126 then every 42 days and EoT visit) 
The physical examination will include an evaluation of body systems (e.g. cardiovascular, 
gastrointestinal, neurological, head and neck, respiratory, dermatology). After the Baseline 
physical examination, a symptom-directed physical examination is allowed at subsequent 
visits at the investigator’s discretion. 
8.3. 
Phase 2 and Phase 2 Extension Height, Weight, Vital Signs, 
Concomitant Medications, Concomitant Procedures and Adverse 
Events (at each study visit, excluding post-treatment follow-up visits) 
Body height (at screening visit only), weight, and vital signs (blood pressure, pulse and 
temperature) will be measured and concomitant medications, concomitant procedures and 
adverse events will be documented. 
8.4. 
Phase 2 and Phase 2 Extension Radiographic Assessment (Baseline, 
Days 42, 84, 126 then every 42 days) 
For all patients a radiographic assessment will be performed at Baseline (assessment 
allowed up to 14 days before Baseline Visit), Days 42, 84, 126 then every 42 days until 
disease progression. Assessment of the tumor will include evaluation according to RECIST 
1.1. 
In the Phase 2 extension, a repeat scan may be performed as an unscheduled visit at the 
investigator’s discretion to confirm progression 4-6 weeks after the date of the original scan 
indicating progression. If progression is confirmed the original date of progression will be 
used for disease assessment. 
8.5. 
Phase 2 and Phase 2 Extension Cardiac Assessment (Screening, Day 84 
then every 84 days and EoT visit) 
Cardiac assessment to be performed at Screening, on Day 84 then every 84 days and at EoT 
visit. It will be performed by the study investigator and be based on assessment of medical 
history, physical examination, 12-lead ECG results and evaluation of left ventricular 
ejection fraction (LVEF) by echocardiography or MUGA scan. 
8.6. 
Phase 2 and Phase 2 Extension Laboratory Assessments 
Hematology and serum chemistry analyses will be performed by an accredited local 
laboratory. Serum predication markers of tumor progression and intra-tumor T cell and 
biomarker analysis will be performed by an accredited central laboratory. Humoral and 
cellular immunological analysis will be performed by an accredited specialist central 
immunology laboratory. 
Unused blood /serum and/or tissue samples collected during the study from patients who 
have signed an appropriate informed consent form may be stored and used for future 
research.  The coded samples may be stored up to 15 years after the clinical study ends. A 
patient may contact the investigator to have their unused samples destroyed at any time 


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during the storage period. Results from the future use studies will not be shared with 
patients. 
1) Safety Laboratory Assessments (Screening, Baseline, Days 21, 42, 63, 84,
105, 126 then every 42 days and EoT visit)
Blood samples of approximately 10 mL per visit for the assessment of hematological and 
serum chemistry parameters will be collected and processed in accordance with local 
laboratory procedures and reference ranges. 
Safety laboratory panels are defined as follows: 
Human immunodeficiency virus (HIV 1/2 antibodies), hepatitis B (HBsAg reactive) and 
hepatitis C (HCV ribonucleic acid [RNA] qualitative) (at screening only). 
Hematology: Hematology to include CBC, including RBC count, hemoglobin, hematocrit, 
reticulocyte count, WBC count with differential (neutrophils, bands, eosinophils, basophils, 
lymphocytes, monocytes, and other cells), platelet count, and C-reactive protein (CRP). 
Serum Chemistry: BUN or urea, creatinine, sodium, chloride, potassium, magnesium, 
bicarbonate, calcium, phosphorus, total protein, albumin, alkaline phosphatase, glucose, 
total bilirubin, direct and indirect bilirubin, lactate dehydrogenase (LDH), cholesterol, uric 
acid, triglyceride levels, gamma glutamyl transpeptidase (GGT), AST, and ALT. 
2) Exploratory Endpoint Laboratory Assessments (Baseline, Days 84 then
every 84 days and EoT visit)
A 1 x 10 mL whole blood sample to assess vaccine-specific cytokine levels and in-vitro 
inhibition of tumor cell growth will be obtained from each patient at Days 0, 84 then every 
84 days and at EoT visit. When vaccination with IMU-131 occurs, these samples will be 
taken prior to vaccination. 
3) Phase 2 and Phase 2 Extension Immunologic Assessments
a) Humoral samples (Baseline, Days 21, 42, 63, 84, 126 then every 42 days and
EoT visit
A 1 x 10 mL whole blood sample for humoral immunity will be obtained from each patient 
at Days 0, 21, 42, 63, 84, 126 then every 42 days and at EoT visit. When vaccination with 
IMU-131 occurs, these samples will be taken prior to vaccination. 
b) Cellular samples (Screening [Phase 2 Extension only], Baseline, Days 84
then every 84 days and EoT visit)
Collection of 40 mL blood sample will be performed for PBMC isolation and analysis of 
cellular parameters at Days 0, 84 then every 84 days and at EoT visit. When vaccination 
with IMU-131 occurs, these samples will be taken prior to vaccination. 
During the Phase 2 Extension study, a Screening Visit collection of 40 mL blood sample 
for PBMC isolation and analysis of cellular parameters will be performed after enrolment 
eligibility including HER2 over-expression is confirmed. 


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8.7. 
Phase 2/Phase 2 Extension HER2/neu overexpression (Screening) 
Confirmation of HER2/neu overexpression is required for inclusion in this study. 
A previous pathology result confirming HER2/neu overexpression is acceptable. If analysis 
of a tumor biopsy is required for confirmation of HER2/neu overexpression, then this may 
be achieved via analysis of a fresh or archived tissue sample. 
HER2/neu analysis will be conducted at each center’s local pathology laboratory by 
immunohistochemistry (IHC) and fluorescent in situ hybridization [FISH], brightfield 
double in situ hybridization [BDISH], or chromogenic in situ hybridization [CISH] if IHC 
result is equivocal. 
Using the IHC method an unequivocal result of HER2 overexpression is defined as HER2 
+++, an equivocal result is defined as HER2 ++, and a negative result is defined as HER2 
+. If equivocal result (IHC HER2 ++) then additional analysis via FISH, BDISH or CISH 
will be conducted for confirmation of HER2 overexpression. The definition of FISH, 
BDISH or CISH positivity in gastric or gastro–esophageal junction cancer is a HER2: 
8.8. 
Phase 2/Phase 2 Extension ECOG performance grade (Screening, 
Baseline, Days 84 then every 84 days and EoT visit) 
The ECOG performance grade should be determined using the criteria defined in Appendix 
3: ECOG Performance Status Scale. 
8.9. 
Phase 2/Phase 2 Extension Pregnancy Test (at each study visit, 
excluding post- treatment follow-up visits) 
For female patients of childbearing potential, a urine pregnancy test, with sensitivity of at 
least 25 mIU/mL, will be performed immediately before administration of each vaccine 
dose. A negative pregnancy test result is required before the patient may receive the 
investigational product. If urine pregnancy test is positive, then confirmation of pregnancy 
will be by local laboratory BHCG blood test. If BHCG blood test is negative, then 
vaccination schedule may resume. 
8.10. Phase 2/Phase 2 Extension Intra-tumor analysis (Screening, Day 84 and 
post- progression) 
A screening visit or archival tumor biopsy sample will be obtained for all patients for intra- 
tumor analysis (unless HER2 status has been confirmed previously and archival tissue 
is not available). An optional Day 84 and optional post-progression tumor sample will be 
requested from patients. These samples will be analyzed for intra-tumor T cells and 
biochemical markers. The screening visit biopsy sample may also be used to determine 
HER2/neu overexpression. 
8.11. Phase 2/Phase 2 Extension Unscheduled Visit 
Unscheduled visits may be conducted at any time during Phase 2 by the investigator if 
clinically indicated for the care of the patient. 


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An unscheduled visit may include any of the protocol required assessments listed in Section 
8: Phase 2 Assessments. The exact assessments conducted at the unscheduled visit will be 
specified by the investigator and recorded in the CRF. Additional tests and procedures may 
be performed at the unscheduled visit for the clinical care of the patient after discussion 
with, and agreement of, the medical monitor. 
8.12. Phase 2 Post-treatment Follow Up (FU) Visit (Every 42 days after EoT 
visit) 
After disease progression, anti-cancer therapy and survival information will be collected 
every 6 weeks until death, withdrawal or end of trial. Anti-cancer therapy and survival 
information may be collected more frequently than every 6 weeks for quality control and 
data cleaning purposes. After discontinuation from the study for any reason other than 
disease progression, radiographic change will be collected every 6 weeks until 
determination of progressive disease. 
All patients will be followed for radiographic change until determination of progressive 
disease and survival information and anti-cancer treatment until death, unless the patient 
requests to be withdrawn from radiographic change assessment and survival follow-up 
contact or the trial ends. Requests for withdrawal must be documented in the source 
documents and signed by the investigator. 
Phase 2 extension patients will no longer complete Post-Treatment Follow Up visits. 
9.
ADVERSE EVENT REPORTING
9.1. 
Adverse Events 
All observed or volunteered AEs regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
sections. All AEs will be collected in response to a general question about the subject’s 
well-being and any possible changes from the baseline or previous visit, but shall not be 
specifically solicited with respect to particular AEs. 
For all AEs, the investigator must pursue and obtain information adequate both to 
determine the outcome of the AE and to assess whether it meets the criteria for 
classification as an SAE requiring immediate notification to Imugene Limited or its 
designated representative. For all AEs, sufficient information should be obtained by the 
investigator to determine the causality of the AE. The investigator is required to assess 
causality. AEs will be followed until resolved, stable, or until the subject’s last study visit 
or lost to follow-up. If an AE is not resolved or stabilized at the subject’s last visit, it is up 
to the discretion of the investigator and the Sponsor’s medical monitor to determine if 
further monitoring of the event is warranted. 
As part of ongoing safety reviews conducted by the Sponsor, any non-serious adverse event 
that is determined by the Sponsor to be serious will be reported by the Sponsor as an SAE. 
To assist in the determination of case seriousness further information may be requested 
from the investigator to provide clarity and understanding of the event in the context of the 
clinical trial. 


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9.2. 
Reporting Period 
For AEs/SAEs, the active reporting period to Imugene Limited or its designated 
representative begins from the time that the patient provides informed consent, which is 
obtained prior to the patient’s participation in the study, i.e., prior to undergoing any study- 
related procedure and/or receiving investigational product, through and including 28 
calendar days after the last administration of the investigational product, including 
administration during long term maintenance. After informed consent has been obtained 
but prior to initiation of study drug(s), only SAEs caused by a protocol-mandated 
intervention (e.g., invasive procedures such as biopsies, discontinuation of medications) 
should be reported. 
The cause of death must be reported as an SAE if it occurs at any time after the SAE 
reporting period and is likely to be related to the investigational product. 
9.3. 
Definition of an Adverse Event 
An AE is any untoward medical occurrence in a clinical investigation patient administered 
a product or medical device; the event need not necessarily have a causal relationship with 
the treatment or usage. Examples of AEs include but are not limited to: 
Abnormal test findings; 
Clinically significant symptoms and signs; 
Changes in physical examination findings; 
Hypersensitivity; 
Drug abuse; 
Drug dependency. 
Additionally, they may include the signs or symptoms resulting from: 
Drug overdose; 
Drug withdrawal; 
Drug misuse; 
Drug interactions; 
Extravasation; 
Exposure during pregnancy; 
Exposure via breastfeeding; 
Medication error; 
Worsening of signs and symptoms of the malignancy under study should be 
reported as AEs in the appropriate section of the CRF. Disease progression 
assessed by measurement of malignant lesions on radiographs or other methods 
should not be reported as AEs. 


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9.4. 
Abnormal Test Findings 
The criteria for determining whether an abnormal objective test finding should be reported 
as an AE are as follows: 
Test result is associated with accompanying symptoms, and/or 
Test result requires additional diagnostic testing or medical/surgical intervention, 
and/or 
Test result leads discontinuation from the study, significant additional 
concomitant drug treatment, or other therapy, and/or 
Test result is considered to be an AE by the investigator or Sponsor. 
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE. Any abnormal test result that is determined to be an error does not require 
reporting as an AE. 
9.5. 
Serious Adverse Events 
An SAE is any untoward medical occurrence at any dose that: 
Results in death (not due to disease progression); 
Is life-threatening (immediate risk of death); 
Requires inpatient hospitalization or prolongation of existing hospitalization; 
Results in persistent or significant disability/incapacity (substantial disruption of 
the ability to conduct normal life functions); 
Results in congenital anomaly/birth defect; 
Is determined to be an important medical event by the study investigator. 
Medical and scientific judgment is exercised in determining whether an event is an 
important medical event. An important medical event may not be immediately life- 
threatening and/or result in death or hospitalization. However, if it is determined that the 
event may jeopardize the patient or may require intervention to prevent one of the other AE 
outcomes, the important medical event should be reported as serious. 
Examples of such events are 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. 
9.5.1. 
Adverse Events of Special Interest 
Abnormal values in AST and/or ALT concurrent with abnormal elevations in total bilirubin 
that meet the criteria outlined below in the absence of other causes of liver injury are 
considered potential cases of drug-induced liver injury (potential Hy’s Law cases) and 
should always be considered important medical events. 
The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the patient’s individual baseline values and underlying conditions. Patients who 


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present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values: 
Patients with AST or ALT and total bilirubin baseline values within the normal 
range who subsequently present with AST or ALT 3 times the upper limit of 
normal (X ULN) concurrent with a total bilirubin 2 X ULN with no evidence of 
hemolysis and an alkaline phosphatase 2 X ULN or not available.
For patients with preexisting ALT OR AST OR total bilirubin values above the 
upper limit of normal, the following threshold values should be used in the 
definition mentioned above:
-
For patients with pre-existing AST or ALT baseline values above the normal
range: AST or ALT 
2 times the baseline values and 
3 X ULN, or 
8 X LLN (whichever is smaller). 
Concurrent with
-
For patients with pre-existing values of total bilirubin above the normal
range: Total bilirubin increased by one time the upper limit of normal or
times the lower limit of normal (whichever is smaller).
The patient should return to the investigational site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results. This evaluation should 
include laboratory tests, detailed history and physical assessment. For oncology studies, 
the possibility of hepatic neoplasia (primary or secondary) should be considered.  In 
addition to repeating AST and ALT, laboratory tests should include albumin, creatine 
kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, 
prothrombin time (PT)/INR, and alkaline phosphatase. A detailed history, including 
relevant information, such as review of ethanol, acetaminophen, recreational drug and 
supplement consumption, family history, occupational exposure, sexual history, travel 
history, history of contact with a jaundiced patient, surgery, blood transfusion, history of 
liver or allergic disease, and work exposure, should be collected. Further testing for acute 
hepatitis A, B, or C infection and liver imaging (eg, biliary tract) may be warranted. All 
cases confirmed on repeat testing as meeting the laboratory criteria defined above, with no 
other cause for LFT abnormalities identified at the time should be considered potential Hy’s 
Law cases irrespective of availability of all the results of the investigations performed to 
determine etiology of the abnormal LFTs. Such potential Hy’s Law cases should be 
reported as SAEs. 
9.6. 
Hospitalization 
AEs reported from studies associated with hospitalization or prolongations of 
hospitalization are considered serious. Any initial admission (even if less than 24 hours) 
to a healthcare facility meets these criteria. Admission also includes transfer within the 
hospital to an acute/intensive care unit (eg, from the psychiatric wing to a medical floor, 
medical floor to a coronary care unit, neurological floor to a tuberculosis unit). 
Hospitalization does not include the following: 
Rehabilitation facilities; 


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Hospice facilities; 
Respite care (eg, caregiver relief); 
Skilled nursing facilities; 
Nursing homes; 
Routine emergency room admissions; 
Same day surgeries (as outpatient/same day/ambulatory procedures). 
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
AE is not in itself an SAE. Examples include: 
Admission for treatment of a preexisting condition not associated with the development of 
a new AE or with a worsening of the preexisting condition (eg, for work-up of persistent 
pre-treatment lab abnormality); 
Social admission (eg, patient has no place to sleep); 
Administrative admission (eg, for yearly physical exam); 
Protocol-specified admission during a study (eg, for a procedure required by 
the study protocol); 
Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery); 
Hospitalization for observation without a medical AE; 
Pre-planned treatments or surgical procedures should be noted in the baseline 
documentation for the entire protocol and/or for the individual patient. 
Admission exclusively for the administration of blood products. 
Diagnostic and therapeutic non-invasive and invasive procedures, such as surgery, should 
not be reported as AEs. However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an AE. For example, an acute 
appendicitis that begins during the AE reporting period should be reported as the AE, and 
the resulting appendectomy should be recorded as treatment of the AE. 
9.7. 
Adverse Event Severity Assessment 
9.7.1. 
Local (injection site) Adverse Event Intensity: 
Intensity of the following local AEs should be assessed as described in the table below 
adapted from the FDA, Center for Biologics Evaluation and Research (CBER), Guidance 
for Industry: Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers 
Enrolled in Preventive Vaccinxe Clinical Trials dated September, 2007: 


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Table 4: 
Grading of Local Adverse Event Intensity 
Local 
Reaction to 
Injectable 
Product 
Absent 
(Grade 0) 
Mild  
(Grade 1) 
Moderate 
(Grade 2) 
Severe  
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Pain 
Absent 
Does not 
interfere with 
activity 
Repeated use of 
non- narcotic pain 
reliever > 24 
hours or interferes 
with activity 
Any use of 
narcotic pain 
reliever or 
prevents daily 
activity 
Emergency 
room (ER) visit 
or 
hospitalization 
Tenderness 
Absent 
Mild discomfort 
to touch 
Discomfort with 
movement 
Significant 
discomfort at 
rest 
ER visit or 
hospitalization 
Erythema/ 
Redness * 
Absent 
2.5 – 5 cm 
5.1 – 10 cm 
> 10 cm 
Necrosis or 
exfoliative 
dermatitis 
Induration/ 
Swelling** 
Absent 
2.5 – 5 cm and 
does not 
interfere with 
activity 
5.1 – 10 cm or 
interferes with 
activity 
> 10 cm or
prevents daily
activity
Necrosis 
* In addition to grading the measured local reaction at the greatest single diameter, the measurement
should be recorded as a continuous variable.
** Induration/Swelling should be evaluated and graded using the functional scale as well as the actual
measurement.
9.7.2. 
Other Adverse Event Intensity Grading 
Patients will be evaluated for safety if they have received any treatment. Adverse events 
and other symptoms will be graded according to National Cancer Institute’s Common 
Toxicity Criteria for Adverse Events version 4.03 (CTCAE v4.03) in Phase 1b and with 
version 5.0 (CTCAE v5.0) in Phase 2/Phase 2 Extension. 
Table 5: 
Common Toxicity Criteria for Adverse Events version 4.03 (CTCAE v4.03) 
and version 5.0 (CTCAE v5.0) Grading 
GRADE 
Clinical Description of Severity 
0 
No Change from Normal or Reference Range (This grade is not included in the 
Version 4.0 or 5.0 document but may be used in certain circumstances.) 
1 
MILD Adverse Event 
2 
MODERATE Adverse Event 
3 
SEVERE Adverse Event 
4 
LIFE-THREATENING OR DISABLING Adverse Event 
5 
DEATH RELATED TO Adverse Event 


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9.8. 
Causality Assessment 
The investigator’s assessment of causality must be provided for all AEs (serious and non- 
serious); the investigator must record the causal relationship in the CRF, as appropriate, 
and report such an assessment in accordance with the serious adverse reporting 
requirements if applicable. An investigator’s causality assessment is the determination of 
whether there exists a reasonable possibility that the investigational product caused or 
contributed to an AE; generally the facts (evidence) or arguments to suggest a causal 
relationship should be provided. If the investigator does not know whether the 
investigational product caused the event, then the event will be handled as “related to 
investigational product” for reporting purposes, as defined by the Sponsor (see Section 
9.12: Reporting Requirements). If the investigator's causality assessment is "unknown but 
not related to investigational product", this should be clearly documented on study records. 
In addition, if the investigator determines an SAE is associated with study procedures, the 
investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable. 
9.9. 
Pregnancy 
Patients who become pregnant during the study period and up to at least 28 days following 
chemotherapy or 180 days after the last dose of IMU-131 must not receive additional doses 
of IMU-131 but may continue other study procedures at the discretion of the investigator. 
Patients should be instructed to notify the investigator if it is determined after completion 
of the study that they or their partner (male patients) became pregnant either during the 
study or within 28 days following chemotherapy or 180 days after the last dose of IMU-
131. 
If a pregnancy occurs within 28 days following chemotherapy or 180 days after the last 
dose of IMU-131, the pregnancy should be followed to term, any premature terminations 
reported, and the health status of the mother and child including date of delivery and the 
child’s gender and weight should be reported to Imugene Limited after delivery. The 
mother may freely choose to terminate the pregnancy as her own decision. Neither the 
Sponsor nor investigators should influence this decision in any way. Similarly, neither the 
investigators nor Sponsor have the right to intervene or influence 
this decision and any ensuing procedures. If this occurs, the termination of pregnancy 
should be considered an elective surgical procedure and any associated adverse events 
attributed accordingly. 
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly 
[in a live born, a terminated fetus, an intrauterine fetal demise, or a neonatal death]), the 
investigator should follow the procedures for reporting SAEs. 


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9.10. Withdrawal Due to Adverse Events (See Also Section 6.5: Patient 
Withdrawal) 
Withdrawal due to AE should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted earlier, and recorded on the appropriate AE CRF 
page. 
When a patient withdraws due to an SAE, the SAE must be reported in accordance with 
the reporting requirements defined in Section 9.12. 
9.11. Eliciting Adverse Event Information 
The investigator is to report all directly observed AEs and all AEs spontaneously reported 
by the study patient. In addition, each study patient will be questioned about AEs. 
9.12. Reporting Requirements 
Each AE is to be assessed to determine if it meets the criteria for SAEs. If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate. 
9.12.1. 
Serious Adverse Event Reporting Requirements 
If an SAE occurs, Imugene Limited, or its delegated representative, is to be notified within 
24 hours of investigator awareness of the event. 
In particular, if the SAE is fatal or life-threatening, notification must be made immediately 
to Imugene Limited, or its delegated representative, irrespective of the extent of available 
AE information. This timeframe also applies to additional new information (follow-up) on 
previously forwarded SAE reports as well as to the initial and follow-up reporting of 
exposure during pregnancy and exposure via breastfeeding cases. 
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study patient initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his/her first awareness of the AE. 
For all SAEs, the investigator is obligated to pursue and provide information to Imugene 
Limited in accordance with the timeframes for reporting specified above. In addition, an 
investigator may be requested by Imugene Limited to obtain specific additional follow-up 
information in an expedited fashion. This information collected for SAEs is more detailed 
than that captured on the AE CRF. In general, this will include a description of the AE in 
sufficient detail to allow for a complete medical assessment of the case and independent 
determination of possible causality. Information on other possible causes of the event, such 
as concomitant medications and illnesses must be provided. In the case of a patient death, 
a summary of available autopsy findings must be submitted as soon as possible to Imugene 
Limited or its designated representative. 


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9.12.2. 
Non-Serious Adverse Event Reporting Requirements 
All AEs and SAEs that occur after the last informed consent date (i.e. in the case of re- 
screened patients) will be reported on the AE page(s) of the CRF. It should be noted 
that an additional form for collection of detailed SAE information will be provided. Where 
the same data are collected, the forms must be completed in a consistent manner. For 
example, the same AE term should be used on both forms. AEs should be reported using 
concise medical terminology on the CRFs as well as on the form for collection of SAE 
information. 
9.12.3. 
Sponsor Reporting Requirements to Regulatory Authorities 
Adverse event reporting, including suspected serious unexpected adverse reactions, will be 
carried out in accordance with applicable local regulations. 
10.
DATA ANALYSIS/STATISTICAL METHODS
10.1. Phase 1b Cohort Review Committee (CRC) 
Prior to enrollment of patients into the Phase 1b study, a CRC, comprising relevant site 
investigators, the Medical Monitor, and Sponsor representatives, will oversee safety, cohort 
evaluation and dose-escalation for the study. A formal charter which will establish the rules, 
meeting frequency and scope of responsibilities of the CRC will be established for the 
conduct of the CRC. 
After enrollment in Phase 1b begins the CRC will meet in person or by teleconference as 
soon as feasible after any of the following occur to determine if the criteria for dose limiting 
toxicity (DLT) has been met: 
One or more patients experience a serious adverse reaction assessed as related to 
the vaccine by the investigator 
One or more patients experience anaphylaxis 
Two or more patients in a single dose cohort experience an SAE explained by 
a diagnosis related to vaccination. (For grading of severity see CTCAE v4.03.) 
The CRC will review the safety data and make recommendations on the continuation of the 
study following the procedures outlined in the CRC charter. 
All decisions will be documented in the form of minutes. 
10.1.1. 
Phase 1b Definition of Dose-Limiting Toxicity (DLT) 
A dose limiting toxicity (DLT) is defined as a drug-related Grade 3 toxicity that cannot be 
resolved to a Grade 1 with appropriate therapy within 2 weeks, or a Grade 4 or greater 
toxicity graded by CTCAE v4.03, related to the IMU-131 vaccine. 


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10.1.2. 
Phase 1b Dose Escalation 
There will be up to 6 patients in each cohort in Phase 1b. The CRC will review data from 
one complete cycle of chemotherapy (including 3 doses of IMU-131, on Days 0, 14, and 
35) for at least 3 patients in a dose cohort to authorize dose escalation.
A staggered enrollment will be used for patient safety, whereby a dose cohort must be 
completed and reviewed by the CRC before further recruitment. The decision whether to 
escalate to the next dose cohort will be made by the CRC when at least 3 patients in the 
current dose cohort have completed chemotherapy cycle 1 (35 days of the study, including 
3 doses of IMU-131 on Days 0,14 and 35). 
Phase 1b dose escalation will involve 3 dose levels of IMU-131 with a standard 3+3 scheme 
for determination of safety prior to dose escalation. Patients will receive 3 doses of IMU-
131 (Days 0, 14 and 35) with chemotherapy being initiated 14 days after the first dose of 
IMU-131 with evaluation occurring after the first 21-day cycle of chemotherapy and before 
opening the enrollment to the next higher dose cohort. 
Dose Escalation Decision Rules 
If 0 out of 3 patients with treatment DLT at a given IMU-131 dose level, enter 
3 patients at the next dose level;
If 
 3 patients with treatment related DLT at a given dose level, dose escalation 
will be stopped. This dose level will be declared the maximally administered dose 
(highest dose administered). Three (3) additional patients will be entered at the 
next lower dose level if only 3 patients were treated previously at that dose;
If 1 out of 3 patients with treatment related DLT at a given dose level, enter at 
least 3 more patients at this dose level. If 0 of these 3 patients experience treatment 
related DLT, proceed to the next dose level. If 1 or more of this group suffer 
treatment related DLT, then dose escalation is stopped, and this dose is declared 
the maximally administered dose. Three (3) additional patients may be entered at 
a dose between the current dose and the next lowest dose level, the exact dose of 
which will be determined by the CRC.
10.2. Phase 1b Analysis 
Demographic data of for the study group will be tabulated. 
Safety data: 
Listings will be made of the safety data collected at each time point. 
 
 
 
 


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Immunogenicity data: 
Immunological data for each time point will be analyzed. 
Radiographic data: 
Radiographic data for each time point will be analyzed. 
10.2.1. 
Phase 1b Efficacy Analysis 
The dose effect of IMU-131 will be evaluated in Phase 1b by immunogenicity data: P467- 
specific antibodies (IgG) and Her-2- specific antibodies (IgG) titers. Additionally, 
vaccine-specific cytokine responses will be evaluated before and 21 days after the third 
vaccine dose. 
10.2.2. 
Phase 1b Safety Analysis 
The statistical considerations for this study are defined in a detailed Statistical Analysis 
Plan (SAP). This section focuses on the statistical considerations for the primary objectives. 
This study and therefore the statistical considerations will be overseen and governed by the 
CRC and the CRC charter. 
The conjecture for Phase 1b is that the cohort receiving the 50 µg dose will have a higher 
HER2/neu antibody titer than the cohort receiving a lower dose at the assessment time 
points and that the IMU-131-associated AEs at the 50 µg dose will be acceptable for 
adoption as recommended phase 2 dose in Phase 2. The study has minimal statistical power 
for a statistical test ascertaining this conjecture and it will be done descriptively. 
10.2.3. 
Phase 1b Interim Analysis 


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10.3. Phase 2 Independent Data Monitoring Committee (IDMC) 
During Phase 2, an IDMC, comprising independent physicians, an independent statistician, 
the medical monitor, and Sponsor representatives, will monitor data from the study. The 
medical monitor and Sponsor representatives will only participate in open sessions at 
IMDC meetings. The IDMC will be scheduled to meet after 8, 16 and 24 progression events 
occur and at intervals no less than once per year. Further details of the IDMC meetings and 
review procedures will be contained in the IDMC charter. A formal charter which will 
establish the rules, meeting frequency and scope of responsibilities of the IDMC will be 
established for the conduct of the IDMC. 
10.4. Phase 2 Analysis 
10.4.1. 
Phase 2 Analysis Populations 
The Intent-to-Treat (ITT) population: All randomized patients. The primary 
efficacy analysis will be based on this population. ITT analyses will be conducted 
on the basis of the randomized treatment.
The Evaluable Set (EVAL): All randomized patients who receive any amount of 
study treatment and have at least 1 evaluable post-baseline tumor response. EVAL 
analyses will be conducted on the basis of the randomized treatment.
The Full Analysis Set (FAS): All randomized patients who receive any amount of 
study treatment. FAS analyses will be conducted on the basis of the randomized 
treatment.
Safety population: All randomized patients who receive any amount of study 
treatment. All safety analyses will be based on this population. The safety 
population will be conducted on the basis of the actual treatment received.
A Per-Protocol (PP) subset may also be used to analyze select efficacy endpoints 
and will be based on study drug exposure (compliance and/or time on study drug) 
and major protocol deviations. The criteria for inclusion in the PP subset will be 
finalized and documented prior to data base lock.
10.4.2. 
Phase 2 Efficacy Analysis 
 
 
 
 
 
 
 
 
 
 
 
 


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Analysis of the primary endpoint, OS, and secondary endpoint, PFS, will be performed 
using the ITT population. Additional secondary and exploratory analyses of efficacy 
endpoints will be performed using the ITT, FAS, and/or the EVAL sets. Ancillary analyses 
of select efficacy endpoints may also be performed using the PP set. 
The log-rank method will be used to estimate the secondary efficacy parameter of PFS. 
Analyses of TTP, DCR, ORR, DOR and CTS will be performed using the same methods 
as described for PFS. The blinded central review disease response assessments will be used 
as the primary measure for these analyses, and the Investigator disease response 
assessments will be used as supportive measures for these analyses. 
Patients who are continuing in the study at the time of the primary final analysis will 
continue to be followed per the schedule of assessments until completion of the study; a 
supplementary analysis may be produced to reflect any additional data collected after the 
primary final analysis. 
10.4.3. 
Phase 2 Safety Analysis 
All safety analyses will be conducted in the safety population. 
AEs will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA), version 21.0, or higher. The severity of AEs will be graded according to NCI 
CTCAE, version 5.0. 
Treatment-emergent adverse events (TEAEs) are defined as any AE occurring or worsening 
on or after the first study drug dose and within 30 days after the last dose date. TEAEs, 
TEAEs 
leading 
to 
study 
drug 
discontinuation, 
TEAEs 
leading 
to 
dose 
reduction/interruption, TEAEs related to study drug, SAEs, and TEAEs with an outcome 
of death will be summarized by system organ class, and preferred term for each treatment 
group. A summary of TEAEs of NCI CTCAE Grade 3 or higher, as well as the most 
frequent TEAEs (preferred terms), and TEAEs by relationship to study treatment, will be 
provided. AE incidence rates will also be summarized adjusting for duration of study 
treatment. 
Values and changes from baseline in clinical laboratory results will be summarized by visit. 
Clinical laboratory values will be graded according to NCI CTCAE 5.0, for applicable tests. 
Shifts in toxicity grades from baseline grade will be summarized. 
Vital signs, ECG, and concomitant medication data will be summarized. Graphical displays 
will be provided where useful to assist in the interpretation of results. 
10.5. Phase 2 Dose Escalation Cohort Review Committee (CRC) 
During the Phase 2 dose escalation study, a CRC, comprising relevant site investigators, 
the Medical Monitor, and Sponsor representatives, will oversee safety, cohort evaluation 
and dose-escalation for the study. A formal charter which will establish the rules, meeting 
frequency and scope of responsibilities of the CRC will be established for the conduct of 
the CRC. 


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Toxicity data for each cohort will be reviewed prior to dose escalation approval by CRC. 
Each CRC meeting will be held after each dose cohort has completed Day 35 and prior to 
initiation of the next dose cohort. The CRC will review the complete, pre-defined safety 
dataset from each dose cohort and will determine, with advice from the Medical Monitor, 
the appropriate dose limiting toxicity (DLT) rule (see Section 10.5.1 Definition of Dose- 
Limiting Toxicity and Section 10.5.2 Dose Escalation Decision Rules, for details) and 
whether the study will proceed to the next dose cohort. A dose cohort must have 
completed Day 35 of the study, including 3 doses of IMU-131 and 1 cycle of chemotherapy 
prior to the CRC meeting and opening of the next higher dose cohort for enrollment. All 
DLTs will be reviewed by CRC irrespective of whether patients receive 1, 2, or 3 doses of 
IMU-131 during the DLT assessment period. 
The CRC will review all available safety/tolerability and immunogenicity data and make 
recommendations regarding dose escalation and the continuation of the study following the 
procedures outlined in the CRC charter. 
All decisions will be documented in the form of minutes. 
10.5.1. 
Phase 2 Dose Escalation Definition of Dose-Limiting Toxicity (DLT) 
A dose limiting toxicity (DLT) is defined as an IMU-131-related Grade 3 toxicity that 
cannot be resolved to a Grade 1 with appropriate therapy within 2 weeks, or a Grade 4 or 
greater toxicity graded by CTCAE v5.0, related to the IMU-131 vaccine. 
In addition, after enrollment in Phase 2 dose escalation begins, the CRC will meet by 
teleconference as soon as feasible after any of the following occur to determine if the 
criteria for dose limiting toxicity (DLT) has been met: 
One or more patients experience a serious adverse reaction assessed as related to 
the vaccine by the investigator.
One or more patients experience anaphylaxis.
10.5.2. 
Phase 2 Dose Escalation 
Between 3 - 6 patients will be enrolled in each Phase 2 dose escalation cohort for safety 
evaluation by CRC prior to next dose being opened to enrollment. The CRC will review 
data from one complete cycle of chemotherapy and 3 doses of IMU-131, for at least 
3 patients in a dose cohort to authorize dose escalation. The DLT window is 35 days. 
-131, within a standard 3 + 3 scheme for
-131 dose cohort. A
dose cohort must be reviewed by CRC for DLTs according to dose escalation decision rules 
before opening the next dosed cohort. 
Either 
CRC clearance of the 35-day DLT period. 


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Phase 2 Dose Escalation Decision Rules: 
If 0 out of 3 patients with treatment DLT at a given IMU-131 dose level, enter 
3 patients at the next dose level;
If 
 3 patients with treatment related DLT at a given dose level, dose escalation 
will be stopped. This dose level will be declared the maximally administered dose 
(highest dose administered). Three (3) additional patients will be entered at the 
next lower dose level if only 3 patients were treated previously at that dose;
If 1 out of 3 patients with treatment related DLT at a given dose level, enter at 
least 3 more patients at this dose level. If 0 of these 3 patients experience treatment 
related DLT, proceed to the next dose level. If 1 or more of this group suffer 
treatment related DLT, then dose escalation is stopped, and this dose is declared 
the maximally administered dose. Three (3) additional patients may be entered at 
a dose between the current dose and the next lowest dose level, the exact dose of 
which will be determined by the CRC.
10.6. Phase 2 Extension Analysis 
Dose escalation cohorts will be analyzed and reported when all patients have completed 
Day 42 RECIST assessment or End of Trial. 
Demographic data for the study group will be tabulated. 
AEs will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA), version 21.0, or higher. The severity of AEs will be graded according to NCI 
CTCAE, version 5.0. 
Treatment-emergent adverse events (TEAEs) are defined as any AE occurring or worsening 
on or after the first study drug dose and within 30 days after the last dose date. TEAEs, 
TEAEs 
leading 
to 
study 
drug 
discontinuation, 
TEAEs 
leading 
to 
dose 
reduction/interruption, TEAEs related to study drug, SAEs, and TEAEs with an outcome 
of death will be summarized by system organ class, and preferred term for each treatment 
group. A summary of TEAEs of NCI CTCAE Grade 3 or higher, as well as the most 
frequent TEAEs (preferred terms), and TEAEs by relationship to study treatment, will be 
provided. AE incidence rates will also be summarized adjusting for duration of study 
treatment. 
Values and changes from baseline in clinical laboratory results will be summarized by visit. 
Clinical laboratory values will be graded according to NCI CTCAE 5.0, for applicable tests. 
Shifts in toxicity grades from baseline grade will be summarized. 
Vital signs, ECG, and concomitant medication data will be summarized. Graphical displays 
will be provided where useful to assist in the interpretation of results. 


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Immunogenicity data: 
Immunological data for each time point will be analyzed. 
Radiographic data: 
Radiographic data for each time point will be analyzed. 
Survival data: 
Overall survival data for each patient will be analyzed. 
10.6.1. 
Phase 2 Dose Escalation Safety Analysis 
The statistical considerations for this study are defined in a detailed Statistical Analysis 
Plan (SAP). This section focuses on the statistical considerations for the primary objectives. 
The Phase 2 dose escalation study, and therefore the statistical considerations, will be 
overseen and governed by the CRC and the CRC charter. 
 
 
10.6.2. 
Phase 2 Dose Escalation Interim Analysis 
No formal interim analysis of the Phase 2 dose escalation study is planned. Analysis 
will be conducted separately for each dose cohort after all patients in each dose escalation 
and expansion cohort have completed Day 42. 
 
 
10.6.3. 
Phase 2/Phase 2 Extension General Considerations 
Summaries will be performed by treatment and overall. 
 
 
 
 
 
 
 
 


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10.7. Sample Size Determination 
10.7.1. 
Phase 1b Sample Size Determination 
 
 
 
 
 
10.7.2. 
Phase 2 Sample Size Determination 


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PFS will be assessed as a secondary outcome with an analysis following 24 evaluable 
progression events coded using RESIST 1.1 with patients not having a progression being 
censored at the time of last evaluation for progression or counted as a progression event if 
death is within 42 days of last evaluation for progression. 
Assumptions of accrual time, loss to follow-up, and pooled event rate (both arms 
combined) used in the sample size calculations may be monitored. The number of patients 
enrolled, and duration of enrolment and follow-up may be adjusted to achieve the planned 
number of events at the time of the final analysis of the primary endpoint. 
10.7.3. 
Phase 2 Extension Sample Size Determination 
Phase 2 dose escalation will enroll up to 20 patients. No formal statistical calculation of 
sample size will be used for the Phase 2 dose escalation. The sample size is empirical and 
based on a standard 3+3 dose escalation design with expansion of up to 10 patients per 
cohort. 
11.
DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record 
As used in this protocol, the term CRF should be understood to refer to either a paper form 
or an electronic data record or both, depending on the data collection method used in this 
study. 
A CRF is required and should be completed for each included patient. The completed 
original CRFs are the sole property of Imugene Limited and should not be made available 
in any form to third parties, except for authorized representatives of Imugene Limited or 
appropriate regulatory authorities, without written permission from Imugene Limited. 
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic / original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring and available when required. The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs is true. Any corrections to entries made in the CRFs, source 
documents must be dated, initialed and explained (if necessary) and should not obscure the 
original entry. 
In most cases, the source documents are the hospital's or the physician's patient chart. 
In these cases data collected on the CRFs must match the data in those charts. 
11.2. Record Retention 
Essential documents such as protocols, amendments, IRB/IEC approvals, signed ICFs, 
source documents, CRFs, drug accountability records should be retained until at least 
are no pending or contemplated marketing applications in an ICH region, or until at least 
drug. These documents should be retained for a longer period, if required by the applicable 


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regulatory requirements or by an agreement with the Sponsor. It is the responsibility of the 
Sponsor to inform the Investigator or Sub-Investigator and/or institution as to when these 
documents no longer need to be retained. 
The investigator must obtain Imugene Limited's written permission before disposing of any 
records, even if retention requirements have been met. 
12.
ETHICS
12.1. Institutional Review Board (IRB)/Independent Ethics Committee 
(IEC) 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, eg, 
recruitment advertisements, if applicable, from the IRB/IEC. All correspondence with the 
IRB/IEC should be retained in the Investigator File. Copies of IRB/IEC approvals should 
be forwarded to Imugene Limited, or its agent. 
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval 
is where the change is necessary to eliminate apparent immediate hazards to the patients. 
In that event, the investigator must notify the IRB/IEC and Imugene Limited in writing 
immediately after the implementation. 
12.2. Ethical Conduct of the Study 
The study will be conducted in accordance with legal and regulatory requirements, as well 
as the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
Sciences 2002), Guidelines for GCP (ICH 1996), and the Declaration of Helsinki (World 
Medical Association 1996, 2008). 
In addition, the study will be conducted in accordance with the protocol, the ICH guideline 
on GCP, and applicable local regulatory requirements and laws. 
12.3. Patient Information and Consent 
All parties will ensure protection of patient personal data and will not include patient names 
on any Sponsor forms, reports, publications, or in any other disclosures, except where 
required by laws. 
Patient names, address, birth date and other identifiable data will be replaced by a numerical 
code consisting of a numbering system provided by Imugene Limited, or its delegate, in 
order to de-identify the trial patient. In case of data transfer, Imugene Limited and its agents 
will maintain high standards of confidentiality and protection of patient personal data. 
The informed consent document must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements. 


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The informed consent document used in this study, and any changes made during the course 
of the study, must be prospectively approved by both the IRB/IEC and Imugene Limited, 
or its agent, before use. 
The investigator must ensure that each study patient, or his/her legal representative, is fully 
informed about the nature and objectives of the study and possible risks associated with 
participation. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each patient or the patient's legal representative before any study-specific 
activity is performed. The investigator will retain the original of each patient's signed 
consent document. 
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP 
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
Competent Authority in any area of the World, or if the investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of the 
investigational product, Imugene Limited should be informed immediately. 
In addition, the investigator will inform Imugene Limited immediately of any urgent safety 
measures taken by the investigator to protect the study patients against any immediate 
hazard, and of any serious breaches of this protocol or of ICH GCP that the investigator 
becomes aware of. 
13.
STUDY CONDUCT CONSIDERATIONS
13.1. Protocol and Investigator’s Brochure (IB) 
All study personal must be familiar with the protocol to be able to conduct the study in the 
manner specified. 
Imugene Limited has supplied the investigator with an Investigator’s Brochure (IB), which 
describes the vaccine being tested and its known adverse effects. The investigator must be 
familiar with this document before the study commences. Imugene Limited will provide 
additional information requested by the investigator before commencing the study or 
during its conduct. 
This protocol cannot be altered or changed except through a formal protocol amendment, 
which requires the written approval of Imugene Limited. The protocol amendment must be 
signed by the investigator and approved by the IRB or IEC before it may be implemented. 
Protocol amendments will be filed with the appropriate regulatory agencies having 
jurisdiction over the conduct of the study. 
13.2. Confidentiality 
Either prior to or during the course of the study, Imugene Limited or their representatives 
will provide the principal investigator and persons delegated by him/her with confidential 
information, for example, but not limited to, the protocol and the IB. The information may 


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not be disclosed to anyone else without prior approval from Imugene Limited in writing. 
This obligation of confidentiality shall survive the completion or early termination of the 
study. 
13.3. Documentation and Material Supplies 
All supplies provided to the investigators for the purpose of carrying out the study are 
supplied only for the purpose of the study and must not be used for any other purpose. The 
principal investigator or (a) person(s) delegated by the principal investigator is/are 
responsible for the security and accountability of all supplies. All such supplies, if not used 
during the course of the study and not forming a part of the documentation required to be 
retained by the investigator, must be returned to Imugene Limited at the conclusion of the 
study. 
13.4. Monitoring 
The study will be monitored by a CRO. Its representatives will be allowed access to all 
information resulting from this study and Imugene Limited will have an unrestricted right 
to use such information. The study monitor will have access to laboratory test reports and 
other patient records needed to verify the entries on the CRF. The patients’ confidentiality 
will be respected as required by local law. 
13.5. Quality Assurance Audit 
This study may be audited by Imugene Limited or its designee to document the authenticity 
of recorded data and protocol adherence. Patients participating in the study should be 
informed that their records might be reviewed for this purpose, and also by government 
health authorities. The patients’ confidentiality will be respected as required by local law. 
13.6. Compensation for Medicine-induced Injury 
According to local regulations Imugene Limited will provide insurance coverage to all 
patients during study period. Imugene Limited assumes liability for and will indemnify all 
injuries that occur to patients whenever a causal relationship can be established between 
the event and the clinical trial procedure or the trial substance under study if the following 
can be demonstrated: 
The event resulted from a trial substance, provided that the substance was 
administered according to the current protocol and manufacturer’s instructions. 
The event occurred as a consequence of diagnostic procedures performed 
according to the trial protocol. 
The event resulted from therapeutic or diagnostic measures legitimately required 
as a consequence of unexpected events caused by the trial substance, by 
comparative medication, or by diagnostic procedures called for by the trial 
protocol. 
Imugene Limited is not liable for events that occur solely as a consequence of the 
underlying illness of the patient, or for events resulting from diagnostic or therapeutic 
measures not specifically required by the protocol, or for events resulting from negligence 


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(including failure to act according to accepted medical practice, or to comply strictly with 
the protocol or the terms of this Agreement) of the investigator or any other involved and/or 
related clinical staff and facilities. 
This indemnity provided by Imugene Limited shall further apply as follows: 
Imugene Limited is to be informed as soon as possible of any complaint, action or suit of 
proceeding giving rise to the right of indemnification, and the investigator agrees to co- 
operate fully with Imugene Limited in the defense or disposition of all such cases. 
Imugene Limited will be permitted, at its costs and discretion, to handle and control the 
defense or disposition of all such cases. 
No case will be settled without the prior written consent of Imugene Limited. 
14.
DEFINITION OF END OF TRIAL
End of trial is defined as 28 days post the last patient completing the end of treatment visit. 
15.
SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, drug safety problems, or at the discretion of Imugene. 
In addition, Imugene retains the right to discontinue development of IMU-131 at any time. 
If a study is prematurely terminated or discontinued, Imugene will promptly notify the 
investigator. After notification, the investigator must contact all participating patients and 
the hospital pharmacy (if applicable) within 7 days. As directed by Imugene, all study 
materials must be collected and all CRFs completed to the greatest extent possible. 
16.
PUBLICATION OF DATA AND PROTECTION OF TRADE
SECRETS
In accordance with standard editorial and ethical practice, Imugene Limited will support 
publication of multicenter trials only in their entirety and not as individual center data 
except for data on substudies. 
The following rules will apply for determining authorship: 
Authorship credit will be based on the Vancouver statement by the International Committee 
of Medical Journal Editors, i.e. substantial contribution to the following criteria: 
i)
Conception and design or analysis and interpretation;
ii)
Drafting article or critically revising it for intellectual content;
iii)
Final approval of the version to be published;
Additional criteria for authorship include: 
iv)
Contributors who register 20% or more of the evaluable cases on the study;
v)
Significant contribution to the Cohort Review Committee.


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In an appropriate footnote, or at the end of the article, the following statement will be made: 
“Participating investigators included: (a list of the individuals who have 
contributed patients and their institutions).” 
Investigator agrees to submit all manuscripts or abstracts to Imugene Limited prior to 
submission. This allows Imugene Limited to protect proprietary information and to provide 
comments based on information from other studies that may not yet be available to the 
authors of the manuscript. Investigator will collaborate with the study statistician for 
preparation of trial data analyses intended to be used in the publication(s) of the study. 
Any formal publication of the study in which input of Imugene Limited personnel exceeded 
that of conventional monitoring will be considered as a joint publication by Investigator 
and Imugene Limited. 
Moreover, the following points need to be considered: 
Without Investigator’s prior written consent, Imugene Limited may not make 
reference, either directly or indirectly, in a commercial publication, to 
Investigator’s name or institution, or any of its employees in which Investigator 
performed the present trials, connected with the research and its results. 
Imugene Limited may not use Investigator’s name or the name of the 
 
 or its employees connected to the research or to the institution 
in which Investigator performed the present trial in its commercial publications as 
recommendation of quality and/or of the finished product and/or of the drug and 
the efficacy of its use. 
Should Imugene Limited decide to publish the research results, it must publish 
them in their entirety and must not quote anything out of context. 
Nothing in the aforementioned limitations in clauses will prevent Imugene Limited from 
quoting from articles, provided that the scientific source of data (scientific conventions, 
scientific newspapers) is mentioned. 


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17.
REFERENCES
Alanji AJ, et al. An open-label, multinational, multicenter study of G17DT vaccination 
combined with cisplatin and 5-fluorouracil in patients with untreated, advanced gastric or 
gastroesophageal cancer: the GC4 study. Cancer. 2006;106(9):1908-16. 
American Cancer Society. Survival rates for stomach cancer, by stage. Available 
at 
http://www.cancer.org/cancer/stomachcancer/detailedguide/stomach-cancer-survival-
rates. Accessed 28 August 2014. 
Coussens L, et al. Tyrosine kinase receptor with extensive homology to EGF receptor 
shares chromosomal location with neu oncogene. Science. 1985;230(4730):1132-9. 
Florea, A.M. and Büsselberg, D., 2011. Cisplatin as an anti-tumor drug: cellular 
mechanisms of activity, drug resistance and induced side effects. Cancers, 3(1), pp.1351- 
1371. 
Foon KA, et al. Clinical and immune responses in resected colon cancer patients treated 
with anti-idiotype monoclonal antibody vaccine that mimics the carcinoembryonic antigen. 
J Clin Oncol. 1999;17:2889-95. 
Giese, M., 2016. Introduction to Molecular Vaccinology. Springer. 
Gonzalez, G., Crombet, T., Torres, F., Catala, M., Alfonso, L., Osorio, M., Neninger, E., 
Garcia, B., Mulet, A., Perez, R. and Lage, R., 2003. Epidermal growth factor-based cancer 
vaccine for non-small-cell lung cancer therapy. Annals of Oncology, 14(3), pp.461-466. 
Haining, W.N., Neuberg, D.S., Keczkemethy, H.L., Evans, J.W., Rivoli, S., Gelman, R., 
Rosenblatt, H.M., Shearer, W.T., Guenaga, J., Douek, D.C. and Silverman, L.B., 2005. 
Antigen-specific T-cell memory is preserved in children treated for acute lymphoblastic 
leukemia. Blood, 106(5), pp.1749-1754. 
Hofmann M, et al. Assessment of a HER2 scoring system for gastric cancer: results from a 
validation study. Histopathology. 2008;52(7):797-805. 
International Agency for Research on Cancer (IARC). GLOBOCAN cancer fact sheets: 
stomach cancers. Available at http://globocan.iarc.fr/old/FactSheets/cancers/stomach- 
new.asp. Accessed 28 August 2014. 
Kim, Y.H., 2005. Chemotherapy for advanced gastric cancer: slow but further progress. 
Cancer Research and Treatment, 37(2), pp.79-86. 
Kim, R., Nishimoto, N., Inoue, H., Yoshida, K. and Toge, T., 2000. An analysis of the 
therapeutic efficacy of protracted infusion of low-dose 5-fluorouracil and cisplatin in 
advanced gastric cancer. Journal of Infection and Chemotherapy, 6(4), pp.222-228. 
Kim, N.K., Park, Y.S., Due Seog Heo, M.D., Jin, H. and Kim, M.D., 1993. A Phase 111 
Randomized Study of 5-Fluorouracil and Cisplatin Versus 5-Fluorouracil, Doxorubicin, 
and Mitomycin C Versus 5-Fluorouracil Alone in the Treatment of Advanced Gastric 
Cancer. Cancer, 71(12), pp.3813 – 3818. 


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Laws, H.J., Calaminus, G. and Göbel, U., 2005. Assessment of humoral immunity to 
poliomyelitis, tetanus, hepatitis B, measles, rubella, and mumps in children after 
chemotherapy. Cancer, 103(8), pp.1759-1759. 
Leong, T., 2005. Chemotherapy and radiotherapy in the management of gastric 
cancer. Current opinion in gastroenterology, 21(6), pp.673-678. 
Matsushita N, et al. Phase I clinical trial of a peptide vaccine combined with tegafur-uracil 
plus leucovorin for treatment of advanced or recurrent colorectal cancer. Oncol Rep. 
2013;29(3):951-9. 
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in 
Oncology 
– 
Gastric 
Cancer 
Version 
2.2017. 
Available 
at 
https://www.nccn.org/professionals/physician_gls/PDF/gastric.pdf 
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in 
Oncology 
– 
Gastric 
Cancer 
Version 
2.2018. 
Available 
at 
https://www.nccn.org/professionals/physician_gls/PDF/gastric.pdf 
Neninger, E., Verdecia, B.G., Crombet, T., Viada, C., Pereda, S., Leonard, I., Mazorra, Z., 
Fleites, G., Gonzalez, M., Wilkinson, B. and Gonzalez, G., 2009. Combining an EGF-based 
cancer vaccine with chemotherapy in advanced nonsmall cell lung cancer. Journal of 
Immunotherapy, 32(1), pp.92-99. 
NICE, National Institute for Health and Clinical Excellence: Trastuzumab for the treatment 
of HER2-positive metastatic gastric cancer 2010. TA208 (November). 
Ozkan, K., Turkkan, E., Ender, K., Mutlu, D., Murat, A., Nalan, B., Abdülmecit, Y. and 
Osman, M., 2005. 5-Fluorouracil, epirubicin and cisplatin in the treatment of metastatic 
gastric carcinoma: a retrospective analysis of 68 patients. Indian Journal of cancer, 42(2), 
p.85.
Park DI, et al. HER-2/neu amplification is an independent prognostic factor in gastric 
cancer. Dig Dis Sci. 2006;51(8):1371-9. 
Rexer BN, Arteaga CL. Intrinsic and acquired resistance to HER2-targeted therapies in 
HER2 gene-amplified breast cancer: mechanisms and clinical implications. Crit Rev 
Oncog. 2012;17(1):1-16. doi:10.1615/critrevoncog.v17.i1.20 
Rodríguez, P.C., Rodríguez, G., González, G. and Lage, A., 2010. Clinical development 
and perspectives of CIMAvax EGF, Cuban vaccine for non-small-cell lung cancer 
therapy. MEDICC Rev, 12(1), pp.17-23. 
Roy V, Perez EA. Beyond trastuzumab: small molecule tyrosine kinase inhibitors in HER- 
2-positive breast cancer. Oncologist. 2009;14(11):1061-9.
Santin AD, et al. Trastuzumab treatment in patients with advanced or recurrent endometrial 
carcinoma overexpressing HER2/neu. Int J Gynaecol Obstet. 2008;102(2):128-31. 
Siegel, Rebecca L., Kimberly D. Miller, and Ahmedin Jemal. "Cancer statistics, 2016." 
CA: a cancer journal for clinicians 66.1 (2016): 7-30. 


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Shiroiwa T, Fukuda T, Shimozuma K. Cost-effectiveness analysis of trastuzumab to treat 
HER2-positive advanced gastric cancer based on the randomised ToGA trial. Br J Cancer, 
2011;105(9):1273-8. 
Tan M, Yu D. Molecular mechanisms of erbB2-mediated breast cancer chemoresistance. 
Adv Exp Med Biol. 2007;608:119-129. 
Wagner S, et al. Delayed tumor onset and reduced tumor growth progression after 
gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin 
immunization with a Her-2/neu multi-peptide vaccine and IL-12 in c-neu transgenic mice. 
Breast Cancer Res Treat. 2007;106(1):29-38. 
Weir G, Liwski R, Mansour M. Immune Modulation by Chemotherapy or Immunotherapy 
to Enhance Cancer Vaccines. Cancers 2011;3: 3114-3142 
Wiedermann U, et al. A virosomal formulated Her-2/neu multi-peptide vaccine induces 
Her-2/neu-specific immune responses in patients with metastatic breast cancer: a phase I 
study. Breast Cancer Res Treat. 2010;119(3):673-83. 
Wiedermann, U., et al. (2021). Clinical and Immunologic Responses to a B-Cell Epitope 
Vaccine in Patients with HER2/neu-Overexpressing Advanced Gastric Cancer—Results 
from Phase Ib Trial IMU.ACS.001." Clinical Cancer Research 27(13): 3649-3660. 
Wiedermann, U., Sitte, H.H., Burgmann, H., Eser, A., Falb, P., Holzmann, H., Kitchen, M., 
Köller, M., Kollaritsch, H., Kundi, M. and Lassmann, H., 2016.[Guidelines for vaccination 
of immunocompromised individuals]. Wiener klinische Wochenschrift, 128(4), pp.337-
376. 
Yano T, et al. Comparison of HER2 gene amplification assessed by fluorescence in situ 
hybridization and HER2 protein expression assessed by immunohistochemistry in gastric 
cancer. Oncol Rep. 2006;15(1): p. 65-71. 
Zhang XL, et al. Comparative study on overexpression of HER2/neu and HER3 in gastric 
cancer. World J Surg. 2009;33(10):2112-8. 


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APPENDIX 1: FLOW DIAGRAM OF PHASE 1B
Allocation
Enrolment
Phase 1 data analysis
Study Completion
Dose Period 1:
Day 0 Vaccination, Day 2 Follow-up observations
Allocate to treatment (Day 0)
Screening Visit 
Assessment
Exclusion from study due to:
Not meeting inclusion
/exclusion criteria
Declined to participate
Other reasons
Participant recruitment and 
informed consent 
Dose Period 2:
Day 14 Vaccination, Day 16 Follow-up observations 
Begin 1st 21-day cycle of chemotherapy 
Dose Period 3:
Day 35 Vaccination, Day 37 Follow-up observations 
Begin 2nd 21-day cycle of chemotherapy 
Chemotherapy only Visit Day 77
Begin 4th 21-day cycle of chemotherapy
End of Treatment Visit Day 56 
Complete end of treatment procedures 
Begin 3rd 21-day cycle of chemotherapy 
Start of Long Term Maintenance Day 98
Start booster vaccination schedule 
Continue chemotherapy as clinically indicated


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APPENDIX 2: VACCINE – MONTANIDE EMULSION 
PREPARATION INSTRUCTIONS 
The vaccine – montanide emulsion preparation instructions can be found in the pharmacy 
manual. 


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APPENDIX 3: ECOG PERFORMANCE GRADE SCALE 
Grade 
Description 
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 or office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities.  Up 
and about 
 50% of waking hours 
3 
Capable of only limited self-care, confined to a bed or chair 
 50% of waking hours 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or chair 
5 
Dead 


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APPENDIX 4: THAILAND SPECIFIC PROTOCOL ADDENDA #1


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APPENDIX 5: TAIWAN SPECIFIC PROTOCOL ADDENDA #1


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APPENDIX 6: FLOW DIAGRAM OF PHASE 2 
 
 
 
 
 
 
 
Participant recruitment and 
informed consent 
Exclusion from study due to: 
Not meeting inclusion 
/exclusion criteria 
Declined to participate 
Other reasons 
Allocation 
1:1 randomization to either IMU-131 plus chemotherapy or 
chemotherapy alone (Day 0) 
Enrolment 
Screening Visit Assessment 
Days -21 to -1 
IMU-131 plus 
chemotherapy group 
receives 50 µg IMU-131 on 
Day 0, 14, 35, 77, 140 then 
every 63 days with 6 x 21-
day cycles of SOC 
chemotherapy starting Day 
0 
Study Completion 
Radiographic tumor assessment every 42 days until disease 
progression then follow for survival. Assess safety and humoral 
and cellular immunological responses until disease progression  
Analyze PFS endpoint after 24 progression events have been 
realized 
Secondary 
endpoint analysis 
Chemotherapy alone 
group receives 6 x 21-
day cycles of SOC 
chemotherapy starting 
Day 0 
Analyze OS endpoint after 24 deaths have been realized 
Primary endpoint 
analysis 
Patients in the study at the time of the primary final analysis will 
continue to be followed per the schedule of assessments until 
completion of the study. 
Supplementary 
analysis 

SAP_001.pdf: 
Confidential 
Imugene Limited 
IMU.ACS.001 
HERIZON: A Phase 1b/2 Open-label Study of IMU-131 HER2/neu Peptide 
Vaccine Plus Standard of Care Chemotherapy with Randomization in Phase 2 in 
Patients with HER2/neu Overexpressing Metastatic or Advanced Adenocarcinoma 
of the Stomach or Gastroesophageal Junction 
Statistical Analysis Plan 
Final Version 5.0 
12 July 2022 
Prepared by: 
PPD, Inc 
On behalf of Imugene Limited 
Level 3/62 Lygon St 
CARLTON VIC 3053 
NCT #: NCT02795988


Imugene Limited 
Final Statistical Analysis Plan, Version 5.0 
Protocol: IMU.ACS.001 
Date Issued: 12 July 2022 
 II
TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .................................................................................................... IV 
1.
INTRODUCTION ............................................................................................................ 1 
2.
OBJECTIVES ................................................................................................................... 2 
2.1. PRIMARY OBJECTIVE .......................................................................................................... 2 
2.2. SECONDARY OBJECTIVE ..................................................................................................... 2 
2.3. EXPLORATORY OBJECTIVE ................................................................................................. 2 
3.
INVESTIGATIONAL PLAN .......................................................................................... 3 
3.1. OVERALL STUDY DESIGN AND PLAN .................................................................................. 3 
3.2. STUDY ENDPOINTS ............................................................................................................. 4 
4.
GENERAL STATISTICAL CONSIDERATIONS ....................................................... 6 
4.1. REPORTING CONVENTION ................................................................................................... 6 
4.2. ANALYSIS WINDOW ........................................................................................................... 6 
4.3. SAMPLE SIZE CALCULATION .............................................................................................. 7 
4.4. RANDOMIZATION, STRATIFICATION, AND BLINDING .......................................................... 8 
4.5. ANALYSIS SET .................................................................................................................... 8 
5.
PATIENT DISPOSITION ............................................................................................. 10 
5.1. DISPOSITION ..................................................................................................................... 10 
5.2. PROTOCOL DEVIATIONS ................................................................................................... 10 
6.
DEMOGRAPHICS AND BASELINE CHARACTERISTICS .................................. 11 
6.1. DEMOGRAPHICS ................................................................................................................ 11 
6.2. BASELINE DISEASE CHARACTERISTICS AND PRIOR GASTRIC CANCER THERAPY ............. 11 
6.3. MEDICAL HISTORY ........................................................................................................... 12 
7.
TREATMENTS AND MEDICATIONS ....................................................................... 13 
7.1. PRIOR AND CONCOMITANT MEDICATIONS ........................................................................ 13 
7.2. CONCOMITANT PROCEDURES/SURGERIES ......................................................................... 13 
7.3. STUDY TREATMENTS ........................................................................................................ 13 
7.3.1. 
Extent of Exposure .................................................................................................... 13 
7.3.2. 
Treatment Compliance .............................................................................................. 14 
8.
EFFICACY ANALYSES ............................................................................................... 15 
8.1. PRIMARY EFFICACY ENDPOINT ......................................................................................... 15 
8.2. SECONDARY EFFICACY ENDPOINT .................................................................................... 16 
8.2.1. 
Progression-free Survival (PFS)............................................................................... 16 
8.2.2. 
Time to Progression (TTP) ....................................................................................... 18 
8.2.3. 
Disease Control Rate (DCR) .................................................................................... 19 
8.2.4. 
Objective Response Rate (ORR) ............................................................................... 20 
8.2.5. 
Duration of Objective Response (DOR) ................................................................... 20 
8.2.6. 
Investigator Disease Assessment (PFS, TTP, DCR, ORR, and DOR) ...................... 20 
8.2.7. 
Change in Tumor Size (CTS) .................................................................................... 21 
8.2.8. 
Sensitivity Analysis.................................................................................................... 21 


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8.2.8.1. 
Clinical Disease Progression ................................................................................ 21 
8.2.8.2. 
Death Due to Random Cause ................................................................................ 21 
8.2.8.3. 
Patients Randomized to Wrong Stratus ................................................................. 21 
9.
SAFETY ANALYSES .................................................................................................... 22 
9.1. ADVERSE EVENTS ............................................................................................................. 22 
9.2. CLINICAL LABORATORY EVALUATIONS ........................................................................... 23 
9.3. VITAL SIGN MEASUREMENTS ........................................................................................... 23 
9.4. ELECTROCARDIOGRAM ..................................................................................................... 23 
9.5. LVEF EVALUATION ......................................................................................................... 24 
9.6. ECOG PERFORMANCE STATUS ........................................................................................ 24 
10.
OTHER ANALYSES ...................................................................................................... 25 
10.1. 
IMMUNOLOGIC ASSESSMENTS ....................................................................................... 25 
10.1.1. 
Time-adjusted Area Under Curve (AUC) of Her-2-specific Antibodies................ 25 
10.2. 
SERUM AND BIOCHEMICAL MARKERS OF TUMOR PROGRESSION .................................. 26 
10.3. 
IN-VITRO INHIBITION OF TUMOR CELL GROWTH .......................................................... 26 
10.4. 
INTRA-TUMOR ANALYSIS .............................................................................................. 26 
11.
INDEPENDENT DATA MONITORING COMMITTEE .......................................... 27 
12.
SECONDARY ENDPOINT ANALYSIS ...................................................................... 28 
13.
CHANGES IN THE PLANNED ANALYSIS .............................................................. 29 
14.
REFERENCES ................................................................................................................ 30 
15.
APPENDICES ................................................................................................................. 31 
15.1. 
APPENDIX 1: SCHEDULE OF STUDY PROCEDURES – PHASE 2......................................... 31 
15.2. 
APPENDIX 2: IMPUTATION RULES FOR MEDICATION/ADVERSE EVENT DATE ............... 33 


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List of Abbreviations 
5-FU
5-fluorouracil
ADaM
Analysis Data Model
AEs
Adverse event(s)
ATC
Anatomical Therapeutic Chemical
AUC
Area Under Curve
B cell
B lymphocyte
BOR
Best overall response
CI
Confidence interval
CIV
continuous intravenous infusion
Cox-PH
Cox-proportional hazards regression model
CR
Complete Response
CRF
Case report form
CRP
C-reactive protein
CTCAE
National Cancer Institute’s Common Toxicity Criteria for Adverse Events
CTS
Change in Tumor Size
DCR
Disease Control Rate
DOR
Duration of Response
EAIR
Exposure-adjusted incidence rate
ECG
Electrocardiogram
ECOG
Eastern Cooperative Oncology Group
EoT
End of Treatment
EVAL
Evaluable Set
FAS
Full Analysis Set
GEJ
Gastroesophageal junction
GMFR
geometric mean fold rises
GMT
geometric mean titer
HER2/neu
Human epidermal growth factor receptor 2
HR
hazard ratio
ICF
Informed consent form
IDMC
Independent Data Monitoring Committee
IgG
Immunoglobulin G
IMU-131
Investigational product consisting of P467-CRM in Montanide adjuvant
ITT
Intent-to-Treat
IV
Intravenous(ly)
IxRS
Interactive Voice or Web Response System
LVEF
Left ventricular ejection fraction
MedDRA
Medical Dictionary for Regulatory Activities
NE
Not Evaluable
ORR
Objective Response Rate
OS
Overall survival
PD
Progressive Disease
PFS
Progression Free Survival
PP
Per-Protocol
PR
Partial Response
PT
preferred term


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RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
recommended phase 2 dose 
SAP 
Statistical analysis plan 
SD 
Stable Disease 
SOC 
System organ class 
T cell 
T lymphocyte 
TEAEs 
Treatment-emergent Adverse Events 
ToGA 
Trastuzumab for Gastric Cancer 
TTP 
Time to Progression 
WHODD 
World Health Organization Drug Dictionary 


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1. Introduction
This Statistical Analysis Plan (SAP) describes the analyses and data presentations for Imugene 
Limited protocol IMU.ACS.001 “HERIZON: A Phase 1b/2 Open-label Study of IMU-131 
HER2/neu Peptide Vaccine Plus Standard of Care Chemotherapy with Randomization in Phase 2 
in Patients with HER2/neu Overexpressing Metastatic or Advanced Adenocarcinoma of the 
Stomach or Gastroesophageal Junction”, which was amended on 17 Feb 2021 (Amendment No. 
3). The protocol has a 2-part design: Phase 1b and Phase 2, and this SAP is specifically for the 
Phase 2 study. It contains definitions of analysis populations, derived variables and statistical 
methods for the analysis of efficacy, safety and immunogenicity. 
The following analyses are planned in this study. 
•
Periodic safety analyses for Independent Data Monitoring Committee (IDMC) safety
reviews
•
The final analysis of progression free survival (PFS) after 24 evaluable PFS events have
been realized
•
The final analysis of overall survival (OS) after 24 deaths (at the end of study)
This SAP will only cover the secondary endpoint analysis at clinical cutoff of 24 evaluable PFS 
events and the primary endpoint analysis of OS at clinical cutoff of 24 OS events. The detail 
analyses for IDMC safety review is specified in the IDMC charter. 
Throughout this SAP, the treatment group will be referred to as the IMU-131 plus chemotherapy 
group and chemotherapy alone group. The purpose of the SAP is to ensure the credibility of the 
study findings by pre-specifying the statistical approaches to any data analysis prior to database 
lock. This SAP will be finalized and signed prior to the clinical database lock for the final PFS 
analysis at 24 evaluable progression events. Any significant changes after final PFS analysis and 
prior to final database lock for primary endpoint OS analysis after 24 deaths will be documented 
in Final SAP Amendment.  
All statistical analyses detailed in this plan will be conducted using SAS® 9.4 or later (SAS 
Institute Inc., Cary, North Carolina). 


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2. Objectives
2.1. 
Primary Objective 
The primary objective of this study is to evaluate the clinical efficacy of IMU-131 plus 
chemotherapy compared to chemotherapy alone based on OS. 
2.2. 
Secondary Objective 
The secondary objectives of this study are as follows: 
•
To evaluate other efficacy measures of IMU-131 plus chemotherapy compared to
chemotherapy alone including PFS, time to progression (TTP), disease control rate
(DCR), objective response rate (ORR), duration of objective response (DOR) and change
in tumor size (CTS) according to Response Evaluation Criteria In Solid Tumors version
1.1 (RECIST 1.1) for the progression evaluation of radiographic data.
•
To evaluate the safety profile of IMU-131 plus chemotherapy compared to chemotherapy
alone.
2.3. 
Exploratory Objective 
The exploratory objective of this study is as follows: 
•
To evaluate humoral and cellular immunogenicity data of IMU-131 plus chemotherapy
compared to chemotherapy alone including P467-specific antibodies (IgG), Her-2-
specific antibodies (IgG), vaccine-specific cytokine levels and regulatory and effector T
and B cells.
•
To evaluate the arm-specific associations between clinical outcome, intra-tumor T cells,
regulatory effector T and B cells, and serum and biochemical markers of tumor
progression.
•
To evaluate arm-specific associations between clinical outcome and HER2 and PD-L1
expression in tumor tissue.
•
To evaluate inhibition of in-vitro tumor cell growth and intra-cellular signaling processes
by Her-2-specific antibodies (IgG).


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3. Investigational Plan
3.1. 
Overall Study Design and Plan 
This phase 1b/2 protocol for patients with HER2/neu overexpressing metastatic or advanced 
adenocarcinoma of the stomach or GEJ has a 2-part design: Phase 1b and Phase 2. 
Phase 1b is an open-label, multicenter, single arm, dose escalation study with up to 18 enrolled 
to evaluate safety, tolerability and immunogenicity and to assess the Recommended Phase 2 
Dose (RP2D) of IMU-131 initiated 14 days prior to the start of chemotherapy. 
Phase 2 is an open-label, randomized, multicenter study to assess the clinical activity, 
immunogenicity, safety and tolerability of IMU-131. Phase 2 will enroll 36 patients and be 
conducted in the same centers as Phase 1b, with the addition of new centers as required to fulfill 
recruitment. Patient will be randomly assigned in a 1:1 ratio to either ‘IMU-131 plus 
chemotherapy’ or ‘chemotherapy alone’ groups.  
The length of Phase 2 will be approximately 30 months: 22 months’ recruitment and an 
estimated 8 months’ follow-up from completion of recruitment to realization of the required 
number of deaths. For a representation of the timeline of events in Phase 2 see Figure 1(Timeline 
for Phase 2). 
Figure 1: Timeline for Phase 2 
Screening Period 
Screening assessments or procedures will be conducted within 3 weeks prior to the start of study 
treatment, across at least 2 clinic visits. At the first screening visit, the patient will be asked to 
sign the informed consent form (ICF), the eligibility criteria will be assessed and screening for 
HER2/neu overexpression will be completed. All other screening procedures will be conducted 
at subsequent screening visits.  
Patient may be re-screened under certain situations as specified in the protocol. Before re-
screening, patient must sign a new ICF and will keep the same screening number. Screening 
procedures and test results/eligibility checks will be updated as part of re-screening.  
After completing all screening assessments, patients who meet all the inclusion and none of the 
exclusion criteria will proceed to the treatment period.  
Treatment Period 
Patient who are determined to be eligible for the study will be randomized on the Baseline/Day 0 
visit. Treatment for both groups will begin at the Baseline/Day 0 visit.  


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Patients in the IMU-131 plus chemotherapy group will receive vaccination of IMU-131 at 
Baseline/Day 0, Day 14, Day 35, Day 77, Day 140 and then every 63 days until disease 
progression. Patients in both the IMU-131 plus chemotherapy group and the chemotherapy alone 
group will receive chemotherapy starting at the Baseline/Day 0 visit and then every 21 days for a 
maximum of 6 cycles as clinically indicated or until disease progression, whichever occurs 
sooner. Chemotherapy will be consisting of:  
•
Cisplatin by intravenous administration at 80 mg/m2 on the first day of each cycle and
either 5-FU, 4000 mg/m2 CIV (administered as 1000 mg/m2/day as continuous infusion
for 96 hours on days 1 to 4 of each cycle) or capecitabine for 14 days at 2000 mg/m2/day,
orally (administered as 1000 mg/m2 twice daily morning and evening for a total of 2000
mg/m2/day on days 1 to 14 of each cycle);
•
Or oxaliplatin, by intravenous administration at 130 mg/m2 on Day 1 of each cycle and
capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice
daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle).
Patients who withdraw from the treatment or have progressive disease will undergo the End of 
Treatment (EoT) assessments as planned in the Schedule of Study Procedures. 
Post-treatment Follow-up Period 
After the EoT visit, the patient will be followed up every 42 days with radiographic assessment 
conducted (only for patients who withdrew from study before progressive disease was 
confirmed), survival follow-up assessment and post-study anti-cancer treatment recorded. 
3.2. 
Study Endpoints 
Primary Efficacy Endpoint 
•
OS measured from randomization to death due to any cause
Secondary Efficacy Endpoints 
•
PFS measured from randomization to date of earliest progressive disease (PD) based on
blinded central review according to RECIST 1.1 criteria, or to date of death from any
cause
•
TTP measured from randomization to date of earliest PD based on blinded central review
according to RECIST 1.1 criteria
•
ORR measured from randomization as the proportion of patients achieving a best overall
response of CR or PR based on blinded central review according to RECIST 1.1 criteria
•
DCR measured from randomization as the proportion of patients achieving a best overall
response of complete response (CR), partial response (PR) or stable disease (SD) based
on blinded central review according to RECIST 1.1 criteria
•
DOR measure from when earliest CR or PR is observed to PD or death due to any cause
based on blinded central review according to RECIST 1.1 criteria
•
Percentage CTS measured from baseline as the sum of diameters based on blinded central
review according to RECIST 1.1 criteria


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Exploratory Endpoints 
•
Values and changes from baseline in humoral and cellular immunogenicity data including
P467-specific antibodies (IgG), Her 2-specific antibodies (IgG), vaccine-specific
cytokine levels and regulatory and effector T and B cells
•
Values and changes from baseline in serum and biochemical markers of tumor
progression
•
Values and changes from randomization in Her-2-specific antibodies (IgG) inhibition of
in-vitro tumor cell growth
•
Values and changes from baseline in intra-tumor T cells and biochemical markers from
pre- and post-treatment tumor biopsies
Safety Endpoints 
•
Incidence of treatment-emergent adverse events (TEAE), Grade 3 or higher TEAEs,
serious TEAEs, and TEAEs leading to study treatment discontinuation
•
Incidence of treatment-emergent grade 3/4 clinical laboratory abnormalities
•
Changes and shifts from baseline in clinical laboratory, vital signs, and electrocardiogram
(ECG) parameters
•
Change from baseline in ECOG performance grade
•
Concomitant medication use
•
Treatment compliance


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4. General Statistical Considerations
4.1. 
Reporting Convention 
4.2. 
Analysis Window 
Baseline is defined as the last non-missing measurement prior to the first administration of any 
study treatment. For patients who were randomized but not treated, baseline will be the 
assessment taken on or before the randomization visit Baseline/ Day 0.  
The day of the first dose of any study drug will be defined as study Day 0. Study day are 
calculated relative to Day 0, as the difference between the date of interest and Day 0. 
For the post-baseline by-visit summaries of safety assessments, the nominal visits as captured on 
the eCRF page will be utilized.  
For the purpose of by-visit summaries of efficacy assessment (like the change in tumor size) and 
humoral immunogenicity data, the post-baseline visit mapping rules described in Table 4-1 and 
Table 4-2 will be used respectively. When multiple records fall in the same post-baseline visit 
window, the record with the study day closest to the target visit day will be chosen. In a case of a 
tie, the record with the earlier date will be chosen. Records that not chosen will be effectively 


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treated similarly to an unscheduled assessment and will still be included in all except the by-visit 
summaries.  
4.3. 
Sample Size Calculation 


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4.4. 
Randomization, Stratification, and Blinding 
Patients will be randomized using a permuted block randomization in a 1:1 ratio to receive IMU-
131 plus chemotherapy or chemotherapy alone treatment. Randomization will be performed 
centrally using an Interactive Voice or Web Response System (IxRS) and stratified by tumor 
stage at screening (III vs. IV). 
Phase 2 is an open-label study in which all the personnel will be unblinded except for the central 
radiography reviewers.  
4.5. 
Analysis Set 
The following analysis sets will be used: 


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ITT Set: All randomized patients. Patients will be analyzed as randomized. This analysis set will 
be used for primary efficacy analysis.  
Evaluable Set (EVAL): All randomized patients who receive any amount of study treatment and 
have at least one evaluable post-baseline tumor response. Patients will be analyzed as 
randomized. 
The Full Analysis Set (FAS): All randomized patients who receive any amount of study 
treatment. FAS analyses will be conducted on the basis of the randomized treatment. 
Safety Set: All randomized patients who receive any amount of study treatment. Patients will be 
analyzed as treated. All the safety analyses will be based on the Safety set. 
Per-protocol (PP) Set: A subset of the ITT set who will be selected based on the study drug 
experience (compliance and/or time on study drug) and major protocol deviations. The criteria 
for inclusion in the PP set will be finalized and documented prior to data base lock. Patients will 
be analyzed as randomized. 


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5. Patient Disposition
5.1. 
Disposition 
A summary of patient’s disposition will be presented based on the ITT set. The number and 
percentage of patients who received at least one dose of study treatment, and who discontinued 
study treatment will be presented by treatment group and in total, with specific primary reasons 
for treatment discontinuation presented as well. A similar summary will be repeated for study 
discontinuation. 
The enrollment will be summarized by study site and treatment group. 
The number and percentage of patients included in each analysis set will be provided. All the 
percentages will be based on the number of patients randomized.  
A Listing of patient treatment and study disposition will be provided. 
5.2. 
Protocol Deviations 
The protocol deviations will be defined in a separated study deviation rules document and will be 
identified and assessed by clinical research investigators or designee throughout the study. Any 
major protocol violation will be assessed prior to database lock, and to be considered for 
exclusion from Per-protocol Set. The number and percentage of subjects with major protocol 
deviations will be summarized overall and for each treatment group by type of deviation based 
on the ITT set. A listing of protocol deviations will be provided.  


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6. Demographics and Baseline Characteristics
The demographics and baseline characteristics will be summarized by treatment group and in 
total based on the ITT set. No inferential statistics will be presented. Individual patient listings 
will be provided to support the summary tables. 
6.1. 
Demographics 
Descriptive statistics for the following demographic variables will be provided: 
•
Age at consent (years)
•
Gender (Male, Female)
•
Primary race (Blank or African American, American Indian or Alaska Native, Asian,
Native Hawaiian or other Pacific Islander, White, Other, Not reported)
•
Ethnicity (Hispanic or Latino, Not Hispanic or Latino, Not reported, Unknown)
•
Height (cm)
•
Weight (kg)
•
Body mass index (BMI; kg/m2): calculated as (weight in kilograms) / (height in meters) 2
6.2. 
Baseline Disease Characteristics and Prior Gastric Cancer Therapy 
Descriptive statistics for the following disease characteristics will be provided: 
•
Baseline ECOG performance status
•
Baseline left ventricular ejection function (LVEF)
•
Initial tumor diagnosis type (Adenocarcinoma of gastroesophageal junction,
Adenocarcinoma of the stomach)
•
Disease Extent at Initial Diagnosis (Resectable, Borderline Resectable, Unresectable
locally advanced, Unresectable and metastatic)
•
Tumor stage at screening (Stage III, Stage IV)
•
Gross location of primary tumor (Type I, II, III, Not applicable)
•
Time since the initial diagnosis (in days): calculated as date of informed consent – date of
initial diagnosis + 1. If either month or month and day of initial diagnosis date is missing,
use the January 1. If day is missing, use the first day of the month. Imputation will not be
done for completely missing date.
•
Number of target lesions at baseline
•
Sum of lesion diameters (mm) of target lesions at baseline according to RECIST 1.1
The number and percentage of patients with prior gastric cancer therapy will be summarized as 
below: 
•
Prior gastric cancer surgery (yes, no)
•
Prior gastric cancer drug therapy (yes, no)


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•
Prior gastric cancer radiotherapy (yes, no)
Listings of prior gastric cancer surgery, prior gastric cancer drug therapy and prior gastric cancer 
radiotherapy will be provided, presenting the detail information captured on the specific eCRF 
pages. 
6.3. 
Medical History 
Medical history will be coded according to the Medical Drug Regulatory Activities (MedDRA), 
version 21.0 or higher. A frequency summary of medical history will be provided by system 
organ class (SOC) and preferred term (PT).  


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7. Treatments and Medications
7.1. 
Prior and Concomitant Medications 
Medications reported on the Prior and Concomitant Medications eCRF pages will be coded using 
World Health Organization Drug Dictionary (WHODD) March 2019 version and grouped into 
relevant categories based on the Anatomical Therapeutic Chemical (ATC) coding scheme.  
A prior medication is defined as any medication taken prior to the first administration of any 
study treatment (i.e. intake was stopped prior to the first administration). A concomitant 
medication is defined as any medication that is ongoing on/after the first administration or taken 
on/after the first administration.  
For the purpose of inclusion in prior and/or concomitant medication tables, incomplete 
medication start and stop dates will be imputed as described in Appendix 2. 
If start date is completely missing and end date is not prior to the first dose, then the medication 
will be classified as concomitant. If the start date is completely missing and the end date is prior 
to the first dose of study drug, then the medication will be classified as prior. If the end date is 
completely missing, then the medication will be classified as concomitant. Medications for 
which both the start and end dates are completely missing will be classified as both prior and 
concomitant. 
The number and percentage of patients with any prior medications will be summarized by ATC 
level 3 and generic drug name for each treatment group and in total. Similar frequency tables 
will be provided for concomitant medications. All summaries will be performed using the Safety 
set. 
A listing of prior and concomitant medications will be provided. 
7.2. 
Concomitant Procedures/Surgeries 
Concomitant procedure/surgery will be coded using the MedDRA version 21.0 or higher. A 
concomitant procedure/surgery is defined as any procedure/surgery conducted on or after the 
first administration of study treatment. Procedure/surgery with a missing date will be classified 
as concomitant. 
The number and percentage of patients with any concomitant procedure/surgery will be 
summarized by SOC and PT for each treatment group and in total using the Safety set. 
A listing of concomitant procedure/surgery will be provided. 
7.3. 
Study Treatments 
7.3.1. 
Extent of Exposure 
The treatment duration is defined as time interval in weeks between the date of first 
administration of any study treatment and the treatment end date inclusive, calculated as 
(treatment end date – date of the first administration of any study treatment + 1) / 7. The 
treatment end date will be the date of last IMU-131 injection if applicable, or the date of last 
chemotherapy treatment captured on the End of Treatment eCRF page, whichever is later. For 
patients who are still treatment ongoing at the clinical cutoffs, the treatment end date will be 


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earlier date of the clinical cutoff date and the maximum date among the exposure data captured 
on the IMU-131 Vaccination eCRF pages if applicable, and the specific Chemotherapy 
administration eCRF pages.  
Descriptive summary of treatment duration will be provided by treatment group. The total 
number of vaccinations, and the total number of cycles of chemotherapy administrated per 
patient will be summarized descriptively by treatment group. All summaries will be performed 
using the Safety set. 
7.3.2. 
Treatment Compliance 
The treatment compliance of IMU-131 vaccination will be calculated as the actual total number 
of vaccinations administrated divided by the prescribed number of vaccinations up to the disease 
progression or the data cutoff date and then multiplying 100. The acceptable range for 
compliance is defined as between 80% - 100%.  
Treatment compliance will be summarized descriptively and categorically in terms of < 80% and 
≥80% to ≤100%. 


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8. Efficacy Analyses
All imaging will be assessed by both investigators and a blinded central radiography review 
vendor, according to Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1). 
The blinded central review disease response assessments will be used as the primary measure for 
the efficacy endpoints, and the investigator disease assessments will be used as supportive 
measures for these analyses. All the disease assessments from the randomization until the clinical 
cutoff date or the end of study will be used in the deviation of the secondary efficacy endpoints, 
unless otherwise specified. 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
For all the time-to-event endpoints described in this section, the time interval will be reported in 
unit of week.  
8.1. 
Primary Efficacy Endpoint 
The overall survival (OS) is defined as the time from the randomization to the death due to any 
cause. Patients who have not died by the time of data cutoff or study end will be censored at the 
last known alive date, or the data cutoff date for final analysis if the last known alive date is not 
available yet.  
OS time will be calculated as Date of death (or date of last known alive/cutoff date) minus 
Randomization date + 1. 
 
 


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8.2. 
Secondary Efficacy Endpoint 
8.2.1. 
Progression-free Survival (PFS) 
PFS is defined as time in days from the randomization to the date of disease progression or death 
due to any cause on or prior to the clinical cutoff date, whichever occurred earlier. The disease 
progression will be defined as the radiological disease progression as assessed by blinded central 
reviewers. Therefore, duration of PFS in days is defined as the time between the date of 
randomization and the date of the first occurrence of one of the following events: 
•
Radiological disease progression per RECIST 1.1 as assessed by the blinded central
reviewers, i.e. a tumor response of PD is observed
•
Death due to any cause
The calculation of PFS is a two steps process. 
•
Determination of date of disease progression, which is the date of assessment
corresponding to the first date time that overall tumor response is “Progressive Disease”
on the Overall Tumor Response-RECIST eCRF
•
Calculation of duration from randomization to disease progression, death, or censoring
date as described in Table 8-1 as follows. In cases where a patient’s tumor is downstaged
to become surgically resectable, this is considered a response to treatment with
subsequent surgery being part of the patient’s normal clinical care. Such cases are
considered evaluable PFS event at time of confirmed progressive disease.
Table 8-1 Censoring Conventions for PFS 
Situation 
Date of Progression or Censoring 
Outcome 
Disease progression, and time interval 
between progression date and previous tumor 
assessment date with progression-free 
response is less than or equal to 98 days 
Earliest of: 
•
Date of first tumor assessment
showing new lesion
•
Date of first tumor assessment
with overall response of PD
Event 
Disease progression, and time interval 
between the progression date and the 
previous tumor assessment date with 
progression-free response is greater than 98 
days. 
Latest of: 
•
the last progression-free
assessment date
•
randomization date
Censored 
Death without any post-baseline radiological 
assessment, and time interval between death 
Death date 
Event 


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date and randomization date is less than or 
equal to 98 days 
Death without any post-baseline radiological 
assessment, and time interval between death 
date and randomization date is greater than 
98 days 
Randomization date 
Censored 
Death before documented progression, and 
time interval between death date and 
previous tumor assessment date with 
progression-free response is less than or 
equal to 98 days 
Death date 
Event 
Death before documented progression, and 
time interval between death date and 
previous tumor assessment date with 
progression-free response is greater than 98 
days 
The last progression-free assessment date 
Censored 
No death or disease progression, no 
treatment discontinuation due to 
symptomatic deterioration, and no 
subsequent anti-cancer therapy (i.e., systemic 
anti-cancer therapy, anti-cancer surgery, 
curative radiotherapy). 
Latest of 
•
the last progression-free
assessment date
•
randomization date
Censored 
Subsequent anti-cancer treatment (i.e., 
systemic anti-cancer therapy, anti-cancer 
surgery, radiotherapy) started prior to 
progression 
Latest of 
•
the last progression-free
assessment date prior to start of
anti-cancer treatment
•
randomization date
Censored 
Treatment discontinuation due to 
symptomatic deterioration prior to disease 
progression 
Latest of 
•
the last progression-free
assessment date before treatment
discontinuation date
•
randomization date
Censored 
An adequate disease assessment is a schedule or unscheduled assessment where the overall 
tumor assessment as assessed by blinded central reviewers is not missing and not unevaluable. 
Progression-free survival is calculated as follows.  
PFS = Analysis date defined above – randomization date + 1 
 
 


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8.2.2. 
Time to Progression (TTP) 
The time to progression is defined as the time from randomization to the disease progression on 
or prior to the clinical cutoff date.  
Similar with PFS, the calculation of TTP is a two steps process. 
•
Determination of date of disease progression, which is the date of assessment
corresponding to the first date time that overall tumor response is “Progressive Disease”
on the Overall Tumor Response-RECIST eCRF
•
Calculation of duration from randomization to disease progression, or censoring date as
described in Table 8-2 as follows. In cases where a patient’s tumor is downstaged to
become surgically resectable, this is considered a response to treatment with subsequent
surgery being part of the patient’s normal clinical care. Such cases are considered
evaluable for progression analysis at time of confirmed progressive disease.
Table 8-2 Censoring Conventions for TTP 
Situation 
Date of Progression or Censoring 
Outcome 
Disease progression, and time interval 
between progression date and previous tumor 
assessment date with progression-free 
response is less than or equal to 98 days 
Earliest of: 
•
Date of first tumor assessment
showing new lesion
•
Date of first tumor assessment
with overall response of PD
Event 
Disease progression, and time interval 
between the progression date and the 
previous tumor assessment date with 
progression-free response is greater than 98 
days. 
Latest of: 
•
the last progression-free
assessment date
•
randomization date
Censored 
Death without any post-baseline radiological 
assessment, and time interval between death 
date and randomization date is less than or 
equal to 98 days 
Death date 
Censored 
Death without any post-baseline radiological 
assessment, and time interval between death 
date and randomization date is greater than 
98 days 
Randomization date 
Censored 


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Death before documented progression, and 
time interval between death date and 
previous tumor assessment date with 
progression-free response is less than or 
equal to 98 days 
Death date 
Censored 
Death before documented progression, and 
time interval between death date and 
previous tumor assessment date with 
progression-free response is greater than 98 
days 
The last progression-free assessment date 
Censored 
No death or disease progression, no 
treatment discontinuation due to 
symptomatic deterioration, and no 
subsequent anti-cancer therapy (i.e., systemic 
anti-cancer therapy, anti-cancer surgery, 
curative radiotherapy). 
Latest of 
•
the last progression-free
assessment date
•
randomization date
Censored 
Subsequent anti-cancer treatment (i.e., 
systemic anti-cancer therapy, anti-cancer 
surgery, radiotherapy) started prior to 
progression 
Latest of 
•
the last progression-free
assessment date prior to start of
anti-cancer treatment
•
randomization date
Censored 
Treatment discontinuation due to 
symptomatic deterioration prior to disease 
progression 
Latest of 
•
the last progression-free
assessment date before treatment
discontinuation date
•
randomization date
Censored 
Time to Progression is calculated as follows.  
TTP = Analysis date defined above – randomization date + 1 
 
 
 
 
 
 
 
8.2.3. 
Disease Control Rate (DCR) 
The best overall response (BOR) for each patient will be derived based on blinded central review 
disease response assessments according to RECIST 1.1, using all the assessments from 
randomization until the data cutoff date or the end of study. If there is no post randomization 


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disease assessment, the BOR will be “No Post Randomization Assessment”; and if all the post 
randomization tumor responses are not evaluable, the BOR will be “Not Evaluable” (NE).  
 
 
 
 
 
8.2.4. 
Objective Response Rate (ORR) 
ORR is defined as the proportion of patients with a BOR of CR or PR after randomization. 
 
 
8.2.5. 
Duration of Objective Response (DOR) 
DOR is defined as the time from the earliest date when a tumor response of CR or PR is 
observed until the date of the first occurrence of disease progression or death due to any cause: 
Patients who don’t have disease progression or have not died on or prior to the analysis cutoff 
date will be censored at the last adequate disease assessment date, or the earliest date of the 
tumor response of CR or PR observed if no disease assessment is available afterwards. See 
Section 8.2.1 for the definition of disease progression and adequate disease assessment. 
 
 
 
 
 
8.2.6. 
Investigator Disease Assessment (PFS, TTP, DCR, ORR, and DOR) 
 
The same 
analysis method as described in Section 8.2.1, Section 8.2.2, Section 8.2.3, Section 8.2.4, and 
Section 8.2.5 will be applied. 


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8.2.7. 
Change in Tumor Size (CTS) 
 
 
 
8.2.8. 
Sensitivity Analysis 
8.2.8.1. 
Clinical Disease Progression 
Addition to original disease progression definition, clinical disease progression can be also 
considered as evidence of disease progression when there is no supportive radiographic 
assessment of PD. Clinical disease progression is “Progression Disease” leading to treatment 
discontinuation on eCRF end of treatment page identified by clinical assessment. The date of 
documented progression disease on eCRF end of treatment page will be used as the event date in 
a sensitivity analysis. The same full event and censoring rules show in Table 8-1 will be 
implemented as well but including clinical disease progression as evidence of disease 
progression when there is no supportive radiographic assessment of PD. 
 
 
 
 
8.2.8.2. 
Death Due to Random Cause 
Sensitivity analyses will be performed for the endpoints PFS and OS based on ITT set with 
assumption that patients dying due to any confirmed random event, like COVID-19, will be 
censored at the date of death. The same inferential analysis described in section 8.1 and section 
8.2.1 will be performed for the endpoint OS and PFS, respectively. 
8.2.8.3. 
Patients Randomized to Wrong Stratus 
Patients who randomized to the wrong stratus as a result of post-randomization review will be 
analyzed using the actual tumor stage as stratus factor provided it can be credibly argued that 
there is no between-arm bias in the application of the post-randomization review and specifically 
that the results of the review are not influenced by arm assignment. The analysis of survival and 
PFS will be repeated for the following modification: 
Analyze patients who randomized to the wrong stratus due to the wrong stage
classification determined at the time of randomization by the actual tumor stage. The
actual tumor stage can be assessed in a subsequent stage assessment.
The same inferential analysis described in section 8.1 and section 8.2.1 will be performed for the 
endpoint OS and PFS, respectively. 
Additional version of the survival analysis can be done by relaxing the censoring implemented as 
a result of cutoff and using vital status data collected after cutoff. 


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9. Safety Analyses
All the safety analyses will be performed using the Safety set. 
9.1. 
Adverse Events 
Adverse events (AE) will be coded using the MedDRA version 21.0 or higher. The severity of 
AEs will be graded according to National Cancer Institute’s Common Toxicity Criteria for 
Adverse Events version 5.0 (CTCTAE v5.0).  
A TEAE is defined as any AE occurring or worsening on or after the first administration of any 
study drug and within 30 days after the last administration date. Any AE for which the onset date 
is missing, and the end date is on or after the first dose of any study drug or missing will be 
counted as TEAE. For the purpose of inclusion in TEAE summaries, incomplete adverse event 
onset and end dates will be imputed as described in Appendix 2. 
A treatment-related TEAE is defined as any TEAE which is reported as “Possible Related”, 
“Probably Related” or “Definitely Related” to any study treatment on the eCRF pages. Any 
TEAE with a missing relationship or a relationship of “Not Applicable” will be considered as a 
treatment-related TEAE.  
A TEAE leading to treatment discontinuation is defined as any TEAE which is reported with an 
action of ‘Permanently discontinued’ taken with any study treatment on the eCRF pages. A 
TEAE leading to treatment reduction or interruption is defined as any TEAE which is reported 
with an action of ‘Dose decreased’ or ‘Stopped temporarily’ taken with any study treatment on 
the eCRF pages.  
Unless otherwise specified, for the frequency summaries of TEAE, the number and percentage of 
patients who experienced the specific event, and the number of events will be provided. For the 
number of patients with the specific event, patients with multiple occurrences of the specific 
event will be counted only once. For the number event, each occurrence of the specific event will 
be counted. The SOC will be presented in the descending order of the overall incidence and then 
alphabetically if two or more SOC have the same incidence; the PT within each SOC will be 
presented in the descending order of the overall incidence and then alphabetically if two or more 
PT have the same incidence. 
Frequency tables for the following TEAE categories will be provided by SOC and PT for each 
treatment group and in total. An overview summary table for these TEAE categories will be 
provided. 
•
TEAEs
•
TEAEs leading to treatment discontinuation
•
TEAEs leading to treatment reduction or interruption
•
Treatment-related TEAEs
•
Serious TEAEs
•
Grade 3 or higher TEAEs
•
TEAEs leading to death


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The TEAEs with a high level term of ‘Injection site reactions’ will be summarized by PT and 
treatment group. 
The TEAEs will be summarized by SOC, PT, the worst CTCAE grade and treatment group. At 
each level of patient summarization, the patient will be counted at the most severe occurrence if 
patient reported multiple occurrences of the same event. 
The TEAEs will also be summarized by the relationship to study treatment (as captured in the 
eCRF), SOC, PT and treatment group. At each level of the patient summarization, the patient 
will be counted at the most closely related occurrence if the patient reported multiple occurrences 
of the same event. 
A frequency summary table for the most frequent TEAEs will be provided by PT and treatment 
group. The most frequent TEAEs are defined as the PTs with a minimum of 5% patients’ 
incidence among the overall population.  
Listings of all AEs (including non-TEAEs), serious TEAEs, TEAEs leading to death, Grade 3 or 
higher TEAEs will be provided.  
9.2. 
Clinical Laboratory Evaluations 
The local clinical laboratory data (i.e. chemistry, hematology) will be graded according to 
CTCAE v5.0, for applicable tests. Grade 0 will be assigned for values that fall outside of the 
grading criteria. 
Actual value and change from baseline value will be descriptively summarized by visit and 
treatment group for each laboratory test. Shift tables in toxicity grades from baseline to each 
scheduled post-baseline visit will be provided as well for the laboratory tests with gradings. A 
shift table from baseline to the worst post-baseline grade will be provided for the laboratory tests 
with gradings. Unscheduled assessments will be considered as well when identifying the worst 
post-baseline grade.  
Listings of laboratory data will be provided. 
9.3. 
Vital Sign Measurements 
Vital sign measurements include height (cm), weight (kg), temperature (oC), blood pressure 
(mmHg) and pulse rate (beats/min). Descriptive statistics of baseline, actual value and change 
from baseline at each time point will be provided by visit and treatment group for vital signs 
except for height which will only be summarized at baseline. 
A listing of vital sign data will be provided. 
9.4. 
Electrocardiogram 
ECG parameters include heart rate (beats/min), PR interval (msec), QRS duration (msec) and 
QTc interval (msec). The ECG results will be interpreted by investigator and recorded as: 
normal, abnormal not clinically significant, or abnormal clinically significant on eCRF pages. 
Descriptive statistics of continuous ECG parameters and shift summary of ECG result 
interpretation from baseline will be provided by visit.  
A listing of ECG data will be provided. 


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9.5. 
LVEF Evaluation 
Actual value and change from baseline in LVEF (%) will be summarized by scheduled visit and 
treatment group. 
A listing of LVEF data will be provided.  
9.6. 
ECOG Performance Status 
The ECOG performance status will be summarized as a categorical variable by visit and 
treatment group. Descriptive summary table for change from baseline in ECOG performance 
grade will also be provided by visit. 
A listing of ECOG performance grade will be provided. 


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10. Other Analyses
All the summaries will be performed using the Safety set. 
10.1. 
Immunologic Assessments 
Collection of blood samples for humoral immunity will be performed for all patients as 
scheduled in the Schedule of Study Procedures. 
 
 
 
 
 
 
 
 
 
 
Listings of humoral immunogenicity data will be provided. 
Analyses of cellular immunogenicity data are conducted by Imugene and is documented 
separately. 
10.1.1. 
Time-adjusted Area Under Curve (AUC) of Her-2-specific Antibodies 


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Scatter plot to observe the relationship of time-adjusted AUC of Her-2-specific antibody from 
Baseline to Day 84 with change in tumor size from baseline to Day 84 will be presented. 
10.2. 
Serum and Biochemical Markers of Tumor Progression 
Analyses of serum and biochemical markers of tumor progression data are conducted by 
Imugene and is documented separately. 
10.3. 
In-Vitro Inhibition of Tumor Cell Growth 
Analyses of Her-2-specific antibodies (IgG) inhibition of in-vitro tumor cell growth data are 
conducted by Imugene and is documented separately. 
10.4. 
Intra-tumor Analysis 
Analyses of intra-tumor analysis data are conducted by Imugene and is documented separately. 


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11. Independent Data Monitoring Committee
An IDMC will regularly monitor the data from this Phase 2 study. The IDMC review meeting 
will be conducted after 8, 16 and 24 PFS events occur and at intervals of no less than once per 
year. The purpose of the data review is for safety evaluation. Further details of the IDMC review 
will be provided in the IDMC charter and separate analysis plan.  


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12. Secondary Endpoint Analysis
After 24 PFS events have been realized, the final analysis of PFS will be performed, which will 
also include an OS interim superiority analyses. A failure to meet statistical criterion for PFS will 
not prevent the final assessment of survival. 
As for the final analysis of PFS, and OS interim analysis, in addition to the efficacy analysis on 
endpoints PFS and OS, it also includes: 
•
Summary of treatment discontinuation and study discontinuation;
•
Summary of the demographics, baseline disease characteristics;
•
Summary of study treatment exposure;
•
Summary and analysis of other efficacy endpoints including TTP, DCR, ORR, DOR,
CTS;
•
Overview summary of TEAEs, summaries of all TEAEs by CTCAE grade, treatment-
related TEAEs, TEAEs leading to treatment discontinuation, Injection site reaction
TEAEs, serious TEAEs and TEAEs leading to death;
•
Summary of local laboratory tests, ECG tests, LVEF and ECOG performance grade;
•
Summary of AUC and time-adjusted AUC for Her-2-specific antibody and correlation of
the Her-2-specific antibody with change in tumor size, PFS and OS;
The same analysis methods will be used as full analysis described in previous sections of this 
SAP. 
 
  


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13. Changes in the Planned Analysis
 
  


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14. References
Brookmeyer, R. and Crowley, J. (1982) A confidence interval for the median survival time. 
Biometrics, 38, 29-41. doi:10.2307/2530286. 
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R. et al. New response 
evaluation criteria in solid tumours: revised RECIST guideline (version1.1). Eur J Cancer. 2009; 
45:228-47. 
Shiroiwa T, Fukuda T, Shimozuma K. Cost-effectiveness analysis of trastuzumab to treat HER2-
positive advanced gastric cancer based on the randomised ToGA trial. Br J Cancer, 
2011;105(9):1273-8. 
Wilson, E. B. (1927), “Probable Inference, the Law of Succession, and Statistical Inference,” 
Journal of the American Statistical Association, 22, 209–212. 


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15. Appendices
15.1. 
Appendix 1: Schedule of Study Procedures – Phase 2 
Scree
n 
Base-
line 
Week
2K 
(+/- 3d)
Week
3 
(+/- 3d)
Week 
5K 
(+/- 3d)
Week 
6 
(+/- 3d)
Week 
9 
(+/- 7d)
Week 
11K 
(+/- 7d)
Week 
12 
(+/- 7d)
Week 
15 
(+/- 7d)
Week 
18 
(+/- 7d)
Week 
20K 
(+/- 7d)
EoT 
VisitP 
(+/- 7d)
Post-
treatment 
FU Visit 
(+/- 7d) 
Study Days 
-21d
to
-1d
0 
14 
21 
35 
42 
63 
77 
84 
repeat 
every 
84 
days 
(+/- 7d)
105 
126 
repeat 
every 
 84 
days 
(+/- 7d)
140 
repeat 
every 
 63 
days 
(+/- 7d)
At least 
28 
(+/- 7) 
days 
after last 
dose 
Every 
42 
days after 
EoT 
Survival/anti-cancer 
treatment 
X 
IMU-131 Vaccination 
X 
X 
X 
X 
X 
ChemotherapyF 
X 
X 
X 
X 
X 
X 
Informed Consent 
X 
Demographics and 
prior medications 
X 
Medical History 
X 
Cancer History 
X 
Physical ExamO 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Weight and vital signs 
(temp, BP, pulse)L 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
ECOG performance 
status 
X 
X 
X 
X 
Radiographic 
AssessmentE 
X 
X 
X 
X 
XG 
Cardiac AssessmentH 
X 
X 
X 
Tumor biopsyI 
X 
XJ 
XJ 
Urine Pregnancy TestA 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HIV, HepatitisM 
X 
Hematology, 
ChemistryM 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Exploratory endpoint 
labsB 
X 
X 
X 
Immunology – 
humoralC 
X 
X 
X 
X 
X 
X 
X 
Immunology - 
cellularC 
X 
X 
X 


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Scree
n 
Base-
line 
Week
2K 
(+/- 3d)
Week
3 
(+/- 3d)
Week 
5K 
(+/- 3d)
Week 
6 
(+/- 3d)
Week 
9 
(+/- 7d)
Week 
11K 
(+/- 7d)
Week 
12 
(+/- 7d)
Week 
15 
(+/- 7d)
Week 
18 
(+/- 7d)
Week 
20K 
(+/- 7d)
EoT 
VisitP 
(+/- 7d)
Post-
treatment 
FU Visit 
(+/- 7d) 
Study Days 
-21d
to
-1d
0 
14 
21 
35 
42 
63 
77 
84 
repeat 
every 
84 
days 
(+/- 7d)
105 
126 
repeat 
every 
 84 
days 
(+/- 7d)
140 
repeat 
every 
 63 
days 
(+/- 7d)
At least 
28 
(+/- 7) 
days 
after last 
dose 
Every 
42 
days after 
EoT 
Concomitant 
Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
Procedures 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
A Negative urine pregnancy test required for women of childbearing potential at screening and prior to each vaccination. If positive urine test 
vaccination may be delayed until negative BHCG blood test. 
B 
A 1 x 10 mL whole blood sample to assess vaccine-specific cytokine levels and in-vitro inhibition of tumor cell growth will be obtained from 
each patient at Days 0, 84 then every 84 days and at EoT visit.  
C 
1 x 10 mL (i.e. 1 tube) whole blood sample for humoral immunity at Baseline, Days 21, 42, 63, 84, 126 then every 42 days and EoT visit and 
5 x 8 mL blood samples at Baseline, Days 84 then every 84 days and EoT visit for cellular immunity. To be taken prior to vaccination at 
Baseline visit.  
D 
Chemotherapy will be administered as a concomitant therapy to all patients as a 21-day regimen consisting of: cisplatin by intravenous 
administration at 80 mg/m2 on the first day of each cycle and either 5-FU, 4000 mg/m2 CIV (administered as 1000 mg/m2/day as continuous 
infusion for 96 hours on days 1 to 4 of each cycle) or capecitabine for 14 days at 2000 mg/m2/day, orally (administered as 1000 mg/m2 twice 
daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle), or capecitabine for 14 days at 2000 mg/m2/day, orally 
(administered as 1000 mg/m2 twice daily morning and evening for a total of 2000 mg/m2/day on days 1 to 14 of each cycle) and oxaliplatin, 
by intravenous administration at 130 mg/m2 on Day 1 of each cycle. Body weight to be measured and body surface area to be calculated based 
on weight and baseline height at the start of each 21-day chemotherapy cycle. Chemotherapy continues until ceased by the investigator as 
clinically indicated for the care of the patient. To document compliance while away from the clinic, patients will record capecitabine treatment 
in a patient diary.  
E     Radiographic assessment to occur within 14 days prior to Baseline Visit, then at Days 42, 84, 126 every 42 days thereafter. Radiographic 
assessment continues until disease progression according to RECIST 1.1 response criteria irrespective of whether patient has withdrawn from 
the study. 
F 
Chemotherapy continues for up to 6 cycles until disease progression or until ceased by the investigator as clinically indicated for the care of 
the patient, whichever occurs first.  
G 
Radiographic assessment according to RECIST 1.1 response criteria at post-treatment follow-up visit only for patients withdrawn from the 
study prior to disease progression. 
H 
Cardiac assessment will be based on assessment of medical history, physical examination, 12-lead ECG results and evaluation LVEF by 
echocardiography or MUGA scan at Screening, Days 84 then every 84 days and at EoT visit. 
I 
No tumor biopsy is required if a previous pathology result or archival tissue is available confirming HER2/neu expression consistent with 
Inclusion Criteria #6. 
J 
Optional Day 84 and post-progression tumor biopsy (which may be provided at any time during the post-treatment follow-up period).  
K 
Visit only for ‘IMU-131 plus chemotherapy’ group. 
L 
Record temperate 30min (+/- 10mins) after each IMU-131 vaccination. 
M Local laboratory testing. Safety lab samples can be drawn up to 72 hours before any on-study clinic visit. 
O 
A targeted, symptom directed physical examination may be performed at visits occurring after the Baseline Visit. 
P 
When progressive disease or withdrawal from study has been confirmed, EoT visit will be conducted at least 28 Days (+/- 7) after last dose of 
study medication. AEs to be checked at least 28 days after last study treatment per Section 9.2: Reporting Period. 


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15.2. 
Appendix 2: Imputation Rules for Medication/Adverse Event Date 
Missing onset dates (where UK and UKN indicate unknown or missing day and month 
respectively) 
•
UK-MMM-YYYY:
o
If the month and year are different from the month and year of the first dose of
study drug, assume 01-MMM-YYYY.
o
If the month and year are the same as the first dose of study drug month and year,
and the end date (after any imputation) is on or after the first dose of study drug,
then assume the date of the first dose of study drug.
o
If the month and year are the same as the first dose of study drug month, and year
and the end date (after any imputation) is prior to the first dose of study drug, then
assume the end date for the onset date.
•
DD-UKN-YYYY/UK-UKN-YYYY:
o
If the year is different from the year of first dose of study drug, assume 01-JAN-
YYYY of the collected year.
o
If the year is the same as the first dose of study drug year, and the end date (after
any imputation) is on or after the first dose of study drug, then assume the date of
the first dose of study drug.
o
If the year is the same as the first dose of study drug, and the end date (after any
imputation) is prior to the first dose of study drug, then assume the end date for
the onset date.
Missing end dates (where UK and UKN indicate unknown or missing day and month 
respectively): 
•
UK-MMM-YYYY: Assume the last day of the month;
•
DD-UKN-YYYY/UK-UKN-YYYY: Assume 31-DEC-YYYY
All the imputed end date will not be later than the last day on study. 


PPD Biostatistics and Programming
Statistical Analysis Plan (SAP) Client Approval Form
PPD CONFIDENTIAL AND PROPRIETARY
SOP-BST-05ar06
Effective Date:   19 September 2019
Page 1 of 1
Client:
Imugene Limited
Protocol Number:
IMU.ACS.001
Document Description:
Final Statistical Analysis Plan
SAP Title:
HERIZON: A Phase 1b/2 Open-label Study of IMU-131 
HER2/neu Peptide Vaccine Plus Standard of Care 
Chemotherapy with Randomization in Phase 2 in Patients 
with HER2/neu Overexpressing Metastatic or Advanced 
Adenocarcinoma of the Stomach or Gastroesophageal 
Junction
SAP Version Number:
5.0
Effective Date:
12 July 2022
Author(s):
For PPD: 
Approved by:
Date (DD-MMM-YYYY)
Date (DD-MMM-YYYY)