A Phase 1 Dose Escalation and Expansion Study of EO-3021, an Anti-claudin 18.2 (CLDN18.2) Antibody Drug Conjugate, in Patients With Solid Tumors Likely to Express CLDN18.2
Phase: PHASE1
Conditions: Stomach Neoplasm, Gastrointestinal Neoplasms, Digestive System Neoplasm, Neoplasms by Site, Neoplasms
Sponsor: Elevation Oncology

Protocol ELVCAP-002-01
Version 5.0 – 06 SEP 2024
 
Proprietary and Confidential 
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A Phase 1 Dose Escalation and Expansion Study of EO-3021, an 
Anti-claudin 18.2 (CLDN18.2) Antibody Drug Conjugate, in 
Patients with Solid Tumors Likely to Express CLDN18.2 
Elevation Oncology, Inc. 
 
 
Protocol Number: ELVCAP-002-01  
Investigational Product: EO-3021 
IND Number: 156681 
Protocol Version: 5.0 (06 SEP 2024) 
Replaces Protocol Version 4.0 (06 AUG 2023) 
 
 
 
 
Sponsor: 
Elevation Oncology, Inc.  
101 Federal Street 
Suite 1900 
Boston, MA 02110 
 
 
Confidentiality Statement 
This document, and the information it contains, are confidential and the proprietary  
property of Elevation Oncology. The information is not to be disclosed or transmitted  
to any party without the express approval of Elevation Oncology, or its agents,  
and any such unauthorized use or disclosure is expressly prohibited. 
 

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TABLE OF CONTENTS 
TABLE OF CONTENTS .................................................................................................................2 
LIST OF TABLES ...........................................................................................................................7 
LIST OF FIGURES .........................................................................................................................7 
LIST OF ABBREVIATIONS ..........................................................................................................8 
PROTOCOL SIGNATURE PAGE ...............................................................................................11 
SYNOPSIS. ....................................................................................................................................12 
1. 
INTRODUCTION ......................................................................................................24 
1.1. 
Clinical Application of CLDN18.2 in Solid Tumors ..................................................25 
1.2. 
EO-3021, Anti-claudin 18.2 MMAE Antibody Drug Conjugate ...............................26 
1.2.1. 
Nonclinical Pharmacology ..........................................................................................26 
1.2.2. 
Nonclinical Pharmacokinetics ....................................................................................26 
1.2.3. 
Nonclinical Safety Toxicology and Pharmacology ....................................................27 
1.2.4. 
Clinical Experience with Anti-Claudin 18.2 Agents and EO-3021 ............................27 
1.2.5. 
Rationale for the Implementation of Claudin 18.2 Expression in the 
Expansion Part of this Phase 1 Study .........................................................................29 
1.3. 
EO-3021 in Combination Therapy .............................................................................30 
1.3.1. 
Rationale for Combination with Ramucirumab ..........................................................31 
1.3.2. 
Rationale for Combination with Dostarlimab .............................................................31 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................32 
2.1. 
Primary Objective .......................................................................................................32 
2.2. 
Secondary Objectives .................................................................................................32 
2.3. 
Exploratory Objectives ...............................................................................................33 
2.4. 
Study Endpoints ..........................................................................................................33 
3. 
STUDY DESIGN .......................................................................................................33 
4. 
STUDY POPULATION .............................................................................................38 
4.1. 
Inclusion Criteria (All Parts and Treatment Arms, Unless Noted) .............................38 
4.2. 
Exclusion Criteria (All Parts and Treatment Arms, Unless Noted) ............................40 
4.2.1. 
Exclusion Criteria for Part B Expansion (All Treatment Arms B1, B2, B3) .............42 
4.2.2. 
Additional Exclusion Criteria for Combination with Ramucirumab (Arms 
A2 and B2) ..................................................................................................................42 

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4.2.3. 
Additional Exclusion Criteria for Combination with Dostarlimab (Arms A3 
and B3) ........................................................................................................................43 
5. 
ENROLLMENT AND REGISTRATION PROCEDURES ......................................43 
5.1. 
Enrollment of Patients ................................................................................................43 
5.2. 
Screen Failures ............................................................................................................43 
5.3. 
Registration of Patients ...............................................................................................44 
5.4. 
Replacement of Patients .............................................................................................44 
5.5. 
Blinding Procedures ....................................................................................................44 
6. 
STUDY TREATMENT ..............................................................................................44 
6.1. 
Selection of Starting Dose of EO-3021 (Monotherapy) .............................................45 
6.2. 
Selection of Starting Dose for Combination ...............................................................45 
6.2.1. 
EO-3021 ......................................................................................................................45 
6.2.2. 
Ramucirumab ..............................................................................................................46 
6.2.3. 
Dostarlimab .................................................................................................................46 
6.3. 
Study Part A:  Dose-Escalation Procedure .................................................................46 
6.3.1. 
Monotherapy Dose-Escalation (Arm A1) ...................................................................46 
6.3.2. 
Combination Dose-Escalation (Arms A2 and A3) .....................................................48 
6.3.3. 
Intermediate Dose Levels ...........................................................................................49 
6.3.4. 
Dose-Limiting Toxicity (DLT) ...................................................................................49 
6.3.5. 
Determination of Dose-Limiting Toxicities ...............................................................50 
6.3.6. 
Maximum Tolerated Dose ..........................................................................................50 
6.3.7. 
Recommended Phase 2 Dose ......................................................................................50 
6.3.8. 
Safety Overview and Dose-Escalation Decisions .......................................................51 
6.4. 
Study Part B:  Dose-Expansion at the RP2D ..............................................................51 
6.5. 
Dose Modifications .....................................................................................................51 
6.5.1. 
Dose Modification Rules ............................................................................................51 
6.5.2. 
Dose Modification Criteria for EO-3021 ....................................................................52 
6.5.2.1. 
Management of Nausea and/or Vomiting ...................................................................54 
6.5.2.2. 
Management of Infusion-related Reactions ................................................................56 
6.5.2.3. 
Management of Ocular Adverse Events .....................................................................57 
6.5.3. 
Dose Modification Criteria for Ramucirumab (CYRAMZA) ....................................58 
6.5.4. 
Dose Interruption, Delay, or Discontinuation Criteria for Dostarlimab 
(JEMPERLI) ...............................................................................................................60 

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6.5.4.1. 
Dose Modifications for Immune Checkpoint Inhibitor (ICI) Immune-
mediated Adverse Events ...........................................................................................60 
6.6. 
Duration of Therapy ...................................................................................................62 
6.7. 
Concomitant and Prohibited Medications ..................................................................63 
6.7.1. 
Concurrent Palliative Radiotherapy and Elective Procedures ....................................63 
6.7.2. 
Prohibited Medications ...............................................................................................64 
6.8. 
Study Termination and Patient Discontinuation .........................................................64 
6.8.1. 
Patient Discontinuation from Study Treatment ..........................................................64 
6.8.2. 
Study Treatment Beyond Progression ........................................................................65 
6.8.3. 
Site and Study Termination ........................................................................................65 
6.9. 
Accountability of Study Drug .....................................................................................66 
7. 
STUDY ASSESSMENTS AND EVALUATIONS ...................................................66 
7.1. 
Overview .....................................................................................................................66 
7.2. 
Screening Assessments ...............................................................................................66 
7.3. 
Study Treatment Assessments ....................................................................................68 
7.3.1. 
Cycle 1 (Days 1, 2, 3, 5, 8, and 15) ............................................................................68 
7.3.2. 
Cycles 2 and Beyond (on Day 1 of every cycle unless otherwise noted) ...................69 
7.4. 
End of Treatment Visit (within 28 ±3 Days of Last Dose) .........................................70 
7.5. 
Long-term Follow-up (Every 3 Months ±28 Days from Last Treatment) ..................71 
7.6. 
Correlative Studies ......................................................................................................71 
7.7. 
Pharmacokinetic and ADA Assessments ....................................................................72 
7.8. 
Adverse Events of Special Interest .............................................................................72 
8. 
RESPONSE EVALUATIONS AND MEASUREMENTS ........................................73 
9. 
DRUG FORMULATION, AVAILABILITY, ADMINISTRATION, AND 
TOXICITY INFORMATION ....................................................................................74 
9.1. 
Study Treatments ........................................................................................................74 
9.1.1. 
Labelling, Packaging, and Supply ..............................................................................74 
9.1.2. 
Preparation and Administration of Study Treatment ..................................................74 
9.1.2.1. 
EO-3021 ......................................................................................................................74 
9.1.2.2. 
Ramucirumab ..............................................................................................................75 
9.1.2.3. 
Dostarlimab .................................................................................................................75 
10. 
STATISTICAL CONSIDERATIONS .......................................................................75 
10.1. 
General Considerations ...............................................................................................75 

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10.2. 
Analysis Populations ..................................................................................................76 
10.3. 
Determination of Sample Size ....................................................................................76 
10.3.1. 
Dose Escalation (Part A) ............................................................................................76 
10.3.2. 
Expansion (Part B) ......................................................................................................76 
10.4. 
Analysis Methods .......................................................................................................77 
10.4.1. 
Disposition ..................................................................................................................77 
10.4.2. 
Demographics and Baseline Characteristics ...............................................................77 
10.4.3. 
Efficacy Analysis ........................................................................................................77 
10.4.4. 
Safety Analysis ...........................................................................................................78 
10.4.5. 
Pharmacokinetics ........................................................................................................78 
10.5. 
Planned Analyses ........................................................................................................79 
10.5.1. 
Final Analysis .............................................................................................................79 
10.5.2. 
Interim Analysis ..........................................................................................................79 
10.6. 
Stopping Rules ............................................................................................................79 
11. 
SAFETY REPORTING AND ASSESSMENT ..........................................................80 
11.1. 
Definitions ..................................................................................................................80 
11.1.1. 
Adverse Events ...........................................................................................................80 
11.1.2. 
Serious Adverse Event ................................................................................................80 
11.1.3. 
Adverse Event of Special Interest ...............................................................................82 
11.1.4. 
Recording and Reporting of Adverse Events .............................................................82 
11.1.5. 
Assessment of Adverse Events ...................................................................................83 
11.2. 
Serious Adverse Event Reporting by Investigators ....................................................83 
11.3. 
Recording of Adverse Events and Serious Adverse Events .......................................84 
11.3.1. 
Diagnosis Versus Signs and Symptoms .....................................................................84 
11.3.2. 
Persistent or Recurrent Adverse Events .....................................................................85 
11.3.3. 
Deaths .........................................................................................................................85 
11.3.4. 
Hospitalization, Prolonged Hospitalization, or Surgery .............................................85 
11.3.5. 
Pre-Existing Medical Conditions ................................................................................86 
11.3.6. 
New Cancers ...............................................................................................................86 
11.3.7. 
Pregnancy, Abortion, Birth Defects/Congenital Anomalies .......................................86 
11.3.8. 
Adverse Events of Special Interest (AESIs) ...............................................................87 
11.3.9. 
EO-3021 Overdose .....................................................................................................87 

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12. 
QUALITY ASSURANCE AND QUALITY CONTROL .........................................87 
12.1. 
Monitoring ..................................................................................................................87 
12.2. 
Audits and Inspections ................................................................................................88 
13. 
ETHICAL, FINANCIAL, AND REGULATORY CONSIDERATIONS .................88 
13.1. 
Institutional Review Board Approval .........................................................................88 
13.2. 
Regulatory Approval ..................................................................................................89 
13.3. 
Informed Consent .......................................................................................................89 
13.4. 
Confidentiality ............................................................................................................89 
13.4.1. 
Patient Confidentiality ................................................................................................89 
13.4.2. 
Investigator and Staff Information ..............................................................................90 
13.5. 
Financial Information .................................................................................................91 
14. 
RESEARCH RETENTION AND DOCUMENTATION OF THE STUDY .............91 
14.1. 
Amendments to the Protocol ......................................................................................91 
14.2. 
Documentation Required to Initiate the Study ...........................................................91 
14.3. 
Study Documentation and Storage .............................................................................92 
14.4. 
Data Collection ...........................................................................................................93 
15. 
PUBLICATION POLICY ..........................................................................................94 
16. 
REFERENCES ...........................................................................................................95 
17. 
APPENDICES ..........................................................................................................100 
Appendix A. Guidelines for Women of Childbearing Potential and Fertile Male 
Patients ......................................................................................................................100 
Appendix B. Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 ..............102 
Appendix C. Schedule of Assessments .....................................................................................106 
Appendix D. Immune Checkpoint Inhibitor Dose Modification and Toxicity 
Management Guidelines for Suspected Drug related Immune-mediated AEs 
(imAEs) .....................................................................................................................110 
Appendix E. Liver Chemistry Monitoring Guidance for Dostarlimab .....................................116 
Level 1 Monitoring ......................................................................................................................116 
Level 2 Monitoring ......................................................................................................................117 
 
 

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LIST OF TABLES 
Table 1 
Illustrative Dose Escalation of EO-3021 in Arm A1 (Monotherapy) .........................47 
Table 2 
Dose Escalation/De-escalation Rules for the BOIN Design .......................................47 
Table 3: 
Illustrative Dose Escalation of EO-3021 in Arm A2 (combination with 
ramucirumab) and Arm A3 (combination with dostarlimab) .....................................48 
Table 4: 
Dose Modification Guidelines for Non-Hematologic Toxicities Considered 
Related to Study Treatment ........................................................................................52 
Table 5: 
Dose Modification Guidelines Due to Hematologic Toxicities .................................53 
Table 6: 
Treatment Guidelines and Dose Modifications for Suspected Infusion-
related Reactions .........................................................................................................57 
Table 7: 
Dose Reductions for Ocular Adverse Events .............................................................58 
Table 8: 
Dosage Modifications for Ramucirumab (CYRAMZA) ............................................58 
Table 9: 
Examples of Strong CYP3A Inhibitors and Inducers .................................................64 
Table 10: ORR and 95% Confidence Intervals Based on N=40 or 20 .......................................77 
Table 11: Liver Event Increased Monitoring Criteria (Level 1 Liver Monitoring) ..................116 
Table 12: Liver Event Increased Monitoring Criteria (Level 2 Liver Monitoring) ..................117 
 
 
LIST OF FIGURES 
Figure 1: 
Study Design Overview ..............................................................................................36 
Figure 2: 
Study Schema for Arm 1 (EO-3021 Monotherapy) ...................................................36 
Figure 3: 
Study Schema for Arm 2 (Combination with Ramucirumab) ....................................37 
Figure 4: 
Study Schema for Arm 3 (Combination with Dostarlimab) .......................................37 
Figure 5: 
Liver Event Study Intervention Stopping Criteria and Liver Event Increased 
Monitoring Criteria with Continued Study Intervention ............................................62 
 

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LIST OF ABBREVIATIONS  
Abbreviation 
Definition 
ADA 
Anti-drug antibody 
ADC 
Antibody drug conjugate 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT (SGPT) 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
aPTT 
Activated Partial Thromboplastin Time 
ASCO 
American Society of Clinical Oncology 
AST (SGOT) 
Aspartate aminotransferase 
ATP 
Adenosine triphosphate 
AUC 
Area under the concentration time curve  
AUCINF 
Area under the curve from time zero extrapolated to infinity 
BCVA 
Best-corrected visual acuity 
BOIN 
Bayesian optimal interval 
BOR 
Best overall response 
BP 
Blood pressure 
BSA 
Body surface area 
BUN 
Blood urea nitrogen 
CAR-T 
Chimeric antigen receptor T-cell 
CBC 
Complete blood count 
CFR 
Code of Federal Regulations 
C1D1 
Cycle 1 Day 1 
C2D1 
Cycle 2 Day 1 
CI 
Confidence interval 
CL 
Clearance 
CLDN 
Claudin 
Cmax 
Maximum observed concentration 
CMP 
Comprehensive metabolic profile 
CNS 
Central nervous system 
COVID-19 
Coronavirus disease 2019 
CR 
Complete response 
CrCl 
Creatinine clearance 
CRF 
Case report form 
CRO 
Clinical research organization 
CSF 
Cerebrospinal fluid 
CSPC 
CSPC Megalith Biopharmaceutical Co., Ltd. 
CT 
Computerized tomography 
CTCAE 
Common terminology criteria for adverse events 
DCR 
Disease control rate 
DLT 
Dose-limiting toxicity 
dMMR 
mismatch repair deficient 
DOR 
Duration of response 
DRESS 
Drug reaction with eosinophilia and systemic symptoms 
DVT 
Deep vein thrombosis 
EC 
Ethics committee 
ECG 
Electrocardiogram 

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Abbreviation 
Definition 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
eGFR 
Estimated glomerular filtration rate 
EOT 
End of treatment 
EOX 
Epirubicin, oxaliplatin, and capecitabine 
FDA 
Food and Drug Administration 
FFPE 
Formalin-fixed paraffin-embedded 
GCP 
Good clinical practice 
GEJ 
Gastro-esophageal junction 
GI 
Gastrointestinal 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HED 
Human equivalent dose 
HEENT 
Head, eyes, ears, nose, and throat 
HER2 
Receptor tyrosine-protein kinase erbB-2 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
HNSTD 
Highest non-severely toxic dose 
HR 
Heart rate 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
ICI 
Immune checkpoint inhibitor 
ICMJE 
International Committee of Medical Journal Editors 
IgG1 
Immunoglobulin G1 
IHC 
Immunohistochemistry 
ILD 
Interstitial lung disease 
imAE 
Immune-mediated AEs 
IND 
Investigational New Drug 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
ISF 
Investigator study file 
IV  
Intravenous  
LFT 
Liver function test 
LMWH 
Low molecular weight heparin 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMAE 
Monomethyl auristatin E 
MRI 
Magnetic resonance imaging 
MRSD 
Maximum recommended starting dose 
MSI-H 
Microsatellite instability-high 
MTD 
Maximum tolerated dose 
nAb 
Neutralizing antibody 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NSCLC 
Non-small cell lung cancer 
NE 
Not evaluable 
NOAEL 
No observed adverse effect level 
OCT 
Optimal coherence tomography 
ORR 
Objective response rate 
OS 
Overall survival 

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Abbreviation 
Definition 
PD 
Progressive disease 
PD-1 
Programmed death receptor-1 
PD-L1 
Programmed death receptor ligand-1 
PE 
Pulmonary embolism 
PIS 
Patient information sheet 
PFS 
Progression-free survival 
PHI 
Protected health information 
PK 
Pharmacokinetic 
PO 
Orally 
PR 
Partial response 
PT 
Prothrombin time 
PTT 
Partial thromboplastin time 
Q3W 
Once every 3 weeks 
Q4W 
Once every 4 weeks 
QTcF 
QT interval corrected for heart rate by Fridericia’s formula 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
Recommended phase 2 dose 
RR 
Respiratory rate 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Stable disease 
SJS 
Stevens-Johnson syndrome 
SOC 
System organ class 
SpO2 
Oxygen saturation 
SRC 
Safety Review Committee 
STD 
Severely toxic dose 
t½  
Half-life 
TEAE 
Treatment emergent adverse event 
TEN 
Toxic epidermal necrolysis 
Tmax 
Time of maximum concentration 
TNF 
Tumor necrosis factor 
TRAE 
Treatment-related adverse events 
UA 
Urinalysis 
ULN 
Upper limit of normal 
VEGF 
Vascular endothelial growth factor 
VEGFR2 
Vascular endothelial growth factor receptor 2 
WBC 
White blood count 
 
 
 
 
 

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PROTOCOL SIGNATURE PAGE 
I have read this protocol and agree that it contains all necessary details for carrying out the study 
as described. I will conduct this study as outlined herein, including all statements regarding 
confidentiality. I will make a reasonable effort to complete the study within the time designated. I 
will provide copies of the protocol and access to all information furnished by the Sponsor to study 
personnel under my supervision. I will discuss this material with them to ensure that they are fully 
informed about the drug and the study. I will identify study personnel conducting study specific 
procedures and appropriately document their training and/or delegated responsibilities. I 
understand that the study may be terminated, or enrollment suspended at any time by the Sponsor, 
with or without cause, or by me if it becomes necessary to protect the best interests of the patients 
in the study. 
I agree to conduct this study in full accordance with all applicable regulations and Good Clinical 
Practice (GCP). 
 
 
_________________________________ 
 
 
 
_______________________ 
Signature of Investigator 
 
 
 
 
 
Date 
 
_________________________________ 
 
 
 
 
 
Print Name of Investigator 
 
 
 
_________________________________ 
 
 
 
_______________________ 
Signature of Sponsor  
 
 
 
 
 
Date 
Henry Koon, MD 
Vice President, Clinical Development 
Elevation Oncology, Inc. 
101 Federal Street 
Suite 1900 
Boston, MA 02110 

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SYNOPSIS. 
Sponsor: 
Elevation Oncology, Inc. 
101 Federal Street, Suite 1900 
Boston, MA 02110 
Protocol Title: 
A Phase 1 Dose Escalation and Expansion Study of EO-3021, an 
Anti-claudin 18.2 (CLDN18.2) Antibody Drug Conjugate, in Patients with 
Solid Tumors Likely to Express CLDN18.2 
Protocol 
Number: ELVCAP-002-01 
Phase of 
Development: 1 
Study Locations: Multicenter, International 
Number of Sites: Approximately 10 to 40 institutions will be recruited for participation in 
this study. 
Patient 
Population: 
Part A (Dose Escalation) enrolls patients with gastric/gastro-esophageal 
junction (GEJ) adenocarcinoma that are refractory to or intolerant of 
standard treatment, or for which no standard treatment is available). Part B 
(Expansion) enrolls patients with gastric/GEJ adenocarcinoma. 
Estimated 
Number of 
Patients: 
Approximately 70 patients are planned to be enrolled in Part A (Dose 
Escalation). The actual number enrolled will depend on overall safety and 
tolerability. Approximately 120 patients with gastric/GEJ adenocarcinoma 
are planned to be enrolled in Part B (Expansion). 
Primary 
Objective: 
To determine the recommended phase 2 dose(s) (RP2D) for the 
single-agent EO-3021, and when in combination with either ramucirumab 
or dostarlimab, for further exploration in patients with advanced/metastatic 
gastric/GEJ adenocarcinoma or advanced solid tumors that are likely to 
express CLDN18.2. 
Secondary 
Objectives: 
• To document the overall safety profile for EO-3021 when administered 
as a single agent, and when in combination with either ramucirumab or 
dostarlimab 
• To evaluate the pharmacokinetic (PK) profile of EO-3021 as a single 
agent, and when in combination with either ramucirumab or 
dostarlimab 
• To assess the immunogenicity of EO-3021 as a single agent, and when 
in combination with either ramucirumab or dostarlimab 
• To document any early indication of clinical efficacy in patients with 
advanced/metastatic gastric/GEJ adenocarcinoma or advanced solid 
tumors that are likely to express CLDN18.2 as a single agent, and when 
in combination with either ramucirumab or dostarlimab 
Exploratory 
Objectives: 
• To evaluate the association of anti-tumor activity of EO-3021 with 
CLDN18.2 expression by immunohistochemistry (IHC) (at various 
biomarker 
cut-offs) 
in 
advanced/metastatic 
gastric/GEJ 

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adenocarcinoma or advanced solid tumors that are likely to express 
CLDN18.2 as a single agent, and when in combination with either 
ramucirumab or dostarlimab 
• To evaluate if mechanistically-linked biomarkers correlate with 
clinical outcomes as a single agent, and when in combination with 
either ramucirumab or dostarlimab 
Study Design: 
This is a Phase 1 multicenter, open-label, dose escalation and expansion 
study conducted in patients with advanced unresectable or metastatic solid 
tumors that are likely to express CLDN18.2. With the release of a Protocol 
Administrative Letter dated 09April2024, only patients with gastric/GEJ 
adenocarcinoma will be enrolled in this study. Patients with other solid 
tumors likely to express CLDN18.2 will be excluded from trial 
participation. 
The study consists of 2 parts: Part A (Dose Escalation) and Part B 
(Expansion). Approximately 70 patients may be treated in Part A (Dose 
Escalation). Part A (Dose Escalation) consists of 3 arms: 
• Arm A1 (monotherapy): EO-3021 as a single agent in patients with 
gastric/GEJ adenocarcinoma that are refractory to or intolerant of 
standard treatment, or for which no standard treatment is available. 
Dose escalation will start with EO-3021 at 1.0 mg/kg following the 
Bayesian Optimal interval (BOIN) design with a target 
dose-limiting toxicity (DLT) rate of 25% for the maximum tolerated 
dose (MTD) (Yuan et al., 2016; Zhou et al., 2018). Dose escalation 
will proceed according to Figure 1 and Figure 2. Monotherapy dose 
escalation has completed at the time of this protocol amendment. 
• Arm A2 (combination with ramucirumab): EO-3021 in 
combination with ramucirumab in patients with gastric/GEJ 
adenocarcinoma that are refractory to or intolerant of standard 
treatment, or for which no standard treatment is available. 
Combination dose escalation will start with EO-3021 at 2.0 mg/kg 
intravenously (IV) once every 3 weeks (Q3W) following a standard 
3+3 design and proceed according to Figure 3. Ramucirumab will 
be administered at 10 mg/kg IV Q3W after EO-3021. The dose of 
Ramucirumab will be held constant while the dose of EO 3021 is 
escalated according to Figure 3 until RP2D/MTD is reached.   
• Arm A3 (combination with dostarlimab): EO-3021 in combination 
with the anti-PD1 inhibitor dostarlimab in patients with 
gastric/GEJ adenocarcinoma that are refractory to or intolerant of 
standard treatment, or for which no standard treatment is available. 
Dose escalation will start with EO-3021 at 2.0 mg/kg IV Q3W 
following a standard 3+3 design and proceed according to Figure 4. 
Dostarlimab will be administered at 500 mg IV Q3W after 
EO-3021. The dose of dostarlimab will be held constant while the 
dose of EO-3021 is escalated according to Figure 4 until 
RP2D/MTD is reached. 

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Dose escalation rules of each arm are outlined in Table 2 and discussed in 
Section 6.3. In all 3 arms, dose escalation follows the prespecified dose 
increments. Intermediate dose levels of EO-3021 as well as doses higher 
or lower than those described in Section 6.3 and/or alternative dosing 
frequencies (e.g., once every 4 weeks [Q4W]) may be explored, if 
warranted, based on overall safety, tolerability, and/or PK data if available 
and agreed upon by the SRC and Sponsor. At the discretion of the SRC 
and Sponsor, additional backfill patients may be included to further 
characterize the MTD/RP2D.  
Upon identifying the RP2D and/or MTD, Part B (Expansion) will 
commence in patients with gastric/GEJ adenocarcinoma. Part B 
(Expansion) aims to confirm the RP2D and to assess early signals of 
efficacy.  
A total of approximately 120 patients could be enrolled in Part B 
(Expansion). The Dose Expansion cohort consists of 3 arms: 
• Arm B1 (monotherapy): EO-3021 as a single agent in patients 
with gastric/GEJ adenocarcinoma who have received at least 1 
but no more than 3 prior lines of therapy in the advanced 
metastatic setting. Patients will be randomized to 2.0 mg/kg or 
2.5 mg/kg in a 1:1 fashion in monotherapy expansion. Prospective 
CLDN18.2 selection will be implemented during enrollment of 
the monotherapy expansion. 
• Arm B2 (combination with ramucirumab): EO-3021 in 
combination with ramucirumab in patients with locally advanced 
or metastatic gastric/GEJ adenocarcinoma who previously were 
treated with only 1 prior line of therapy in the metastatic setting. 
Prior fluoropyrimidine and platinum-containing chemotherapy is 
required. The dose of EO-3021 will be the RP2D/MTD 
determined in the combination dose escalation Arm A2. 
Ramucirumab will be administered at 10 mg/kg IV Q3W after 
EO-3021. Prospective CLDN18.2 selection will be implemented 
during enrollment of the combination expansion. 
• Arm B3 (combination with dostarlimab): EO-3021 in 
combination with dostarlimab in patients with locally advanced or 
metastatic gastric/GEJ adenocarcinoma who have not received 
any prior systemic therapy in the advanced metastatic setting. The 
dose of EO-3021 will be the RP2D/MTD determined in the 
combination dose escalation Arm A3. Dostarlimab will be 
administered at 500 mg IV Q3W after EO-3021. Prospective 
CLDN18.2 selection will be implemented during enrollment of 
the combination expansion. 
Prior to any study-specific activities, all patients or legal representatives 
must sign an informed consent form (ICF). Patients meeting the eligibility 
criteria are enrolled and treated at the dose level specified by the dose 
escalation scheme. Patients receive study treatment until disease 

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progression, unacceptable toxicity, or one or more protocol-specific 
treatment discontinuation criteria are met as described in Section 6.8.1. 
Logistically, the study is divided into observational windows of 21 days 
for data collection purposes; each 21-day period is considered a cycle of 
treatment.  
Patients will be treated on an outpatient basis and closely monitored for 
safety, being seen at the clinic on a weekly basis in the first cycle and then 
every 3 weeks when the patients receive dosing throughout therapy. Once 
off study treatment, survival data is collected via written communication 
(e.g., email, electronic medical record), telephone call, or clinic visits 
every 3 months (±28 days) from the date of last treatment until death, loss 
to follow-up, withdrawal of consent, or study termination by the Sponsor. 
Study Endpoints 
Safety endpoints: Dose-limiting toxicities, treatment-emergent adverse 
events (TEAEs), serious adverse events (SAEs), vital signs, and laboratory 
data. 
Efficacy endpoints:  Objective response rate (ORR; complete response 
[CR]+partial response [PR]), disease control rate (DCR; CR+PR+ stable 
disease [SD]), and time to event parameters (duration of response [DOR], 
progression-free survival [PFS] and overall survival [OS]). 
PK and anti-drug antibody (ADA) endpoints:  Serum PK parameters 
(maximum observed concentration [Cmax], area under the concentration 
time curve [AUC], and half-life [t½]) and ADA levels (percentage of 
subjects developing detectable ADAs and percentage of neutralizing 
antibodies [nAbs]) at prespecified time points. 
Inclusion 
Criteria: 
To be eligible for participation in the study, patients must meet the 
following inclusion criteria: 
1. Age ≥18 years 
2. Eastern Cooperative Oncology Group (ECOG) performance 
status 0 or 1 at screening 
3. Histologically and/or cytologically confirmed diagnosis of 
advanced metastatic gastric/GEJ adenocarcinoma not amenable to 
resection or radiation therapy with curative intent 
4. Availability of tumor tissue for evaluation of biomarker including: 
For Part A (Escalation) all arms: 
a. Archived formalin-fixed paraffin-embedded [FFPE] block 
or slides of tumor tissue from a previous biopsy obtained 
within last 24 months (Note: Only applicable to dose 
escalation and non-prospective selection portion of 
expansion arms), AND 
b. Fresh (new) biopsy prior to start of treatment, if medically 
feasible. Tumor biopsies should be considered by the 
treating physician in accordance with site standard 
procedures and obtained using a low-risk, medically routine 
procedure (Levit et al. 2019) (Note: Only applicable to dose 

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escalation and non-prospective selection portion of 
expansion arms) 
i. Note:  Tumor biopsy obtained prior to consent but 
no more than 3 months prior to Cycle 1 Day 1 
(C1D1) without any intervening treatment between 
the biopsy and C1D1 may be used to fulfill the fresh 
tumor tissue requirement with Sponsor approval 
c. Patients who meet only one of the above tumor tissue 
requirements may still be eligible for the study after 
discussion and approval from the Sponsor 
For Part B (Expansion) all arms: 
d. For the prospective selection portion of the expansion arms, 
a FFPE block or a minimum of 6 unstained slides of tumor 
tissue from a biopsy obtained within 6 months of 
enrollment must be available to submit for central review. 
(Note: If the patient received any CLDN18.2 directed 
therapy after the date of the archival biopsy a new biopsy 
must be performed and a FFPE block or 6 unstained slides 
must be available for central review.)  
e. For the prospective selection portion of expansion arms, 
patients must have tumor CLDN18.2 expression of greater 
than or equal to 25% 1+/2+/3+ by central laboratory review.  
5. Progressed on or after standard therapy, or are intolerant of 
available standard therapy, or there is no available standard 
therapy 
a. For Part A (Dose Escalation) with monotherapy EO-3021 
(Arm A1) and in combination with ramucirumab (Arm A2) 
or dostarlimab (Arm A3), there is no limit on the number of 
prior lines of therapy  
b. For Part B (Expansion) for monotherapy EO-3021 (Arm 
B1), at least 1 but no more than 3 prior lines of therapy in 
the advanced/metastatic setting is allowed  
c. For Part B (Expansion) for combination of EO-3021 plus 
ramucirumab (Arm B2), only 1 prior line of therapy in the 
advanced/metastatic 
setting 
is 
allowed; 
prior 
fluoropyrimidine and platinum-containing chemotherapy is 
required 
d. For Part B (Expansion) for combination of EO-3021 plus 
dostarlimab (Arm B3), no prior systemic therapy in the 
advanced/metastatic setting is allowed 
6. At least one measurable extra-cranial lesion as defined by 
Response Evaluation Criteria in Solid Tumors (RECIST) v1.1  
a. For Part A (Dose Escalation), patients with evaluable but 
non-measurable disease per RECIST v1.1 may be eligible 
after discussion and approval from the Sponsor 
7. Adequate organ function, defined as: 

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a. Hematology: defined as absolute neutrophil count 
(ANC) ≥1.5 
x 
109/L, 
platelet 
≥90 
x 
109/L, 
hemoglobin ≥9.0 g/dL (in the absence of transfusion within 
the last 7 days and use of growth factors within the last 
14 days prior to C1D1) 
i. For Arms A2 and B2 (Combination of EO-3021 
plus ramucirumab): platelet ≥100 x 109/L 
b. Renal function: defined as estimated glomerular filtration 
rate (eGFR) ≥40 mL/min (using the Cockcroft-Gault 
formula): 
Female creatinine clearance (CrCl) = ((140 - age in 
years) x weight in kg x 0.85) / (72 x serum creatinine 
in mg/dL) 
Male CrCl = ((140 - age in years) x weight in kg x 
1.00) / (72 x serum creatinine in mg/dL) 
i. For Arms A2 and B2 (Combination of EO-3021 
plus ramucirumab): 
1. The patient has adequate renal function as 
defined by a serum creatinine ≤1.5 times the 
upper limit of normal (ULN), or creatinine 
clearance (measured via 24-hour urine 
collection) ≥40 mL/minute (that is, if serum 
creatinine is >1.5 times the ULN, a 24-hour 
urine collection to calculate creatinine 
clearance must be performed 
2. The patient’s urinary protein is ≤1+ on 
dipstick or routine urinalysis (UA); if urine 
dipstick or routine analysis is ≥2+, a 24-hour 
urine 
collection 
for 
protein 
must 
demonstrate <1000 mg of protein in 
24 hours to allow participation in Arms A2 
and B2) 
c. Hepatic Function: 
i. Aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT) ≤2.5 x upper limit of 
normal (ULN) for patients without liver metastases 
or ≤5 x ULN if liver metastases are present 
ii. Total bilirubin ≤1.5 x ULN for patients without 
liver metastases or ≤3 x ULN if liver metastases are 
present, or the patient has bilirubin elevation due to 
Gilbert’s disease or a similar syndrome involving 
slow conjugation of bilirubin 
d. Coagulation function: International Normalized Ratio 
(INR) ≤1.5; Activated Partial Thromboplastin Time 
(APTT) ≤1.5 × ULN (patients on chronic anticoagulants are 
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i. Note: Patients on full-dose anticoagulation must be 
on a stable dose (minimum duration 14 days) of oral 
anticoagulant or low molecular weight heparin 
(LMWH). If receiving warfarin, the patient must 
have an INR ≤3.0. Patients should have no active 
bleeding (that is, no bleeding within 14 days prior 
to C1D1) or pathological condition present that 
carries a high risk of bleeding (e.g., tumor involving 
major vessels or known varices). 
8. Albumin level ≥3.0 g/dL 
9. Life expectancy >12 weeks 
10. Ability to understand the nature of this study, comply with 
protocol requirements, and give written informed consent 
11. Willingness of men and women of reproductive potential to 
observe conventional and effective birth control for the duration 
of treatment and for 6 months following study completion (or 
longer as required by local regulations including 6 months plus 
5 half-lives for female patients in South Korea and 3 months plus 
5 half-lives for male patients in South Korea). Please refer to 
Appendix A for detailed criteria for men and women of 
reproductive potential. 
Exclusion 
Criteria: 
Exclusion Criteria (All Parts and Treatment Arms, Unless Noted) 
To be eligible for participation in the study, patients must not meet any of 
the following exclusion criteria: 
1. Have non-adenocarcinoma histologic subtype of gastric/GEJ 
cancer (e.g., adenosquamous carcinoma, squamous carcinoma, 
etc.) 
2. Have unresolved toxicities from prior anticancer therapy, defined 
as toxicities (other than alopecia) not yet resolved to National 
Cancer Institute Common Terminology Criteria for Adverse 
Events (NCI-CTCAE) version 5.0, grade ≤1 or baseline. Patients 
with chronic grade 2 toxicities (except for Grade 2 peripheral 
neuropathy) may be eligible per the discretion of the Investigator 
after discussion and approval from the Sponsor 
3. Have a history of several allergic and/or anaphylactic reactions to 
known chimeric, human, or humanized antibodies, fusion proteins 
or known allergies to components of EO-3021, ramucirumab, or 
dostarlimab 
4. Have serious concurrent illness or clinically relevant active 
bacterial, fungal or viral infection including but not limited to the 
following: 
a. Active hepatitis B or C infection (whether on active 
antiviral therapy or not) 
i. For Arms A3 and B3 (Combination of EO-3021 
plus dostarlimab), patients must have documented 
negative Hepatitis B surface antigen (HBsAg) and 

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Hepatitis C antibody tests within 3 months prior to 
C1D1, see Section 4.2.3. 
b. Known human immunodeficiency virus (HIV) infection 
c. Other concurrent infectious disease requiring IV antibiotics 
within 2 weeks prior to C1D1 
Note: testing for HIV or hepatitis B or C is not required 
unless clinically indicated 
5. Have diagnosis of another malignancy, or history of systemic 
treatment for invasive cancer within last 3 years. Note: Patients 
with Stage I cancer who have received definitive local treatment 
and are considered unlikely to recur are eligible. Diagnosis of 
non-melanoma skin cancer, carcinoma in situ of the cervix or 
breast, or noninvasive tumor does not affect eligibility 
6. Have active central nervous system (CNS) disease involvement, 
defined by cerebrospinal fluid (CSF) cytology, magnetic resonance 
imaging (MRI) or computerized tomography (CT) 
a. Patients with asymptomatic CNS metastases are eligible if 
they have been clinically stable for at least 4 weeks prior to 
C1D1 and do not require interventions such as surgery, 
radiation, or any corticosteroid therapy for management of 
symptoms related to CNS disease. 
b. Patients with history of brain metastasis previously treated 
with radiation and/or surgical resection and without 
evidence of progression at screening are eligible, including 
those on stable low-dose of steroids (i.e., 10 mg orally (PO) 
daily of prednisone or equivalent) 
c. Screening for CNS disease is not required. Patients with 
history of CNS disease should have head imaging within 
the last 3 months documenting no active CNS disease. 
Patients with signs/symptoms concerning for CNS 
involvement should undergo head imaging to rule out 
active CNS disease at screening. 
7. Have history of non-infectious pneumonitis/interstitial lung disease  
8. Have peripheral neuropathy Grade ≥2 
9. Have active ocular surface disease defined as symptomatic or 
Grade ≥2 disease involving the cornea at baseline (based on 
screening ophthalmic examination) 
10. Have history of Grade ≥2 gastritis 
11. Are pregnant or breastfeeding   
12. Have previously received anti-CLDN18.2 antibody drug 
conjugates (ADCs) or any ADC containing an auristatin payload 
13. Have had major surgery (excluding tumor biopsy) within 28 days 
prior to C1D1 
14. Have 
received 
systemic 
anticancer 
therapy 
including 
chemotherapy, radiotherapy, biological therapy, targeted therapy, 
immunotherapy and investigational therapies within 28 days or 

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5 half-lives, whichever is shorter, before the first dose of EO-3021 
and the combination with ramucirumab or dostarlimab 
a. Use of palliative radiotherapy for bone metastases or local 
radiotherapy for pain relief within 2 weeks before the first 
dose of EO-3021 and the combination with ramucirumab or 
dostarlimab is allowed 
b. Ongoing use of drugs for bone metastasis related events 
(e.g., zoledronic acid) will not affect eligibility 
15. Have history of allogenic hematopoietic stem cell transplantation 
or solid organ transplantation  
16. Use of any drugs or substances known to be strong inducers or 
inhibitors of CYP3A enzymes (Table 9) and/or P-glycoprotein 
within 7 days prior or 3 half-lives, whichever is shorter, before the 
first dose of EO-3021 and the combination with ramucirumab or 
dostarlimab 
17. Have clinically significant cardiac disease, including but not 
limited to, any of the following within 6 months prior to C1D1: 
a. Myocardial infarction 
b. Unstable angina pectoris 
c. Cerebrovascular accident, transient ischemic attack, 
cerebral infarction 
d. Uncontrolled congestive heart failure (New York Heart 
Association Class III or IV) 
e. Uncontrolled or poorly controlled hypertension (defined as 
>160 mmHg systolic or >100 mmHg diastolic for >4 weeks 
despite standard medical management) 
f. Unstable cardiac arrhythmia requiring acute therapy 
(including torsades de pointes) 
g. Prolongation of the QT interval corrected for heart rate 
(QTcF) > 480 ms on at least 2 of 3 consecutive 
electrocardiograms (ECGs) and/or mean QTcF > 480 ms on 
all 3 ECGs during screening. Correction of suspected drug 
induced QTcF prolongation may be attempted at the 
investigator’s discretion if considered clinically safe. 
18. Have received any live vaccine within 30 days of enrollment. 
Vaccination against coronavirus disease 2019 (COVID-19) using 
vaccines that are authorized via the appropriate regulatory 
mechanisms (e.g., Emergency Use Authorization, Conditional 
Marketing Authorization, or Marketing Authorization 
Application) are not exclusionary. Note: mRNA and adenoviral-
based COVID-19 vaccines are considered non-live. If a 
COVID-19 vaccine is administered at any time, the date of 
COVID-19 vaccination must be entered in the eCRF. 
19. Patients who are not appropriate candidates for participation in this 
clinical study for any other reason as deemed by the investigator 
 

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Exclusion Criteria for Part B (Expansion) (All Treatment Arms B1, 
B2, B3) 
In addition to the main exclusion criteria, patients must not meet any of 
the following exclusion criteria: 
1. Have receptor tyrosine-protein kinase erbB-2 (HER2)+ disease as 
defined by American Society of Clinical Oncology-College of 
American Pathologists guidelines for gastric/GEJ 
adenocarcinoma 
2. Have non-measurable disease per RECIST v1.1 
 
Additional Exclusion Criteria for Combination with Ramucirumab 
(Arms A2 and B2) 
In addition to the main exclusion criteria, patients must not meet any of 
the following exclusion criteria: 
1. Received prior treatment with ramucirumab and other VEGFR2 
inhibitors 
2. Have experienced any Grade 3-4 gastrointestinal (GI) bleeding 
within 3 months prior to C1D1. 
3. Have a history of deep vein thrombosis (DVT), pulmonary 
embolism (PE), or any other significant thromboembolism (venous 
port or catheter thrombosis or superficial venous thrombosis are 
not considered “significant”) during the 3 months prior to C1D1. 
4. Have cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis 
(any degree) and with a history of hepatic encephalopathy or 
clinically meaningful ascites resulting from cirrhosis.  
a. Clinically meaningful ascites is defined as ascites from 
cirrhosis requiring diuretics or paracentesis. 
5. Is receiving chronic antiplatelet therapy, including dipyridamole or 
clopidogrel, or similar agents. Once-daily aspirin use (maximum 
dose 325 mg/day) is permitted. 
6. Have a prior history of GI perforation/fistula (within 6 months of 
first dose of protocol therapy) or risks factors for perforation. 
7. Have a serious or nonhealing wound, ulcer, or bone fracture within 
28 days prior to C1D1. 
8. Have a minor surgery/subcutaneous venous access device 
placement within 7 days prior to C1D1. 
9. The patient has elective or planned major surgery to be performed 
during the course of the clinical trial. 
 
Additional Exclusion Criteria for Combination with Dostarlimab 
(Arms A3 and B3) 
In addition to the main exclusion criteria, patients must not meet any of 
the following exclusion criteria: 

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1. Prior treatment with immune checkpoint inhibitors (ICI) including 
dostarlimab and other anti-programmed death receptor-1 (PD-1), 
anti-programmed death receptor ligand-1 (PD-L1), etc. 
2. Have an active autoimmune disease that has required systemic 
treatment in the past 2 years (i.e., with use of disease-modifying 
agents, 
corticosteroids, 
or 
immunosuppressive 
drugs). 
Replacement therapy (e.g., thyroxine, insulin, or physiologic 
corticosteroid replacement therapy for adrenal or pituitary 
insufficiency) is not considered a form of systemic treatment. 
3. Have experienced any of the following with prior immunotherapy: 
any immune-related adverse event ≥Grade 3, immune-mediated 
severe neurologic events of any grade (e.g., myasthenic 
syndromic/myasthenia 
gravis, 
encephalitis, 
Guillain 
Barré 
syndrome, or transverse myelitis), exfoliative dermatitis of any 
grade (Stevens-Johnson syndrome [SJS], toxic epidermal 
necrolysis [TEN], or drug reaction with eosinophilia and systemic 
symptoms [DRESS] syndrome), or myocarditis of any grade. Non-
clinically significant laboratory abnormalities are not exclusionary. 
4. Have documented presence of HBsAg at Screening or within 
3 months prior to C1D1. Patients with a negative HBsAg and 
positive Hepatitis B core antibody result are eligible only if HBV 
DNA is negative.  
5. Have a positive Hepatitis C virus (HCV) antibody test result at 
Screening visit or within 3 months prior to C1D1. Note: Patients 
with a positive HCV antibody test result due to prior resolved 
disease can be enrolled, only if a confirmatory negative HCV RNA 
test is obtained. 
 
Length of Study: The total duration of the study is planned to be approximately 3 years 
Investigational 
Product: 
EO-3021, ramucirumab, and dostarlimab are administered by IV infusion 
once every 21 days (±3 days).  
Patients should receive EO-3021 infused over 90 to 120 (±10) minutes for 
the first dose in C1D1. In the absence of infusion reactions, subsequent 
infusion time may gradually be decreased to 60 to 90 (±10) minutes, as 
tolerated. 
Patients 
should 
receive 
ramucirumab 
infused 
over 
60 (±10) minutes; subsequent infusion time may gradually be decreased to 
30 (±10) minutes as tolerated by the patient. Patients should receive 
dostarlimab infused over 30 (±10) minutes. 
Statistical 
Considerations: 
The sample size during Part A (Dose Escalation) of the study follows the 
BOIN design for Arm A1 (monotherapy) and traditional 3+3 design for 
Arm A2 (combination with ramucirumab) and Arm A3 (combination with 
dostarlimab. Approximately 70 patients are expected (approximately 
30 patients in Arm A1, 20 patients in Arm A2, and 20 patients in Arm A3). 
The actual sample size (including backfills) will depend on the number of 
DLTs observed and the number of doses explored.  

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For Part B (Expansion), approximately 120 patients will be treated at the 
RP2D, including approximately 80 patients in Arm B1 (monotherapy) and 
20 patients each in Arm B2 (combination with ramucirumab) and Arm B3 
(combination with dostarlimab).  
The analysis populations are defined as follows: 
• Safety Analysis Population includes all patients who received at 
least one dose of study treatment 
• DLT Evaluable Population includes all patients who received at 
least one dose of EO-3021 and complete the DLT observation 
period or experience DLT(s) within the DLT observation period 
• Efficacy Evaluable Population includes all patients who received 
at least one dose of EO-3021 and have baseline measurable disease 
and at least one post-baseline imaging assessment 
• PK Analysis Population will include all patients in the Safety 
Analysis Population who have at least one evaluable PK 
assessment 
• ADA Analysis Population will include all patients in the Safety 
Analysis Population who have at least one valid ADA result 
In general, descriptive analyses will be provided for all data including 
patient disposition, demographics, baseline characteristics, PK, safety, and 
efficacy. A Statistical Analysis Plan (SAP) will be finalized prior to the 
database lock. 
Safety analyses will include summary of incidence and severity of TEAEs, 
SAEs, laboratory values, physical exams, ECGs, and vital signs.   
Efficacy analyses will focus on patients enrolled in Part B (Expansion).  
However, patients in Part A (Dose Escalation) with the same type of 
disease and receiving the same dose as in Part B (Expansion) may be 
pooled into the appropriate disease cohorts as sensitivity analysis. For the 
ORR (CR or PR) endpoint, the Clopper-Pearson 95% confidence intervals 
(CIs) will be provided. Duration of response will be calculated among 
responders (CR and PR). Progression-free survival, OS and DOR will be 
analyzed using the Kaplan-Meier method. Graphical displays of data such 
as Kaplan-Meier curves and waterfall plots of best tumor changes from 
baseline will be provided.  
 

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1. 
INTRODUCTION 
Claudin 18 is a transmembrane protein that is a component of the tight junctions between epithelial 
or endothelial cell plates and plays an important role in maintaining cell polarity and signal 
transduction. Claudin 18 has 2 isoforms, CLDN18.1 and CLDN18.2; these isoforms are specific 
for pulmonary and gastric tissue, respectively (Sahin et al., 2008). CLDN18.2 expression in normal 
tissues is strictly limited to the differentiated epithelial cells that are typically buried within the 
gastric mucosa and are therefore largely inaccessible to monoclonal antibodies (Bergquist et al., 
2019). CLDN18.2 is overexpressed in several cancer types, including pancreatic, stomach, 
esophageal, lung, and ovarian cancers (Hong et al., 2020; Kim 2018; Wöll et al., 2014). An 
assessment of CLDN18.2 transcripts in human cancer tissues as determined by end-point real-time 
polymerase chain reaction demonstrated that 96%, 60%, 63%, and 41% of gastric, esophageal, 
pancreatic, and lung cancer samples, respectively, showed CLDN18.2 positivity; 77%, 78%, and 
80% of gastric, esophageal, and pancreatic cancer samples, respectively, were positive for 
CLDN18.2 protein expression as determined by immunostaining (Sahin, et al., 2008). The 
development of carcinogenesis leads to disruptions in tight junctions, which exposes the 
CLDN18.2 epitopes on the surfaces of tumor cells, thereby enabling the access of a CLDN18.2 
antibody (Sahin, et al. 2008).  
In recent years, CLDN18.2 has become a promising target for patients with gastric cancer and 
pancreatic cancer due to its high and selective expression within these malignant tumor types. Drug 
development for the CLDN18.2 target has primarily included monoclonal antibodies, antibody 
drug conjugates (ADCs), bispecific antibodies, and chimeric antigen receptor T-cell (CAR-T) 
therapies. Of these, the most advanced of antibody drugs targeting CLDN18.2 is the monoclonal 
antibody zolbetuximab (also referred to as claudiximab or IMAB362) developed by Ganymed 
(acquired by Astellas), for which the completed phase 3 SPOTLIGHT study showed a significant 
reduction in the risk of disease progression or death compared to placebo when combined with 
modified FOLFOX chemotherapy and administered to previously untreated, locally advanced 
unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma (Shitara et 
al., 2023). The phase 3 GLOW study reported an improvement in progression-free and overall 
survival for the addition of zolbetuximab to capecitabine and oxaliplatin chemotherapy as first-
line treatment for CLDN18.2-positive, receptor tyrosine-protein kinase erbB-2 (HER2)-negative, 
locally advanced unresectable or metastatic gastric/GEJ adenocarcinoma (Shah et al., 2023b). 
Other monoclonal antibodies, bispecific antibodies, and CAR-T therapies developed for this target 
are in phase 1 clinical trials (Zhang et al., 2020).   
Monomethyl auristatin E (MMAE) is a synthetic, highly potent mitotic inhibitor and is too toxic 
to be used as a chemotherapeutic drug by itself. However, in recent years, MMAE has widely been 
used as a cytotoxic payload component of ADCs for targeted therapy.  
EO-3021 (also referred to as SYSA1801 or CPO102) is an ADC that consists of an 
immunoglobulin G1 (IgG1) anti-CLDN18.2 monoclonal antibody conjugated via stable amide 
bonds with two MMAE moieties. The intended clinical indication for EO-3021 is advanced solid 
tumors that are likely to express CLDN18.2, including pancreatic cancer and adenocarcinoma of 
the stomach and gastroesophageal junction. Gastric and pancreatic cancers are among the 
malignancies with the highest unmet medical need. Gastric cancer remains a prevalent cancer 
worldwide and is responsible for over 1 million new cases in 2020 and an estimated 769,000 deaths 
(equating to 1 in every 13 deaths globally), ranking fifth for incidence and the fourth for mortality 

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globally (Sung et al., 2021). Most patients with gastric cancer present with unresectable or 
metastatic disease at the time of diagnosis, with a poor prognosis and median survival of less than 
a year (Hsu et al., 2020). Pancreatic cancer is presently the seventh leading cause of cancer death 
worldwide, with a 5-year survival rate of 9% (Rawla et al., 2019; Sung et al., 2021). Only about 
10% to 20% of pancreatic cancers are surgically resectable, and even after surgical resection, only 
about 20% of those patients live longer than 5 years (McGuigan et al., 2018; Neoptolemos et al., 
2018). The poor prognosis of these cancer types highlights the need for additional treatment 
approaches. New targeted therapies with better efficacy and safety profiles will greatly benefit 
these patients. 
Since high expression of CLDN18.2 is primarily restricted to malignant tissues, coupled with the 
selective binding to CLDN18.2 and conjugation with the potent mitotic inhibitor MMAE, 
EO-3021 has the potential to offer a specific targeted therapy for solid tumors expressing 
CLDN18.2. 
1.1. 
Clinical Application of CLDN18.2 in Solid Tumors 
Gastric cancer:  In an effort to develop CAR-T therapies for the treatment of gastric cancer, Jiang 
et al. evaluated CLDN18.2 protein expression by immunohistochemistry (IHC) in 24 types of 
human normal tissue samples (Jiang et al., 2019). They found that normal CLDN18.2 expression 
was only observed in stomach tissues. Normal tissues surrounding gastric tumors retained a high 
level of CLDN18.2 expression (≥2+ intensity). CLDN18.2 seemed to be homogeneously 
expressed in gastric cancer tissues. In metastatic gastric tumors, 77.4% (24/31) expressed 
CLDN18.2 and in 61.3% (19/31), CLDN18.2 was highly expressed (≥2+ intensity). Furthermore, 
the CLDN18.2 expression level in metastatic lesions is consistent with that in the corresponding 
primary gastric cancer tissues. 
Pancreatic cancer:  Sahin et al. reported that the CLDN18.2 transcripts were restricted to normal 
gastric tissue and were also detected in several epithelial tumor types (Sahin et al., 2008). In 7 of 
11 pancreatic adenocarcinomas examined, elevated mRNA levels of CLDN18.2 were noted. 
Various studies (Karanjawala et al., 2008; Lee et al., 2011; Tanaka et al., 2011; Hong et al., 2020) 
have also been carried out to assess the CLDN18.2 protein expression in different cancer types 
and have reported a range of 14% to 63% CLDN18.2 positivity rates in pancreatic tumors. The 
limited expression of CLDN18.2 in normal tissues coupled with the enhanced expression in 
pancreatic cancer suggests a clinically relevant application of therapies targeted to patients with 
CLDN18.2. 
Further supporting the clinical evaluation of EO-3021, clinical trials of the anti-claudin 18.2 
monoclonal antibody, zolbetuximab (IMAB362), have shown encouraging clinical activity. 
Patients with advanced gastric, GEJ or esophageal adenocarcinomas with moderate-to-strong 
CLDN18.2 expression in ≥50% of tumor cells received zolbetuximab intravenously (IV) every 
2 weeks for 5 planned infusions. Anti-tumor activity data were available for 43 patients, of whom 
4 achieved partial response (PR) (objective response rate [ORR] 9%) and 6 (14%) had stable 
disease (SD) for a clinical benefit rate of 23% (Türeci et al., 2019). Following this small but 
encouraging study, more clinical studies for zolbetuximab have been conducted, including the 
SPOTLIGHT and GLOW studies which reported reduction of disease progression and death 
(Shitara et al., 2023; Shah et al., 2023b).  

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1.2. 
EO-3021, Anti-claudin 18.2 MMAE Antibody Drug Conjugate 
EO-3021 has a molecular weight of approximately 147.6 kilodaltons (kDa, deglycosylated form). 
The drug product contains 10 mg/mL EO-3021 ADC in a 20 mM histidine buffer containing 
6% (w/v) sucrose and 0.02% (w/v) polysorbate 20 at pH 5.5. For clinical use, the EO-3021 drug 
product is diluted in 0.9% sodium chloride injection solution to obtain a solution for a single IV 
infusion. 
1.2.1. 
Nonclinical Pharmacology 
The binding specificity of EO-3021 was demonstrated in vitro using cellular binding assays. 
EO-3021 only binds to the HEK293 cells expressing human CLDN18.2 but not human CLDN18.1 
proteins. Upon binding with membrane CLDN18.2, EO-3021 is endocytosed and the active moiety 
MMAE is released. Incubation of EO-3021 with CLDN18.2-expressing cells induced cell cycle 
arrest at G2/M phase and apoptosis. As an IgG1 antibody, EO-3021 also retains substantial 
antibody-dependent cell-mediated and complement-dependent cytotoxic activities. 
The anti-tumor activity of EO-3021 was demonstrated in xenograft models. EO-3021 dose 
dependently inhibited tumor growth in 5 human cancer models that endogenously or ectopically 
expressed human CLDN18.2, including gastric (NUGC4 and NUGC4-CLDN18.2), pancreatic 
(PATU8988s 
and 
BxPC3-CLDN18.2), 
and 
non-small 
cell 
lung 
cancer 
(NSCLC) 
(NCI-H460-CLDN18.2) models. The effective dose for NUGC4 and PATU8988s models were 
10 mg/kg as a single dose at the beginning of 3-week period, and those for the ectopic models 
NUGC4-CLDN18.2, BxPC3-CLDN18.2, and NCI-H460-CLDN18.2 were 0.5, 2, and 4 mg/kg as 
single dose, respectively. EO-3021 showed superior anti-tumor efficacy than the conventional 
chemotherapeutic drugs gemcitabine and cisplatin. 
1.2.2. 
Nonclinical Pharmacokinetics 
Nonclinical pharmacokinetics (PK) of EO-3021 were studied following a single dose IV 
administration in Sprague Dawley rats and cynomolgus monkeys. The low, middle, and high dose 
levels for rats and monkeys were 1, 3, and 10 mg/kg and 0.5, 1.5, and 5 mg/kg, respectively. The 
intact EO-3021, total antibody (EO-3021 + naked antibody) and free MMAE were measured. 
The results showed no statistically significant sex differences in the primary PK parameters of 
EO-3021 including the maximum observed concentration (Cmax), area under the concentration time 
curve (AUC), half-life (t½) and drug clearance (CL) in all dose groups in both species. The 
exposure of ADC and total antibody in serum in different dose groups proportionally increased 
with the increasing administration doses tested. 
In both rats and monkeys, the PK behavior of ADC and total antibody was very similar. The mean 
t1/2 ranged from 47 to 132 hours in rats and 143 to 189 hours in monkeys. The median time of 
maximum concentration (Tmax) was 0.25 hours in rats and 0.5 hours in monkeys. The CL 
measurements ranged from 0.635 to 0.871 mL/h/kg in rats and 0.420 to 0.502 mL/h/kg in 
monkeys. 
The plasma exposure of free MMAE was minimal, less than 0.1%, as compared with the serum 
exposure of the intact ADC, suggesting that negligible MMAE shedding from EO-3021 occurred 
in the blood stream. The stability of ADC was further confirmed by in vitro serum/plasma 
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Anti-drug antibodies (ADA) were detected in both rats and monkeys, and more frequently in rats. 
Following a single IV administration, 1/6, 1/6, and 2/6 monkeys in the low, medium, and high 
dose groups, respectively, were positive for ADA, and they showed slightly reduced drug exposure 
than other animals that were ADA-negative. 
1.2.3. 
Nonclinical Safety Toxicology and Pharmacology 
The safety of EO-3021 has been evaluated in both in vitro systems and in animals. The maximum 
tolerated doses (MTDs) after single IV administration of EO-3021 were 75 and 30 mg/kg in 
Sprague Dawley rats and cynomolgus monkeys, respectively. The repeat-dose toxicity studies 
showed that the highest non-severely toxic doses (HNSTDs) were 25 and 20 mg/kg in Sprague 
Dawley rats and cynomolgus monkeys, respectively, after IV administration of EO-3021 once 
every 3 weeks for 6 weeks (3 doses in total) followed by a 4-week recovery period. The main toxic 
target organs are the digestive system (stomach) and lymph-hematopoietic system (thymus, bone 
marrow in sternum) in both species. In Sprague Dawley rats, the target organs also include the 
digestive system (ileum, liver), reproductive system (testes and epididymis), administration site, 
eyeballs, Hada’s gland, and mammary gland. Similar findings were observed in MMAE-treated 
Sprague Dawley rats. The pattern of effects observed in the toxicology studies is consistent with 
the anti-mitotic mechanism of action of MMAE and is similar to those observed with other 
antibody-MMAE conjugates (e.g., polatuzumab vedotin, Li et al., 2019). Additional 
EO-3021-related effects in the stomach are not unexpected based on the stomach-specific 
expression of CLDN18.2. All adverse effects had recovered or were recovering by the end of the 
4-week recovery period, with the exception of microscopic findings in the stomach, testes, and 
epididymides in rats.  
Safety pharmacological studies showed that EO-3021 had no potential effects on the central 
nervous system in rats, or on the cardiovascular system and respiratory systems in cynomolgus 
monkeys, with the no observed adverse effect level (NOAEL) of ≥50 mg/kg in rats and ≥20 mg/kg 
in monkeys following a single IV administration. 
In addition, in vitro tests confirmed that EO-3021 at concentrations of 5 mg/mL did not induce 
hemolysis or agglutination of rabbit red blood cells. 
Based on in vitro pharmacology, in vivo efficacy in mouse models, PK, and safety results, 
EO-3021 has the potential to be a specific, safe, and efficacious method to treat 
advanced/metastatic gastric/GEJ adenocarcinoma or advanced solid tumors that are likely to 
express CLDN18.2. 
1.2.4. 
Clinical Experience with Anti-Claudin 18.2 Agents and EO-3021 
There is limited data available for CLDN18.2-targeted agents. While there are currently no 
CLDN18.2-targeted agents approved commercially, there are ongoing clinical stage compounds 
in development, such as zolbetuximab. Early clinical safety data indicate common 
treatment-emergent adverse events (TEAEs) reported to include abdominal pain, decreased 
appetite, drug hypersensitivity, fatigue, pneumonia, vertigo, vomiting, weight loss, nausea, and 
general physical health deterioration. The majority of reported TEAEs were grade 1 or 2; grade 3 
nausea and vomiting were also reported.   
Nausea and vomiting were the most common TEAEs and occurred early during infusion of 
zolbetuximab. Given the organ-specific expression of CLDN18.2 in the stomach, the frequency of 

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these events was analyzed post hoc in relation to prior gastrectomy. Patients without prior 
gastrectomy were more likely to report nausea and vomiting.  Incidence of these TEAEs decreased 
over time as patients were exposed to repeated zolbetuximab infusions (Türeci et al., 2019). 
A first-in-human study of EO-3021 titled A Phase I Trial to Evaluate Safety, Tolerability, 
Pharmacokinetics, Immunogenicity and Initial Efficacy of SYSA1801 in the Treatment of 
CLDN18.2 Positive Advanced Malignant Solid Tumor (SYSA1801-CSP-001; NCT05009966) is 
ongoing in China with CSPC Megalith Biopharmaceutical Co., Ltd. (CSPC) as the Sponsor. 
Based on available data from CSPC, the Cmax of ADC was observed near the end of the infusion 
from 0.5 to 2 mg/kg IV once every 3 weeks (Q3W) after the first dose, with a mean Cmax of 8.10 
to 35.66 μg/ml and a mean AUCinf of 41.42 to 162.93 day*μg/ml. The Cmax and AUCinf increased 
proportionally to the increase in dose. The mean elimination t½ of ADC was 5.65 to 6.23 days.  
The most common adverse event (AE; >20%) related to EO-3021, by system organ class (SOC), 
were mainly: gastrointestinal (GI) disorders, mainly manifested as nausea (64%), vomiting (57%), 
upper abdominal pain (21%); eye disorders, manifested as dry eye (29%), corneal disorders (21%); 
and general disorders mainly manifested as asthenia (21%). See the Investigator’s brochure (IB) 
for a full summary of the safety profile.  
Initial preliminary clinical data presented by Wang et al. (2023) at the Annual Meeting of the 
American Society of Clinical Oncology (ASCO) highlighted the potential of EO-3021 to confer 
clinical benefit in patients with gastric cancer that expressed CLDN18.2 (defined as at least 1% of 
tumor cells with 1+ IHC by central laboratory testing). As of the data cut-off of 
05 November 2022, 33 eligible patients were enrolled: 6 patients with pancreatic cancer and 
27 patients with gastric cancer. Patients received 0.5 mg/kg to 3 mg/kg of EO-3021 administered 
IV Q3W as part of the dose escalation portion of the study (n=17); in the dose expansion portion 
of the study, patients (n=16) were treated at effective doses (2.0 mg/kg IV Q3W and 2.5 mg/kg IV 
Q3W). Twenty-one patients (gastric cancer n=17, pancreatic cancer n=4) were evaluable for 
efficacy per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. The ORR was 38.1% 
(8 PRs, including 4 confirmed PRs), and the disease control rate (DCR) was 57.1% (including 4 
SDs).  
In gastric cancer, the ORR was 47.1% (8 PRs, including 4 confirmed PRs) and the DCR was 
64.7%, including three patients with SD. The preliminary clinical data with an ORR of 47.1% in 
gastric cancer suggest EO-3021 has the potential to provide greater clinical benefit to patients with 
gastric cancer expressing CLDN18.2 than the currently available standard therapy (ORR 3-28%) 
(Wilke et al., 2014; Chan et al., 2019).  
The current study, ELVCAP-002-01 (NCT05980416), was initiated in August 2023 and is 
currently enrolling patients in the US and Japan. As of 10 JUNE 2024, 32 patients with gastric 
(n=17), GEJ (n=9), pancreatic (n=5), or esophageal (n=1) cancer have been enrolled in dose 
escalation at dose levels of 1.0 mg/kg to 2.9 mg/g IV Q3W. The safety profile remains favorable; 
the most common AEs (reported in ≥20% of patients) related to EO-3021 included nausea (53%), 
decreased appetite (41%), and fatigue (38%). There was no MMAE-associated toxicity reported 
(e.g., peripheral neuropathy, neutropenia, and elevations in liver function tests [LFTs]) in the initial 
safety dataset. Additionally, premedications with anti-emetics were strongly encouraged which 
seemed to reduce the rate of vomiting (3.8%). Four dose-limiting toxicities (DLTs) were observed 
in the 6 patients treated at 2.9 mg/kg IV Q3W. DLTs of Grade 3 encephalopathy and Grade 3 
fatigue were observed in 2 patients with advanced metastatic pancreatic cancer in the global 

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protocol. In addition, DLTS of Grade 3 decreased appetite and Grade 2 decreased appetite 
requiring a dose reduction were observed in 2 patients with advanced gastric cancer in the Japanese 
dose escalation cohort which was being conducted under a 3 + 3 design. The SRC declared the 
MTD to be 2.5 mg/kg IV Q3W based on the totality of data from the global and Japanese dose 
escalation arms. See the IB for a full summary of the safety profile. Early signs of clinical benefit 
and anti-tumor activity have also been observed. Of the 18 patients with gastric/GEJ 
adenocarcinoma who had measurable disease and were evaluable for tumor response per RECIST 
v1.1, tumor reduction was observed in ~50% of the patients, with 3 patients achieving tumor 
reduction of greater than 30% (2 confirmed PR; 1 as yet to be confirmed PR). In a CLDN18.2 
biomarker-enriched patient population (defined as CLDN18.2 in ≥20% of tumor cells at 2+/3+ 
IHC), the confirmed ORR was 42.8% in patients with gastric/GEJ adenocarcinoma.  
Taken together, these data support the continued evaluation of EO-3021 in gastric/GEJ 
adenocarcinoma that express CLDN18.2. 
1.2.5. 
Rationale for the Implementation of Claudin 18.2 Expression in the Expansion 
Part of this Phase 1 Study  
Clinical trials of the anti-CLDN18.2 antibody, zolbetuximab have demonstrated encouraging 
clinical efficacy; however responses require the majority (>70%) of tumors cells to express 
moderate-to-strong (2+/3+ IHC) expression of CLDN18.2 (Türeci et al., 2019; Sahin et al., 2021; 
Shitara et al., 2023). In the phase 2a study (NCT01197885, MONO 2013), patients with advanced 
gastric, GEJ or esophageal adenocarcinomas with moderate-to-strong CLDN18.2 expression 
demonstrated by IHC analysis in ≥50% of tumor cells received zolbetuximab IV every 2 weeks 
for 5 planned infusions. Antitumor activity data were available for 43 patients, of whom 4 achieved 
PR (ORR 9%) and 6 (14%) had SD for a clinical benefit rate of 23% (Türeci et al., 2019). All 4 PR 
responders had >70% CLDN18.2 expression in tumor cells, suggesting a possible correlation 
between CLDN18.2 expression and therapeutic benefit with zolbetuximab. 
A phase 2b study (NCT01630083, FAST 2015) evaluated zolbetuximab in combination with 
epirubicin, oxaliplatin, and capecitabine (EOX) chemotherapy in patients with advanced/recurrent 
gastric/GEJ adenocarcinoma. In this study, in patients with moderate-to-strong CLDN18.2 
expression in >70% of tumor cells, distinct improvements in progression-free survival (PFS) and 
overall survival (OS) were observed with zolbetuximab + EOX versus EOX. However, in patients 
where 40%-69% of tumor cells had moderate-to-strong CLDN18.2, neither PFS nor OS were 
significantly different between treatment arms (Sahin et al., 2021). Subsequently, two phase 3 
studies (SPOTLIGHT and GLOW) confirmed the benefit of adding zolbetuximab to chemotherapy 
in patients with gastric/GEJ adenocarcinoma that were CLDN18.2-positive, defined as 
moderate-to-strong CLDN18.2 expression in ≥75% of tumor cells (Shitara et al., 2023; Xu et al., 
2023). 
While these results with zolbetuximab, a monoclonal antibody to CLDN18.2, suggest high 
expression of CLDN18.2 is likely to correlate with patient benefit, EO-3021 is an anti-CLDN18.2 
antibody conjugated to a cytotoxic payload. It is plausible high expression of CLDN18.2 is not 
necessary for EO-3021’s mechanism of action. This hypothesis is supported by early clinical data 
from the ongoing study with EO-3021 conducted by CSPC; tumor shrinkage and confirmed tumor 
responses have been observed at a range of CLDN18.2 expression, including tumors with at least 
1+ (weak) CLDN18.2 expression in 5-97% of tumor cells (data on file). Therefore, enrollment into 

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the dose escalation portion of this phase 1 clinical trial is not dependent on CLDN18.2 expression 
provided the patients have a confirmed diagnosis of gastric/GEJ adenocarcinoma. For Part A all 
arms, the provision of tumor tissue (archival formalin-fixed paraffin-embedded [FFPE] biopsy 
obtained within the last 24 months and a fresh [new] FFPE tumor biopsy, if medically feasible) is 
required for retrospective exploratory analysis of CLDN18.2 as a potential predictive biomarker 
of response to EO-3021. Enrolling tumors with a broad range of CLDN18.2 expression will further 
support correlative analysis of clinical outcomes with varying CLDN18.2 expression in order to 
potentially establish a more defined cut-off that is clinically meaningful to predict and enrich for 
efficacy with EO-3021. It has been reported that the majority (~80%) of gastric, esophageal, and 
pancreatic adenocarcinomas express some level of CLDN18.2 (Sahin et al., 2008). Furthermore, 
EO-3021 exhibits bystander killing of tumor cells that do not express CLDN18.2 coupled with 
tumor heterogeneity (Fisher et al., 2013). Therefore, the benefits outweigh the risks for a 
preselection biomarker at this stage of development. 
In Part A of monotherapy dose escalation/backfill, 3 PRs were observed in tumors with higher 
CLDN18.2 expression and SD was the best response seen in tumors with little to no CLDN18.2 
expression to date. The assessment of CLDN18.2 expression and response for participants in 
Part A is ongoing. As the data around CLDN18.2 as a predictive biomarker for EO-3021 
monotherapy mature, the Sponsor plans to implement a prospective CLDN18.2 biomarker 
selection strategy to identify and enroll patients who would likely derive the most benefit from 
EO-3021 as monotherapy or in combination with ramucirumab or dostarlimab in future studies. In 
Part B (Expansion), expression of CLDN18.2 in 25% or more of tumor cells at 1+/2+/3+ IHC 
staining intensity as determined in a central laboratory will be required for enrollment in order to 
enrich for CLDN18.2-expressing tumors to support exploratory analyses of potential biomarker 
cutoffs in future studies.   
1.3. 
EO-3021 in Combination Therapy 
CLDN18.2, a tight junction protein normally expressed only on gastric mucosa, is highly 
expressed in gastric, pancreatic and other solid tumors (Türeci et al., 2011; Sahin et al., 2008). 
EO-3021 is an ADC composed of a monoclonal antibody targeting CLDN18.2 with an MMAE 
payload (Dan et al., 2023). EO-3021 selectively delivers the MMAE cytotoxic payload directly to 
cancer cells resulting in immunogenic cell death.  
First-line platinum-based doublet or triplet chemotherapy is the standard of care treatment in 
advanced (HER2 negative, programmed death receptor ligand-1 [PD-L1] low) gastric/GEJ 
adenocarcinoma with a median OS rate around 1 year (Kim et al., 2012; Baek et al., 2011; Al-
Batran et al., 2008; Koizumi et al., 2010; Koizumi et al., 2008; Yamada et al., 2015; Shah et al., 
2023; Lordick et al., 2022). Systemic therapy in the second and subsequent lines of therapy include 
ramucirumab in combination with paclitaxel (ORR 28%; median OS 9.6 months), or FOLFIRI 
(ORR 20-29%; median OS 6.4-6.7 months) if not used previously in the first-line setting (Fuchs 
et al., 2014; Sym et al., 2013; Assersohn et al., 2004). Additional options include single agent 
paclitaxel, docetaxel or irinotecan which achieve a median OS benefit between 5-9.5 months 
(Fuchs et al., 2014; Ford et al, 2014; Thuss-Patience et al., 2011). The low ORR and median OS 
rates of the established treatments in the second-line setting provide an opportunity for 
improvement. It is hypothesized that combining an established agent with EO-3021 may achieve 

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superior ORR and median OS in the first-line and second-line setting for patients with advanced 
or metastatic gastric/GEJ adenocarcinoma. 
1.3.1. 
Rationale for Combination with Ramucirumab 
Proangiogenic signaling through the vascular endothelial growth factor (VEGF) family of 
receptors, including the VEGF receptor 2 (VEGFR2) signaling pathway, is associated with 
increased tumor growth and invasion and reduced survival in patients with gastric cancer (Ferrara 
et al, 2003; Lieto et al, 2008; Peng et al, 2012). Ramucirumab (Cyramza) is a recombinant human 
IgG1 monoclonal antibody VEGFR2 antagonist (Miao et al, 2006). Ramucirumab is approved for 
use as a single agent or in combination with paclitaxel as a second-line therapy for patients with 
metastatic gastric or GEJ adenocarcinoma with disease progression on or after prior 
fluoropyrimidine- or platinum-containing chemotherapy based on the results from two phase III 
trials (REGARD, RAINBOW) (CYRAMZA, 2022; Fuchs et al, 2014; Wilke et al, 2014). The 
REGARD study exhibited a survival benefit with ramucirumab monotherapy for patients with 
advanced GC or GEJ adenocarcinoma who progressed after receiving first-line chemotherapy (5.2 
vs 3.8 months) (Fuchs et al, 2014). However, no difference in ORR between study arms was 
observed (3% vs. 3%) (Fuchs et al, 2014). In the RAINBOW study, patients with advanced GC or 
GEJ adenocarcinoma who progressed after receiving first-line chemotherapy and received 
paclitaxel in combination with ramucirumab had significantly longer median OS benefit compared 
to paclitaxel monotherapy (9.6 vs 7.4 months) and higher ORR (28% vs 16%) (Wilke et al, 2014). 
The established use of ramucirumab in 2L, a poor ORR rate with ramucirumab monotherapy 
(Fuchs et al, 2014), and the distinct mechanism of action of EO-3021 from ramucirumab provide 
the rationale for combining EO-3021 with ramucirumab to treat metastatic gastric/GEJ 
adenocarcinoma. 
For patients with advanced or metastatic gastric/GEJ adenocarcinoma whose disease has 
progressed on or after prior fluoropyrimidine- or platinum-containing chemotherapy, ramucirumab 
as a single agent or with the addition of paclitaxel is recommended by the NCCN, ASCO and 
ESMO (Shah et al, 2023; Lordick et al, 2022; Ajani et al, 2022). Known overlapping toxicities 
(reported in ≥20% of patients) between EO-3021 and ramucirumab in patients with gastric cancer 
include fatigue/asthenia and vomiting. Mitigation strategies for AEs are provided in Section 6.5 of 
this protocol.    
1.3.2. 
Rationale for Combination with Dostarlimab 
Programmed death receptor-1 (PD-1)/ PD-L1 inhibitors have been approved for use in 
combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line 
treatment of adult patients with advanced or metastatic GC/GEJ adenocarcinoma (KEYTRUDA, 
2020; OPDIVO, 2018) based on improvement of median survival and overall response rates (Rha 
et al, 2023; Sun et al, 2021; Doki et al, 2022; Janjigian et al, 2021).  
Preclinical evidence investigating PD-L1 expression in CLDN18.2-expressing gastric cancer cells 
correlated an increase in both PD-L1 upregulation and tumor infiltrating lymphocytes following 
treatment with an anti-CLDN18.2 monoclonal antibody (Qian et al, 2023). Additionally, clinical 
studies with MMAE-containing ADCs in solid tumors have provided evidence of MMAE-induced 
immunogenic cell death including recruitment and activation of immune cells, and extracellular 
release of adenosine triphosphate (ATP) (Liu et al, 2020; Trang et al, 2023; Heiser et al, 2024).  

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Dostarlimab (Jemperli) is an anti-PD-1 humanized IgG4 monoclonal antibody (Laken et al, 2016). 
While dostarlimab is not broadly approved for the treatment of GC/GEJ, it has accelerated 
approval as a single agent for the treatment of adult patients with mismatch repair deficient 
(dMMR) recurrent or advanced solid tumors including gastric/GEJ adenocarcinoma (JEMPERLI, 
2024). In patients with locally advanced or metastatic dMMR gastric/GEJ cancers who had 
progressive disease following systemic therapy, dostarlimab monotherapy achieved a confirmed 
ORR of 37.5% (Andre et al, 2021). While dostarlimab can induce responses in this subset of the 
patient population, combining dostarlimab with a targeted ADC may improve patient responses in 
a broader patient population with gastric/GEJ adenocarcinoma. Clinical trials investigating 
MMAE-containing ADCs directed towards various targets in combination with a PD-1 inhibitor 
in solid tumors, including gastric/GEJ cancer, are underway (NCT05934331; NCT05180799; 
NCT05941507). Notably, a nectin 4-directed ADC with an MMAE payload administered in 
combination with a PD-1 inhibitor yielded better outcomes compared to chemotherapy for first-
line treatment in patients with locally advanced or metastatic urothelial cancer (Powles et al, 2024) 
resulting in an FDA approval for eligible patients. 
The use of PD-1 inhibitors in the first line along with the distinct mechanism of action of EO-3021 
monotherapy support the rationale for combining EO-3021, which can activate antigen-presenting 
cells and immunogenic cell death, with dostarlimab, a PD-1 inhibitor, to treat gastric/GEJ cancer. 
Based on the potential enhancement of an immune response from a PD-1 inhibitor, it is 
hypothesized that combining EO-3021 with dostarlimab may result in improved outcomes in 
patients with locally advanced or metastatic gastric/GEJ adenocarcinoma. Overlapping toxicities 
(reported in ≥20% of patients) between EO-3021 and dostarlimab include anemia, nausea, and 
fatigue/asthenia; dostarlimab related immune-mediated adverse events with potential overlap with 
EO-3021 include pneumonitis and ocular toxicities. Mitigation strategies for AEs are provided in 
Section 6.5 of this protocol.   
2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Primary Objective 
The primary objective of this study is to determine the recommended phase 2 dose(s) (RP2D) for 
the single-agent EO-3021, and when in combination with either ramucirumab or dostarlimab, for 
further exploration in patients with advanced/metastatic gastric/GEJ adenocarcinoma or 
advanced solid tumors that are likely to express CLDN18.2. 
2.2. 
Secondary Objectives 
The secondary objectives of this study include the following: 
• To document the overall safety profile for EO-3021 when administered as a single agent, 
and when in combination with either ramucirumab or dostarlimab 
• To evaluate the PK profile of EO-3021 as a single agent, and when in combination with 
either ramucirumab or dostarlimab 
• To assess the immunogenicity of EO-3021 as a single agent, and when in combination with 
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• To document any early indication of clinical efficacy in patients with advanced/metastatic 
gastric/GEJ adenocarcinoma or advanced solid tumors that are likely to express CLDN18.2 
as a single agent, and when in combination with either ramucirumab or dostarlimab 
2.3. 
Exploratory Objectives 
The exploratory objectives of this study include the following: 
• To evaluate the association of anti-tumor activity of EO-3021 with CLDN18.2 expression 
by IHC (at various biomarker cut-offs) in advanced/metastatic gastric/GEJ 
adenocarcinoma or advanced solid tumors that are likely to express CLDN18.2 as a single 
agent, and when in combination with either ramucirumab or dostarlimab 
• To evaluate if mechanistically-linked biomarkers correlate with clinical outcomes as a 
single agent, and when in combination with either ramucirumab or dostarlimab 
2.4. 
Study Endpoints 
Safety endpoints: 
• Dose-limiting toxicities, TEAEs, serious adverse events (SAEs), vital signs, and laboratory 
data 
Efficacy endpoints: 
• ORR (complete response [CR]+PR), DCR (CR+PR+SD), and time to event parameters 
(duration of response, PFS and OS) 
PK and ADA endpoints: 
• Serum PK parameters (Cmax, AUC, t½) and ADA levels (percentage of subjects developing 
detectable ADAs and percentage of nAbs) at prespecified time points 
3. 
STUDY DESIGN 
This Phase 1 study is a multicenter, open-label, dose escalation and expansion study conducted in 
patients with advanced/metastatic gastric/GEJ adenocarcinoma or advanced solid tumors that are 
likely to express CLDN18.2.  With the release of a Protocol Administrative Letter dated 
09April2024, only patients with gastric/GEJ adenocarcinoma will be enrolled in this study. 
Patients with other solid tumors likely to express CLDN18.2 will be excluded from trial 
participation. 
The study design overview is presented in Figure 1 below. The study consists of 2 parts: Part A 
(Dose Escalation) and Part B (Expansion).  
Approximately 70 patients may be treated in Part A (Dose Escalation). Dose escalation consists of 
3 arms: 
• Arm A1 (monotherapy): EO-3021 as a single agent in patients with gastric/GEJ 
adenocarcinoma that are refractory to or intolerant of standard treatment, or for which no 
standard treatment is available. Dose escalation will start with EO-3021 at 1.0 mg/kg 
following the Bayesian Optimal interval (BOIN) design with a target DLT rate of 25% for 

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the MTD (Yuan et al., 2016; Zhou et al., 2018). Dose escalation will proceed according to 
Figure 1 and Figure 2.  
• Arm A2 (combination with ramucirumab): EO-3021 in combination with ramucirumab in 
patients with gastric/GEJ adenocarcinoma that are refractory to or intolerant of standard 
treatment, or for which no standard treatment is available. Combination dose escalation 
will start with EO-3021 at 2.0 mg/kg IV Q3W following a standard 3+3 design and proceed 
according to Figure 3. Ramucirumab will be administered at 10 mg/kg IV Q3W after 
EO-3021. The dose of Ramucirumab will be held constant while the dose of EO-3021 is 
escalated according to Figure 3 until RP2D/MTD is reached.   
• Arm A3 (combination with dostarlimab): EO-3021 in combination with the anti-PD1 
inhibitor dostarlimab in patients with gastric/GEJ adenocarcinoma that are refractory to or 
intolerant of standard treatment, or for which no standard treatment is available. Dose 
escalation will start with EO-3021 at 2.0 mg/kg IV Q3W following a standard 3+3 design 
and proceed according to Figure 4. Dostarlimab will be administered at 500 mg IV Q3W 
after EO-3021. The dose of dostarlimab will be held constant while the dose of EO-3021 
is escalated according to Figure 4 until RP2D/MTD is reached. 
Dose escalation rules of each arm are outlined in Table 2 and Table 3 and discussed in Section 6.3. 
In all 3 arms, dose escalation follows the prespecified dose increments. Intermediate dose levels 
of EO-3021 as well as doses higher or lower than those described in Section 6.3 and/or alternative 
dosing frequencies (e.g., once every 4 weeks [Q4W]) may be explored, if warranted, based on 
overall safety, tolerability, and/or PK data if available and agreed upon by the SRC and Sponsor.  
At the discretion of the SRC and Sponsor, additional backfill patients may be included to further 
characterize the MTD/RP2D. Patients enrolled to backfill do not contribute to the evaluation of 
the DLT rate in Part A1 dose escalation. Overall data from backfill and dose escalation cohorts 
will be used to determine the RP2D.   
Upon attaining an RP2D and/or MTD, Part B (Expansion) will commence in patients with 
gastric/GEJ adenocarcinoma. Part B (Expansion) aims to confirm the RP2D and to assess early 
signals of efficacy in the selected cancer patient populations. The Sponsor, in conjunction with the 
SRC, may decide to evaluate more than 1 dose in Part B. In this scenario, randomization may be 
employed to assign patients to 1 of 2 candidate RP2Ds. The sponsor may manage enrollment 
through the IRT to ensure balanced representation of evaluable patients in each arm by select 
covariates of interest (e.g., geographical location, lines of therapy, etc.) 
A total of approximately 120 patients could be enrolled in Part B (Expansion). The Dose Expansion 
cohort consists of 3 arms: 
• Arm B1 (monotherapy): EO-3021 as a single agent in patients with gastric/GEJ 
adenocarcinoma who have received at least 1 but no more than 3 prior lines of therapy in 
the advanced metastatic setting. Patients will be randomized to 2.0 mg/kg or 2.5 mg/kg in 
a 1:1 fashion in monotherapy expansion. Prospective CLDN18.2 selection will be 
implemented during enrollment of the monotherapy expansion.  
• Arm B2 (combination with ramucirumab): EO-3021 in combination with ramucirumab in 
patients with locally advanced or metastatic gastric/GEJ adenocarcinoma who previously 
were treated with only 1 prior line of therapy in the metastatic setting. Prior 

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fluoropyrimidine and platinum-containing chemotherapy is required. The dose of EO-3021 
will be the RP2D/MTD determined in the combination dose escalation Arm A2. 
Ramucirumab will be administered at 10 mg/kg IV Q3W after EO-3021. Prospective 
CLDN18.2 selection will be implemented during enrollment of the combination expansion. 
• Arm B3 (combination with dostarlimab): EO-3021 in combination with dostarlimab in 
patients with locally advanced or metastatic gastric/GEJ adenocarcinoma who have not 
received any prior systemic therapy in the advanced metastatic setting. The dose of 
EO-3021 will be the RP2D/MTD determined in the combination dose escalation Arm A3. 
Dostarlimab will be administered at 500 mg IV Q3W after EO-3021. Prospective 
CLDN18.2 selection will be implemented during enrollment of the combination expansion. 
In Part A (Dose Escalation), archived FFPE tumor tissue from a prior biopsy/surgical specimen 
(obtained within the last 24 months) and a fresh (new) tumor biopsy, if medically feasible, is 
required for retrospective evaluation of tumor CLDN18.2 expression performed by the Sponsor in 
a central laboratory. Tumor biopsy obtained prior to consent but no more than 3 months prior to 
Cycle 1 Day 1 (C1D1) without any intervening treatment between the biopsy and C1D1 may be 
used to fulfill the fresh tumor tissue requirement with Sponsor approval. Documentation of 
CLDN18.2 expression is not a requirement for participation in Part A (monotherapy and 
combination) of this study.   
In Part B (Expansion), a FFPE block or a minimum of 6 unstained slides of tumor tissue from a 
biopsy obtained within 6 months of enrollment must be available to submit for prospective central 
review. (Note: If the patient received any CLDN18.2 directed therapy after the date of the archival 
biopsy a new biopsy should be performed and FFPE block or 6 unstained slides must be available 
for prospective central review.) 
Prior to any study-specific activities, all patients or legal representatives must sign an informed 
consent form (ICF). Patients meeting the eligibility criteria are enrolled and treated at the dose 
level specified by the dose-escalation scheme. Patients receive study treatment until disease 
progression, unacceptable toxicity, or one or more protocol-specific treatment discontinuation 
criteria have been met as described in Section 6.8.1. Logistically, the study is divided into 
observational windows of 21 days for data collection purposes; each 21-day period is considered 
a cycle of treatment.  
Patients will be treated on an outpatient basis and will be closely monitored for safety, being seen 
in the clinic on a weekly basis in the first cycle and then every 3 weeks when the patients receive 
dosing throughout therapy. Once off study treatment, survival data will be collected via written 
communication (e.g., email, electronic medical record), telephone call, or clinic visits every 
3 months (±28 days) from the date of last treatment until death, loss to follow-up, withdrawal of 
consent, or study termination by the Sponsor. 

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Figure 1: 
Study Design Overview 
 
Figure 2: 
Study Schema for Arm 1 (EO-3021 Monotherapy) 
 
 
GC = Gastric cancer; GEJ = Gastro-esophageal junction; IV = Intravenous; MTD = Maximum tolerated dose; 
Q3W = Once every 3 weeks; RP2D = Recommended phase 2 dose 

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Figure 3: 
Study Schema for Arm 2 (Combination with Ramucirumab) 
 
DLT = Dose-limiting toxicity; GC = Gastric cancer; GEJ = Gastro-esophageal junction; IV = Intravenous; 
MTD = Maximum tolerated dose; Q3W = Once every 3 weeks; RP2D = Recommended phase 2 dose; SRC = Safety 
Review Committee; TBD = to be determined 
Figure 4: 
Study Schema for Arm 3 (Combination with Dostarlimab) 
 
DLT = Dose-limiting toxicity; GC = Gastric cancer; GEJ = Gastro-esophageal junction; IV = Intravenous; 
MTD = Maximum tolerated dose; Q3W = Once every 3 weeks; RP2D = Recommended phase 2 dose; SRC = Safety 
Review Committee; TBD = to be determined 

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4. 
STUDY POPULATION 
Patient selection criteria include general criteria applicable to all patients (Section 4.1) as well as 
additional exclusion criteria included in Section 4.2.1 and Section 4.2.3 for combination of 
EO-3021 with ramucirumab and dostarlimab, respectively. 
4.1. 
Inclusion Criteria (All Parts and Treatment Arms, Unless Noted) 
To be eligible for participation in the study, patients must meet the following inclusion criteria: 
1. Age ≥18 years 
2. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 at screening 
3. Histologically and/or cytologically confirmed diagnosis of advanced metastatic 
gastric/GEJ adenocarcinoma not amenable to resection or radiation therapy with curative 
intent  
4. Availability of tumor tissue for evaluation of biomarker including: 
For Part A (Dose Escalation) all arms: 
a. Archived FFPE block or slides of tumor tissue from a previous biopsy obtained 
within last 24 months (Note: Only applicable to dose escalation and 
non-prospective selection portion of expansion arms) AND 
b. Fresh (new) biopsy prior to start of treatment, if medically feasible. Tumor biopsies 
should be considered by the treating physician, in accordance with site standard 
procedures, and obtained using a low-risk, medically routine procedure (Levit et 
al., 2019) (Note: Only applicable to dose escalation and non-prospective selection 
portion of expansion arms)   
i. Note:  Tumor biopsy obtained prior to consent but no more than 3 months 
prior to C1D1 without any intervening treatment between the biopsy and 
C1D1 may be used to fulfill the fresh tumor tissue requirement with Sponsor 
approval 
c. Patients who meet only one of the above tumor tissue requirements for retrospective 
testing may still be eligible for the study after review and approval from the 
Sponsor. 
For Part B (Expansion) all arms: 
d. For the prospective selection portion of the expansion arms, a FFPE block or a 
minimum of 6 unstained slides of tumor tissue from a biopsy obtained within 
6 months of enrollment must be available to submit for central review. (Note: If the 
patient received any CLDN18.2 directed therapy after the date of the archival 
biopsy a new biopsy must be performed and a FFPE block or 6 unstained slides 
must be available for central review.)  
e. For the prospective selection portion of expansion arms, patients must have tumor 
CLDN18.2 expression of greater than or equal to 25% 1+/2+/3+ by central 
laboratory review.  
5. Progressed on or after standard therapy, or are intolerant of available standard therapy, or 
there is no available standard therapy 
a. For Part A (Dose Escalation) with monotherapy EO-3021 (Arm A1) and in 
combination with ramucirumab (Arm A2) or dostarlimab (Arm A3), there is no 
limit on the number of prior lines of therapy  
b. For Part B (Expansion) for monotherapy EO-3021 (Arm B1), at least 1 but no more 
than 3 prior lines of therapy in the advanced/metastatic setting is allowed  

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c. For Part B (Expansion) for combination of EO-3021 plus ramucirumab (Arm B2), 
only 1 prior line of therapy in the advanced/metastatic setting is allowed; prior 
fluoropyrimidine and platinum-containing chemotherapy is required 
d. For Part B (Expansion) for combination of EO-3021 plus dostarlimab (Arm B3), 
no prior systemic therapy in the advanced/metastatic setting is allowed 
6. At least one measurable extra-cranial lesion as defined by RECIST v1.1  
a. For Part A (Dose Escalation), patients with evaluable but non-measurable disease 
per RECIST v1.1 may be eligible after discussion and approval from the Sponsor 
7. Adequate organ function, defined as: 
a. Hematology: defined as absolute neutrophil count (ANC) ≥1.5 x 109/L, 
platelet ≥90 x 109/L, hemoglobin ≥9.0 g/dL (in the absence of transfusion within 
the last 7 days and use of growth factors within the last 14 days prior to C1D1) 
i. For Arms A2 and B2 (Combination of EO-3021 plus ramucirumab): 
platelet ≥100 x 109/L 
b. Renal 
function: 
defined 
as 
estimated 
glomerular 
filtration 
rate 
(eGFR) ≥40 mL/min (using the Cockcroft-Gault formula): 
Female CrCl = ((140 - age in years) x weight in kg x 0.85) / (72 x serum 
creatinine in mg/dL) 
Male CrCl = ((140 - age in years) x weight in kg x 1.00) / (72 x serum 
creatinine in mg/dL) 
i. For Arms A2 and B2 (Combination of EO-3021 plus ramucirumab): 
1. The patient has adequate renal function as defined by a serum 
creatinine ≤1.5 times the upper limit of normal (ULN), or creatinine 
clearance (measured via 24-hour urine collection) ≥40 mL/minute 
(that is, if serum creatinine is >1.5 times the ULN, a 24-hour urine 
collection to calculate creatinine clearance must be performed 
2. The patient’s urinary protein is ≤1+ on dipstick or routine urinalysis 
(UA); if urine dipstick or routine analysis is ≥2+, a 24-hour urine 
collection for protein must demonstrate <1000 mg of protein in 
24 hours to allow participation in Arms A2 and B2) 
c. Hepatic Function: 
i. Aspartate 
aminotransferase 
(AST) 
and 
alanine 
aminotransferase 
(ALT) ≤2.5 x upper limit of normal (ULN) for patients without liver 
metastases or ≤5 x ULN if liver metastases are present 
ii. Total bilirubin ≤1.5 x ULN for patients without liver metastases or 
≤3 x ULN if liver metastases are present, or the patient has bilirubin 
elevation due to Gilbert’s disease or a similar syndrome involving slow 
conjugation of bilirubin 
d. Coagulation function: International Normalized Ratio (INR) ≤1.5; Activated 
Partial Thromboplastin Time (APTT) ≤1.5 × ULN (patients on chronic 
anticoagulants are eligible) 
i. Note: Patients on full-dose anticoagulation must be on a stable dose 
(minimum duration 14 days) of oral anticoagulant or low molecular weight 
heparin (LMWH). If receiving warfarin, the patient must have an INR ≤3.0. 
Patients should have no active bleeding (that is, no bleeding within 14 days 

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prior to C1D1) or pathological condition present that carries a high risk of 
bleeding (e.g., tumor involving major vessels or known varices). 
8. Albumin level ≥3.0 g/dL 
9. Life expectancy >12 weeks 
10. Ability to understand the nature of this study, comply with protocol requirements, and 
give written informed consent 
11. Willingness of men and women of reproductive potential to observe conventional and 
effective birth control (consistent with local regulations) for the duration of treatment and 
for 6 months following study completion (or longer as required by local regulations 
including 6 months plus 5 half-lives for female patients in South Korea and 3 months plus 
5 half-lives for male patients in South Korea). Please refer to Appendix A for detailed 
criteria for men and women of reproductive potential. 
4.2. 
Exclusion Criteria (All Parts and Treatment Arms, Unless Noted) 
To be eligible for participation in the study, patients must not meet any of the following exclusion 
criteria: 
1. Have non-adenocarcinoma histologic subtype of gastric/GEJ cancer (e.g., adenosquamous 
carcinoma, squamous carcinoma, etc.) 
2. Have unresolved toxicities from prior anticancer therapy, defined as toxicities (other than 
alopecia) not yet resolved to National Cancer Institute Common Terminology Criteria for 
Adverse Events (NCI-CTCAE) version 5.0, grade ≤1 or baseline. Patients with chronic 
grade 2 toxicities (except for Grade 2 peripheral neuropathy) may be eligible per the 
discretion of the Investigator after discussion and approval from the Sponsor 
3. Have a history of several allergic and/or anaphylactic reactions to known chimeric, human, 
or humanized antibodies, fusion proteins or known allergies to components of EO-3021, 
ramucirumab, or dostarlimab 
4. Have serious concurrent illness or clinically relevant active bacterial, fungal or viral 
infection including but not limited to the following: 
a. Active hepatitis B or C infection (whether or not on active antiviral therapy) 
i. For Arms A3 and B3 (Combination of EO-3021 plus dostarlimab), patients 
must have documented negative Hepatitis B surface antigen (HBsAg) and 
Hepatitis C antibody tests within 3 months prior to C1D1, see Section 4.2.3. 
b. Known human immunodeficiency virus (HIV) infection 
c. Other concurrent infectious disease requiring IV antibiotics within 2 weeks prior to 
C1D1 
Note: testing for HIV or hepatitis B or C is not required unless clinically indicated 
or required by local regulations 
5. Have diagnosis of another malignancy, or history of systemic treatment for invasive cancer 
within last 3 years. Note: Patients with Stage I cancer who have received definitive local 
treatment and are considered unlikely to recur are eligible. Diagnosis of non-melanoma 
skin cancer, carcinoma in situ of the cervix or breast, or noninvasive tumor does not affect 
eligibility. 
6. Have active central nervous system (CNS) disease involvement, defined by cerebrospinal 
fluid (CSF) cytology, magnetic resonance imaging (MRI) or computerized tomography 
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a. Patients with asymptomatic CNS metastases are eligible if they have been clinically 
stable for at least 4 weeks prior to C1D1 and do not require interventions such as 
surgery, radiation, or any corticosteroid therapy for management of symptoms 
related to CNS disease. 
b. Patients with history of brain metastasis previously treated with radiation and/or 
surgical resection and without evidence of progression at screening are eligible, 
including those on stable low-dose of steroids (i.e., 10 mg orally (PO) daily of 
prednisone or equivalent). 
c. Screening for CNS disease is not required. Patients with history of CNS disease 
should have head imaging within the last 3 months documenting no active disease. 
Patients with signs/symptoms concerning for CNS involvement should undergo 
head imaging to rule out active CNS disease at screening. 
7. Have history of non-infectious pneumonitis/interstitial lung disease  
8. Have peripheral neuropathy Grade ≥2 
9. Have active ocular surface disease defined as symptomatic or Grade ≥2 disease involving 
the cornea at baseline (based on screening ophthalmic examination) 
10. Have history of Grade ≥2 gastritis 
11. Are pregnant or breastfeeding   
12. Have previously received anti-CLDN18.2 ADCs or any ADC containing an auristatin 
payload 
13. Have had major surgery (excluding tumor biopsy) within 28 days prior to C1D1 
14. Have received systemic anticancer therapy including chemotherapy, radiotherapy, 
biological therapy, targeted therapy, immunotherapy and investigational therapies within 
28 days or 5 half-lives, whichever is shorter, before the first dose of EO-3021 and the 
combination with ramucirumab or dostarlimab 
a. Use of palliative radiotherapy for bone metastases or local radiotherapy for pain 
relief within 2 weeks before the first dose of EO-3021 and the combination with 
ramucirumab or dostarlimab is allowed. 
b. Ongoing use of drugs for bone metastasis related events (e.g., zoledronic acid) will 
not affect eligibility. 
15. Have history of allogenic hematopoietic stem cell transplantation or solid organ 
transplantation  
16. Use of any drugs or substances known to be strong inducers or inhibitors of CYP3A 
enzymes (Table 9) and/or P-glycoprotein within 7 days prior or 3 half-lives, whichever is 
shorter, before the first dose of EO-3021 and the combination with ramucirumab or 
dostarlimab 
17. Have clinically significant cardiac disease, including but not limited to, any of the 
following within 6 months prior to C1D1: 
a. Myocardial infarction 
b. Unstable angina pectoris 
c. Cerebrovascular accident, transient ischemic attack, cerebral infarction 
d. Uncontrolled congestive heart failure (New York Heart Association Class III or IV) 
e. Uncontrolled or poorly controlled hypertension (defined as >160 mmHg systolic or 
>100 mmHg diastolic for >4 weeks despite standard medical management)  
f. Unstable cardiac arrhythmia requiring acute therapy (including torsades de pointes) 

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g. Prolongation of the QT interval corrected for heart rate (QTcF) > 480 ms on at least 
2 of 3 consecutive electrocardiograms (ECGs) and/or mean QTcF > 480 ms on all 
3 ECGs during screening. Correction of suspected drug induced QTcF prolongation 
may be attempted at the investigator’s discretion if considered clinically safe. 
18. Have received any live vaccine within 30 days of enrollment. Vaccination against 
coronavirus disease 2019 (COVID-19) using vaccines that are authorized via the 
appropriate regulatory mechanisms (e.g., Emergency Use Authorization, Conditional 
Marketing Authorization, or Marketing Authorization Application) are not exclusionary. 
Note: mRNA and adenoviral-based COVID-19 vaccines are considered non-live. If a 
COVID-19 vaccine is administered at any time, the date of COVID-19 vaccination must be 
entered in the eCRF. 
19. Patients who are not appropriate candidates for participation in this clinical study for any 
other reason as deemed by the investigator. 
4.2.1. 
Exclusion Criteria for Part B Expansion (All Treatment Arms B1, B2, B3) 
In addition to the main exclusion criteria, patients must not meet any of the following exclusion 
criteria: 
1. Have HER2+ disease as defined by American Society of Clinical Oncology-College of 
American Pathologists guidelines for gastric/GEJ adenocarcinoma 
2. Have non-measurable disease per RECIST v1.1 
4.2.2. 
Additional Exclusion Criteria for Combination with Ramucirumab (Arms A2 
and B2) 
In addition to the main exclusion criteria, patients must not meet any of the following exclusion 
criteria: 
1. Received prior treatment with ramucirumab and other VEGFR2 inhibitors 
2. Have experienced any Grade 3-4 gastrointestinal bleeding within 3 months prior to C1D1.  
3. Have a history of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other 
significant thromboembolism (venous port or catheter thrombosis or superficial venous 
thrombosis are not considered “significant”) during the 3 months prior to C1D1. 
4. Have cirrhosis at a level of Child-Pugh B (or worse) or cirrhosis (any degree) and with a 
history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis.  
a. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics 
or paracentesis. 
5. Is receiving chronic antiplatelet therapy, including dipyridamole or clopidogrel, or similar 
agents. Once-daily aspirin use (maximum dose 325 mg/day) is permitted. 
6. Have a prior history of GI perforation/fistula (within 6 months of first dose of protocol 
therapy) or risks factors for perforation. 
7. Have a serious or nonhealing wound, ulcer, or bone fracture within 28 days prior to C1D1. 
8. Have a minor surgery/subcutaneous venous access device placement within 7 days prior to 
C1D1. 
9. The patient has elective or planned major surgery to be performed during the course of the 
clinical trial. 

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4.2.3. 
Additional Exclusion Criteria for Combination with Dostarlimab (Arms A3 and 
B3)  
In addition to the main exclusion criteria, patients must not meet any of the following exclusion 
criteria: 
1. Prior treatment with immune checkpoint inhibitors (ICI) including dostarlimab and other 
anti-PD-1, anti-PD-L1, etc. 
2. Have an active autoimmune disease that has required systemic treatment in the past 2 years 
(i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). 
Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement 
therapy for adrenal or pituitary insufficiency) is not considered a form of systemic 
treatment. 
3. Have experienced any of the following with prior immunotherapy: any immune-related 
adverse event ≥Grade 3, immune-mediated severe neurologic events of any grade (e.g., 
myasthenic syndromic/myasthenia gravis, encephalitis, Guillain Barré syndrome, or 
transverse myelitis), exfoliative dermatitis of any grade (Stevens-Johnson syndrome [SJS], 
toxic epidermal necrolysis [TEN], or drug reaction with eosinophilia and systemic 
symptoms [DRESS] syndrome), or myocarditis of any grade. Non-clinically significant 
laboratory abnormalities are not exclusionary. 
4. Have documented presence of HBsAg at Screening or within 3 months prior to C1D1. 
Patients with a negative HBsAg and positive Hepatitis B core antibody result are eligible 
only if HBV DNA is negative.  
5. Have a positive Hepatitis C virus (HCV) antibody test result at Screening visit or within 
3 months prior to C1D1. Note: Patients with a positive HCV antibody test result due to 
prior resolved disease can be enrolled, only if a confirmatory negative HCV RNA test is 
obtained. 
5. 
ENROLLMENT AND REGISTRATION PROCEDURES 
5.1. 
Enrollment of Patients  
The patient must willingly consent after being informed of the procedures to be followed, the 
experimental nature of the treatment, potential benefits, alternatives, side effects, risks, and 
discomforts. Human protection committee (institutional review board [IRB]/ethics committee 
[EC]) approval of this protocol and the ICF is required. Eligible patients who wish to participate 
will be enrolled into the study after fulfilling the eligibility criteria for the study. 
5.2. 
Screen Failures 
Screen failures are patients who do not fulfill the eligibility criteria for the study, and therefore are 
not enrolled into the study. Participating study sites are required to document all screened 
candidates initially considered for inclusion in this study. If a patient is excluded from the study, 
the reasons for exclusion are documented in the patient’s source documents, and on the Screening 
and Enrollment log. Patients who screen fail may be re-screened according to inclusion and 
exclusion criteria after appropriate treatment or observation at the discretion of the Investigator. 
Re-screened subjects are assigned a new screening number and signed a new ICF. Each patient 
has one re-screening opportunity. If a patient re-screens, some study assessments (e.g., baseline 

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imaging, baseline ophthalmic exams, etc.) may not need to be repeated if they originally occurred 
within the appropriate screening window for the new C1D1.  
 
5.3. 
Registration of Patients 
Registration must occur prior to the initiation of protocol therapy (i.e., C1D1). Patient registration 
and dose level assignment are performed by the Sponsor or Clinical Research Organization (CRO) 
designee. The Sponsor or CRO designee documents the patient identification number, dose level, 
and date of enrollment on the Registration Form and sends the completed form back to the site 
following the registration request. 
Sites cannot enroll or administer a dose of EO-3021 (or EO-3021 in combination with 
ramucirumab or dostarlimab) to any patient without receiving the assigned patient number, 
treatment arm and dose cohort (if applicable) from the CRO. The patient should commence 
treatment as soon as practical after receiving the registration confirmation. 
For additional information regarding study registration, please refer to the Study Reference 
Manual. 
5.4. 
Replacement of Patients 
If a patient withdraws or is withdrawn from the study either prior to C1D1, or prior to the 
completion of the DLT observation period in Part A (Dose Escalation) for any reason other than 
DLT and does not meet the minimum requirements for inclusion in the MTD-determining 
population described in Section 6.3.5, that patient may be replaced, if fewer than 3 patients are 
dosed that dose level. 
Any patient receiving at least one dose of EO-3021 will be asked to have all end of treatment safety 
evaluations performed as described in the protocol schedule of assessments (Appendix C). 
5.5. 
Blinding Procedures 
This is an open-label study. No blinding procedures will be applied. 
6. 
STUDY TREATMENT 
All patients entering this study will receive EO-3021 (alone or in combination with ramucirumab 
or dostarlimab) by IV infusion at a dose level based on data evaluation from the prior cohort(s). 
Patients should receive EO-3021 infused over 90-120 (±10) minutes for the first dose in C1D1. In 
the absence of infusion reactions, subsequent infusion time may gradually be decreased to 
60-90 (±10) minutes, as tolerated. Longer infusion times with EO-3021 may be acceptable based 
on patient tolerance and adverse events. Patients in Arms A2 and B2 should receive ramucirumab 
infused over 60 (±10) minutes; subsequent infusion time may gradually be decreased to 
30 (±10) minutes as tolerated by the patient. Patients in Arms A3 and B3 should receive 
dostarlimab infused over 30 (±10) minutes as tolerated by the patient. All doses should be 
administered on an outpatient basis. Patients will receive the protocol therapy until disease 
progression, unacceptable toxicity, or one or more protocol-specific treatment discontinuation 
criteria have been met as described in Section 6.8.1.  

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6.1. 
Selection of Starting Dose of EO-3021 (Monotherapy) 
The proposed starting dose in the clinical study of EO-3021 sponsored by Elevation Oncology is 
1.0 mg/kg IV Q3W. The starting dose is based on the safety, tolerability, and efficacy data obtained 
in the clinical study of SYSA1801-CSP-001 sponsored by CSPC in China.  
The starting dose in the clinical study of SYSA1801-CSP-001 was 0.5 mg/kg IV Q3W, which was 
estimated based on toxic dose levels in Sprague Dawley rat and cynomolgus monkeys, 
toxicokinetic data in animal species, and with consideration of the pharmacological activity 
observed in the efficacy study in mouse models. One patient received EO-3021 at this dose of 
0.5 mg/kg IV Q3W. The patient did not experience a DLT or intolerance during the treatment 
cycles as defined in the study protocol. The patient had a best overall tumor response of SD, and 
discontinued study treatment due to progressive disease (PD) after 5 months of study treatment. 
At the next dose level at 1.0 mg/kg IV Q3W, 3 patients were enrolled and treated under the 3+3 
study design; no DLT was experienced, and only mild/moderate (Grade 1/2) adverse events were 
reported. One patient had a best overall tumor response of confirmed PR and 2 patients with PD. 
Based on the overall benefit/risk of EO-3021, and to limit the number of patients exposed to a 
potentially subtherapeutic dose, the starting dose in the study sponsored by Elevation Oncology is 
set at 1.0 mg/kg IV Q3W. 
As the toxicities of EO-3021 are related mainly to the conjugated small molecule cytotoxin 
MMAE, the starting clinical dose in the study SYSA1801-CSP-001 sponsored by CSPC in China 
was determined using the recommended approaches to setting a first-in-human starting dose for 
small molecule cytotoxic drugs. The guidance provided in the International Conference on 
Harmonisation (ICH) S9 guideline (“Nonclinical Evaluation for Anticancer Pharmaceutical”) 
recommends setting the starting dose at 1/10th the severely toxic dose (STD) in 10% of animals 
(STD10) in rodents or 1/6th the HNSTD in nonrodents according to body surface area (BSA) 
calculation. 
In the 6-week repeat-dose toxicity study in Sprague Dawley rats, there was 4% mortality at 
50 mg/kg EO-3021 (less than STD10); this is equivalent to a human dose of 10.1 mg/kg based on 
BSA conversion. Applying a safety factor of 10 on rodent STD results in a maximum 
recommended starting dose (MRSD) of 1.01 mg/kg. In the 6-week repeat-dose toxicity study in 
cynomolgus monkeys, the HNSTD of EO-3021 was 20 mg/kg. Based on its human equivalent 
dose (HED) of 8.09 mg/kg and a safety factor of 6 based on non-rodent HNSTD, the MRSD was 
calculated to be 1.35 mg/kg. The data from both relevant species suggest a similar starting dose. 
In animal efficacy model studies, the effective doses (single dose in 3-week period) for the 
3 CLDN18.2 overexpressing models were 0.5 mg/kg (0.04 mg/kg HED; NUGC4-CLDN18.2), 
2 mg/kg (0.16 mg/kg HED; BxPC3CLDN18.2), and 4 mg/kg (0.33 mg/kg HED; 
NCI-H460-CLDN18.2). 
6.2. 
Selection of Starting Dose for Combination 
6.2.1. 
EO-3021 
Prior to this amendment, the starting dose in monotherapy dose escalation was 1.0 mg/kg IV Q3W 
as described above. Three patients (2 with gastric/GEJ adenocarcinoma and 1 with pancreatic 
cancer) were treated at 1.0 mg/kg IV Q3W with no DLTs. Doses of up to 2.9 mg/kg IV Q3W have 
been evaluated and are ongoing with a manageable safety profile. No DLTs were observed at 

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2.0 mg/kg IV Q3W and 2.5 mg/kg IV Q3W. DLTs were observed at 2.9 mg/kg IV Q3W. These 
DLTs were Grade 3 encephalopathy and Grade 3 fatigue in patients with pancreatic cancer. In the 
combination dose finding part of the study, the starting dose of EO-3021 will be 2.0 mg/kg IV 
Q3W. The dose can be escalated to 2.5 mg/kg IV Q3W or de-escalated to doses between 2.0 mg/kg 
and 1.0 mg/kg IV Q3W based on the SRC recommendation following standard 3+3 study design. 
6.2.2. 
Ramucirumab 
In gastric/GEJ cancer, the approved dose of ramucirumab is 8 mg/kg every 2 weeks as 
monotherapy and 8 mg/kg on Days 1 and 15 in combination with paclitaxel 80 mg/m2 on Days 1, 
8, 15 of a 28-day cycle. In NSCLC, the approved dose of ramucirumab is 10 mg/kg on Day 1 in 
combination with docetaxel 75 mg/m2 on Day 1 of a 21-day cycle (CYRAMZA, 2022). Based on 
the ramucirumab IB, two dose regimens, 8 mg/kg Q2W and 10 mg/kg Q3W, were selected for the 
8 Phase 3 studies, including gastric cancer (REGARD and RAINBOW), NSCLC (REVEL), 
colorectal cancer (RAISE), hepatocellular carcinoma (REACH and REACH-2), urothelial 
carcinoma (RANGE), and breast cancer (ROSE). The choice of Q2W dosing versus Q3W dosing 
was primarily determined by the regimen of combination therapies. Furthermore, outcomes from 
2 dose-response studies demonstrated that ramucirumab 8 mg/kg Q2W or 10 mg/kg Q3W dosing 
regimens are appropriate for second-line gastric cancer, NSCLC, and colorectal cancer. Given that 
EO-3021 is administered once every 3 weeks, the dose of ramucirumab administered in the 
combination arm will be 10 mg/kg IV Q3W.  
6.2.3. 
Dostarlimab 
The approved dose of dostarlimab as monotherapy for the treatment of dMMR recurrent or 
advanced endometrial cancer and solid tumors is 500 mg IV every 3 week for the first 4 doses then 
1000 mg IV every 6 weeks until disease progression or unacceptable toxicity. The approved dose 
of dostarlimab as combination therapy for the treatment of dMMR/microsatellite instability-high 
(MSI-H) primary or recurrent endometrial cancer is 500 mg IV every 3 weeks with carboplatin 
and paclitaxel for 6 doses then 1000 mg IV monotherapy every 6 weeks until disease progression, 
unacceptable toxicity, or up to 3 years (JEMPERLI, 2024). The transition from Q3W to Q6W 
dosing regimen of dostarlimab reduced the frequency of dosing visits for patients after the initial 
4 or 6 doses. However, given that EO-3021 is dosed Q3W until disease progression, unacceptable 
toxicity, or 1 or more protocol-specific treatment discontinuation criteria have been met, the dosing 
regimen of dostarlimab will be as 500 mg IV Q3W for the duration of study treatment in 
combination with EO-3021. The maximum duration of the combination of dostarlimab and 
EO-3021 is 3 years from the date of therapy start. 
6.3. 
Study Part A:  Dose-Escalation Procedure 
6.3.1. 
Monotherapy Dose-Escalation (Arm A1) 
The study explores a Q3W schedule in which a dose is administered once every 3 weeks.  
Arm A1 (monotherapy dose escalation) follows the BOIN MTD (Yuan 2016, Zhou 2018). The 
starting dose of EO-3021 in Arm A1 (monotherapy) is 1.0 mg/kg IV Q3W with 4 planned dose 
levels (Table 1). Intermediate dose levels or higher dose levels of EO-3021 may be explored, 
depending on the observed safety profile and PK data analysis, if deemed appropriate. 

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Table 1 
Illustrative Dose Escalation of EO-3021 in Arm A1 (Monotherapy) 
Dose Level 
EO-3021 (mg/kg) 
% Increase from Prior Dose Level 
Patients (n) 
1 
1.0 
- 
3-12 
2 
2.0 
100% 
3-12 
3 
2.5 
25% 
3-12 
4 
2.9 
16% 
3-12 
The target toxicity rate for the MTD is 25% and the target sample size in Arm A1 (monotherapy 
dose escalation) is approximately 30. Patients enrolled are treated in cohorts of 3. Dose limiting 
toxicities are defined in Section 6.3.4 and the DLT evaluation period is 21 days. The BOIN design 
uses the following rule, optimized to minimize the probability of incorrect dose assignment, to 
guide dose escalation/de-escalation: 
• if the observed DLT rate at the current dose is ≤0.197, escalate the dose to the next 
higher dose level 
• if the observed DLT rate at the current dose is >0.298, de-escalate the dose to the next 
lower dose level 
• otherwise, stay at the current dose. 
At each dose level, a 3+3 run-in is applied to override the above rules when the number of subjects 
treated at the current dose is 3. Specifically, it will escalate the dose if 0 of 3 DLT, stay at the 
current dose if 1 of 3 DLT, and de-escalate the dose if ≥2 of 3 DLTs. As a result of the incorporation 
of the 3+3 run-in, the updated dose escalation/de-escalation and elimination rules are summarized 
in Table 2, which will be used to conduct the trial. Dose is not escalated to the next higher level 
unless 3 subjects are treated and are DLT evaluable. The dose escalation phase of Arm A1 is 
complete if the sample size reaches approximately 30 or the number of evaluable subjects treated 
at the current dose reaches 12 and the dosing decision according to Table 2 is to stay at the current 
dose. At the discretion of the SRC and Sponsor, additional backfill patients may be included to 
further characterize the MTD/RP2D. Further, the SRC and Sponsor may choose to evaluate two 
candidate RP2Ds in expansion.  
Table 2 
Dose Escalation/De-escalation Rules for the BOIN Design 
# of Evaluable Subjects 
Treated at Current Dose 
1 
2 
3  
4 
5 
6 
7 
8 
9 
10 
11 
12 
Escalate if # of DLT ≤ 
0 
0 
0 
0 
0 
1 
1 
1 
1 
1 
2 
2 
De-escalate if # of DLT ≥ 
1 
1 
2* 
2 
2 
2 
3 
3 
3 
3 
4 
4 
Eliminate if # of DLT ≥ 
N
A 
N
A 
3 
3 
3 
4 
4 
4 
5 
5 
6 
6 
BOIN = Bayesian optimal interval; DLT=dose-limiting toxicity; NA = not evaluable 
Note: “# of DLT” is the number of patients with at least 1 DLT. When none of the actions (i.e., escalate, de-escalate, 
or eliminate) is triggered, stay at the current dose for treating the next cohort of subjects. “NA” means that a dose 
cannot be eliminated before treating 3 evaluable subjects. “*” indicates the 3+3 design run-in. 
When using Table 2, please note the following: 

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• “Eliminate” means eliminate the current and higher doses from the trial to prevent 
treating any future patients at these doses because they are overly toxic. 
• When a dose is eliminated, automatically de-escalate the dose to the next lower level. 
When the lowest dose is eliminated, the study will be terminated or amended.  
• If none of the actions (i.e., escalation, de-escalation, or elimination) is triggered, treat 
the new patients at the current dose. 
• If the current dose is the lowest dose and the rule indicates dose de-escalation, treat the 
new patients at the lowest dose unless the number of DLTs reaches the elimination 
boundary, at which point terminate or amend the study. 
• If the current dose is the highest dose and the rule indicates dose escalation, treat the 
new patients at the highest dose. 
6.3.2. 
Combination Dose-Escalation (Arms A2 and A3) 
The starting dose of EO-3021 in Arm A2 (combination with ramucirumab) and Arm A3 
(combination with dostarlimab) is 2.0 mg/kg IV Q3W and will be escalated to 2.5 mg/kg IV Q3W 
or de-escalated to doses between 2 mg/kg and 1 mg/kg IV Q3W as recommended by the SRC 
following the standard 3+3 design (Table 3). Ramucirumab will be administered as 10 mg/kg IV 
Q3W after EO-3021. Dostarlimab will be administered as 500 mg IV Q3W after EO-3021. 
Table 3: 
Illustrative Dose Escalation of EO-3021 in Arm A2 (combination with 
ramucirumab) and Arm A3 (combination with dostarlimab) 
Dose Level 
EO-3021 (mg/kg) 
% change from starting dose 
Patients (n) 
0 
1.0-2.0* 
Up to 50% decrease 
3-6 
1 
2.0  
Starting dose 
3-6 
2 
2.5 
25% increase 
3-6 
*As recommended by the SRC if de-escalation is needed 
At each dose level within Arm A2 (combination with ramucirumab) and Arm A3 (combination 
with dostarlimab), a standard 3+3 design will be applied. Specifically, the design starts off by 
treating 3 patients at the starting dose. If no DLTs are observed, the study proceeds to the next 
higher dose with 3 more patients. If 1 DLT is observed among the previous 3 patients, 3 more 
patients are treated at the current dose. If 1-2 DLTs are observed among the 3-6 patients, 
respectively, at the starting dose, then the dose of EO-3021 will be de-escalated to a lower dose 
determined by the SRC. If ≥2 DLTs occur in 3 or 6 patients at any level, the previously evaluated 
dose becomes the maximum tolerated dose. Dose escalation continues until an MTD is defined. 
Dose is not escalated to the next higher level unless 3 subjects are treated and are DLT evaluable. 
The dose escalation phase of Arm A2 and Arm A3 is complete if the sample size reaches 
approximately 18 or the number of evaluable subjects treated at the current dose reaches 6 and the 
dosing decision according to Table 3 is to stay at the current dose. At the discretion of the SRC 
and Sponsor, additional backfill patients may be included to further characterize the MTD/RP2D. 
Further, the SRC and Sponsor may choose to evaluate two candidate RP2Ds in expansion.  

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6.3.3. 
Intermediate Dose Levels 
Intermediate dose levels of EO-3021 other than the target doses stipulated in the study schemas 
(Figure 2, Figure 3, and Figure 4), Table 1, and Table 3 may be explored following the 
demonstration of a DLT to ascertain a safe and effective dose(s). Selection of doses will be 
determined by the SRC based on risk/benefit to patients. 
6.3.4. 
Dose-Limiting Toxicity (DLT) 
A TEAE is defined as an adverse event (AE, according to CTCAE Version 5.0) that starts on or 
after the first administration of study medication. 
A DLT is defined as a TEAE that is considered at least possibly related to study treatment, occurs 
within the first 21 days of treatment initiation (i.e., during Cycle 1), meets at least one of the criteria 
listed below (with severity graded according to CTCAE v5.0), and is not reasonably attributed to 
the patient’s underlying disease or another medical condition.    
Patients enrolled to backfill do not contribute to the DLT rate for the determination to 
escalate/de-escalate the dose level.  
Hematological DLT will be defined as:  
• Grade 4 neutropenia (ANC <0.5 x 109/L) present for more than 7 days 
• Febrile neutropenia (defined as ANC <1.0×109/L with a single temperature >38.3°C 
[101°F] or a sustained temperature of ≥38°C [100.4°F] for more than 1 hour) 
• Grade 4 thrombocytopenia (platelets <25 x 109/L)  
• Grade 3 thrombocytopenia (platelets <50 x 109/L) with clinically significant bleeding 
• Grade 4 anemia (life-threatening consequences; urgent intervention indicated) 
Non-hematological DLT will be defined as:  
• Grade 3 or 4 non-hematologic toxicity. The following will not be considered DLTs:  
− Grade 3 nausea and/or vomiting or diarrhea lasting <72 hours with maximal 
supportive therapy 
− Grade 3 fatigue for <7 days 
In addition, the following events are also qualified as DLTs:  
• Grade 3 and above infusion-related reaction  
• Treatment delay of EO-3021 for Cycle 2 Day 1 (C2D1) by >21 days due to unresolved 
treatment related toxicity.  
• Dose reduction of EO-3021 for any reason at C2D1 (e.g., the patient receives a lower 
dose at C2D1 than C1D1) 
• Concurrent elevation of ALT or AST ≥3 × ULN and total bilirubin >2 × ULN (>35% 
direct bilirubin; >3 × ULN total bilirubin for subjects with Gilbert’s syndrome) or ALT 
or AST ≥3 × ULN, which may indicate severe liver injury (potential Hy’s Law), in the 
absence of cholestasis and other causes (e.g., viral hepatitis, other preexisting or acute 

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liver disease, or another drug capable of the observed). Any case where uncertainty 
remains as to whether it represents a potential Hy’s law case should be reviewed with 
the Sponsor Medical Monitor. 
• For patients with hepatic metastases, AST or ALT >8 x ULN or AST or ALT >5 x ULN 
for ≥14 days excluding other causes (e.g., viral hepatitis, other preexisting or acute liver 
disease, or another drug capable of the observed).  
• Any death during DLT-period not clearly due to the underlying disease or extraneous 
causes 
The following non-hematologic TEAEs will not be considered DLTs: 
• Asymptomatic Grade 3 or 4 electrolyte abnormalities or lab abnormalities that are not 
clinically significant per the investigator and resolve spontaneously or with standard 
medical treatment within 72 hours 
6.3.5. 
Determination of Dose-Limiting Toxicities 
The patient population used for determination of DLTs will consist of patients who have received 
the intended dose of EO-3021 and have met the minimum 21-day DLT observation period in 
Part A (Dose Escalation). Toxicity appearing following this minimum observation period may be 
considered a DLT, if clinically relevant. Patients enrolled to backfill do not contribute to the DLT 
rate for the determination to escalate/de-escalate the dose level.    
6.3.6. 
Maximum Tolerated Dose 
The EO-3021 MTD for Arm A1 (monotherapy) will be estimated based on all DLT evaluable 
patients using isotonic regression. The target toxicity rate for the MTD is 25% in Arm A1 based 
on the BOIN design.   
The EO-3021 MTD in combination with ramucirumab (Arm A2) or dostarlimab (Arm A3) is 
defined as the highest dose level of EO-3021 at which no more than 0 of 3 or 1 of 6 patients 
experiences a DLT during the first cycle of therapy. The target toxicity rate for the MTD in 
combination is 33% in Arm A2 (combination with ramucirumab) and Arm A3 (combination with 
dostarlimab) based on the standard 3+3 design.  
6.3.7. 
Recommended Phase 2 Dose 
The RP2D will not be greater than the MTD. However, the RP2D may be a lower dose level in 
certain circumstances: 
• If emerging toxicity at the MTD is unpredictable or undesirable for other reasons 
• If clear evidence of efficacy is noted at lower doses with a cleaner safety profile 
• If longer follow-up on earlier patient cohorts suggests the emergence of delayed 
toxicity  
The SRC will review the totality of the data from dose escalation and recommend one or more 
candidate RP2D for Part B (Expansion). If two candidate RP2Ds are selected for expansion 
simultaneously, randomization may be employed to assign patients to one of two candidate RP2Ds. 

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6.3.8. 
Safety Overview and Dose-Escalation Decisions 
A SRC is established to monitor study conduct and to assess the safety and tolerability and PK (if 
available) of EO-3021. The SRC is composed of Sponsor representatives, site Investigators, and 
CRO representatives. Regular conference calls between participating centers, the designated CRO, 
and the Sponsor will be scheduled bi-weekly during the dose-escalation phase. Additional calls 
may be scheduled at any time if warranted by the emerging safety profile. The purpose of each 
call will be to review patient enrollment and emerging safety data. Participating investigators and 
the Sponsor’s Medical Monitor will review study drug-related toxicities, current patient PK 
profiles if available, and any other relevant data from the current cohort before escalating to the 
next dose. The SRC will provide a recommendation for the RP2D including the potential to 
evaluate intermediate doses, higher doses or more than one RP2D.  Additional information on the 
SRC can be found in the study SRC Charter.  
6.4. 
Study Part B:  Dose-Expansion at the RP2D 
Once the RP2D has been selected for a treatment arm in Part A (e.g. A1, A2, or A3) then the 
treatment arm may proceed to Part B (e.g. B1, B2, or B3). 
A total of approximately 120 patients could be enrolled in Part B (Expansion), including 
approximately 80 patients in Arm B1 (monotherapy) and 20 patients each in Arm B2 (combination 
with ramucirumab) and Arm B3 (combination with dostarlimab). The plan for the expansion group 
may be adjusted based on the enrollment of patients in the dose escalation phase and evolving data.  
Part B (Expansion) will allow the following: 
• Further characterization of the safety and PK profile 
• Confirmation or modification of the ultimate EO-3021 dose to be used in future studies 
• Early exploration of efficacy in relevant patient population 
If two candidate RP2Ds are selected for expansion simultaneously within a treatment arm, 
randomization may occur during Part B (Expansion) to assign patients to one of two candidate 
RP2Ds in each cohort. 
6.5. 
Dose Modifications 
6.5.1. 
Dose Modification Rules 
Dose reductions or treatment delays are allowed as clinically indicated by the treating physician. 
Scheduled prophylaxis for management of nausea/vomiting is recommended for all patients prior 
to C1D1 as outlined in Section 6.5.3. If EO-3021 or combination therapy (e.g., ramucirumab or 
dostarlimab) meets the criteria for dose delay for drug-related AEs regardless of whether the event 
is attributed to E0-3021, ramucirumab, or dostarlimab, then administration of both drugs must be 
delayed if any of the delay criteria are met. Patients whose treatment is delayed due to toxicity 
will either discontinue study treatment or will proceed with the next cycle of treatment when 
toxicity has improved (as long as the toxicity resolves within 21 days or with approval from the 
Sponsor) according to the dose modifications below.  
Any allowed dose modification and any deviation from the intended dose (e.g., missed doses or 
overdoses) should be documented on the dose electronic Case Report Form (eCRF). 

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If the study drug is interrupted for >21 days, the patient has to be rescanned to ensure no disease 
progression has occurred and the Investigator and the Sponsor Medical Monitor agree that 
continued treatment at the same or lower dose is in the best interest of the patient; otherwise 
discontinue the study drug.   
6.5.2. 
Dose Modification Criteria for EO-3021 
Dose modifications may occur during Part A (Dose Escalation) or Part B (Expansion). In Part A 
(Dose Escalation), any patient who was previously enrolled in a dose cohort that was subsequently 
determined to be above the MTD will be allowed to continue to receive EO-3021 at the MTD, if 
deemed medically appropriate by the Investigator and the Sponsor.  
After Cycle 1 in Part A (Dose Escalation), if a dose reduction is recommended, then the dose 
selected should be the last highest dose tested that was considered to be tolerable in prior subjects 
receiving that dose. After Cycle 1 in Part B (Expansion), if a dose reduction is recommended, 
then the first dose reduction should be 25% of the RP2D and the next dose reduction, if needed, 
should be 50% of the RP2D. Up to two dose reductions are allowed.  
In general, the dose modifications described in Table 4 for non-hematologic and Table 5 for 
hematologic toxicities should be applied to the dosing of EO-3021. Toxicities should be managed 
per institutional guidelines, as appropriate, and should include evaluation for all potential 
underlying causes. Appropriate subspeciality consultation should be sought, as clinically 
indicated.  
Management and supportive care guidelines for selected toxicities are outlined in Section 6.5.2.1 
(nausea and/or vomiting), Section 6.5.2.2 (infusion-related reactions), and Section 6.5.2.3 (ocular 
adverse events). 
Table 4: 
Dose Modification Guidelines for Non-Hematologic Toxicities Considered 
Related to Study Treatment 
CTCAE v5.0 Grade Action and Dose Modification for EO-3021b 
Grade 1 
• 
Continue study treatment at current dose level 
• 
Monitor closely 
• 
Provide supportive care according to institutional standards 
Grade 2 
• 
Interrupt study treatment if clinically indicated 
• 
Monitor closely 
• 
Provide supportive care according to institutional standards 
• 
If the toxicity resolves to Grade ≤1 or the patient’s baseline within 21 days, resume 
EO-3021 at current dose level 
• 
If the Grade 2 toxicity recurs, a dose reduction may be considered if medically appropriate
in consultation with the Sponsor Medical Monitor 
• 
If the Grade 2 toxicity does not resolve to Grade ≤1 or the patient’s baseline within 
21 days, consider discontinuation of study treatment or further dose reduction  
Grade 3 (does not 
meet DLT criteria) 
• 
Interrupt study intervention if clinically indicated 
• 
Monitor closely 
• 
Provide supportive care according to institutional standards 
• 
The study treatment may be considered for a dose reduction upon recovery of the toxicity 
to Grade ≤1 or the patient’s baseline within 21 days  
• 
If the Grade 3 toxicity recurs, either permanently discontinue study treatment or, if the 

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CTCAE v5.0 Grade Action and Dose Modification for EO-3021b 
subject is clinically benefiting, consider continuation of study treatment at a further lower
dose in consultation with the Sponsor Medical Monitor 
• 
If the Grade 3 toxicity does not resolve to Grade ≤1 or the patient’s baseline within 21 
days, discontinue study treatment unless the treating physician and the Medical Monitor 
agree that continued treatment at lower doses is in the best interest of the patient 
Grade 3 (meets DLT 
criteriaa) 
• 
Interrupt or discontinue study treatment as deemed medically appropriate 
• 
Monitor closely 
• 
Provide supportive care according to institutional standards 
• 
The study treatment may be considered for a dose reduction upon recovery of the toxicity 
to Grade ≤1 or the patient’s baseline within 21 days, if deemed medically appropriate by 
the investigator and Sponsor Medical Monitor   
• 
If the Grade 3 toxicity recurs, either permanently discontinue study treatment or, if the 
subject is clinically benefiting, consider continuation of study treatment at a further lower
dose in consultation with the Sponsor Medical Monitor 
• 
If the Grade 3 toxicity does not resolve to Grade ≤1 or the patient’s baseline within 21 
days, discontinue study treatment unless the treating physician and the Medical Monitor 
agree that continued treatment at lower doses is in the best interest of the patient 
Grade 4 
• 
Discontinue study treatment  
• 
Monitor closely 
• 
Provide supportive care according to institutional standards 
CTCAE = Common Terminology Criteria for Adverse Events; DLT = dose limiting criteria. 
a  DLT criteria and exceptions are described in Section 6.3.4. 
b Any patients who require a treatment delay of more than 21 days due to treatment-related toxicity will be discontinued from 
study treatment, unless the treating physician and the Medical Monitor agree that continued treatment at lower doses is in the 
best interest of the patient. 
 
Table 5: 
Dose Modification Guidelines Due to Hematologic Toxicities 
Event per CTCAE v5.0 
Action and Dose Modification for EO-3021c 
Neutropenia 
ANC <1.0×109/L  
(Grade 3) 
Hold dose until recovery to ≤Grade 2 (ANC ≥1.0 x 109/L)a 
• If resolved in ≤7 days, then resume without a dose reduction 
• If resolved in >7 days but ≤21 days, then resume dose at a 25% dose 
reduction 
Recurrence of ANC <1.0×109/L 
(Grade 3) 
Hold dose until recovery to ≤Grade 2 (ANC ≥1.0 x 109/L)a 
• If resolved in ≤7 days, then resume dose at a 25% dose reduction 
• If resolved in >7 days but ≤21 days, then resume dose at a 50% dose 
reduction 
ANC <0.5 x 109/L  
(Grade 4) 
Hold dose until recovery to ≤Grade 2 (ANC ≥1.0 x 109/L)a 
• If resolved in ≤7 days without use of G-CSF, then resume dose at a 
25% dose reduction 
• If resolved in >7 days but ≤21 days and/or requires use of G-CSF, 
then resume dose at a 50% dose reduction 
Recurrence of  
ANC <0.5 x 109/L  
(Grade 4) 
Discontinue study treatment 

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Event per CTCAE v5.0 
Action and Dose Modification for EO-3021c 
Thrombocytopenia 
Platelets <50 x 109/L  
(Grade 3) 
 
Hold dose until improvement to platelets ≥75 x 109/La 
• If resolved in ≤7 days, then resume without a dose reductionb 
• If resolved in >7 days but ≤21 days, then resume dose at a 25% dose 
reductionb 
Recurrence of Platelets <50 x 109/L 
(Grade 3) 
Hold dose until improvement to platelets ≥75 x 109/La,b  
• If resolved in ≤7 days, then resume dose at a 25% dose reduction 
• If resolved in >7 days but ≤21 days, then resume dose at a 50% dose 
reduction 
Platelets <25 x 109/L (Grade 4) 
Discontinue study treatment 
Anemia 
Hemoglobin (Hgb) <80 g/L  
(Grade 3) 
 
Hold dose and consider transfusion per institutional standards 
• If recovered to Grade ≤2 or the patient’s baseline without 
transfusion, then resume at a 25% dose reduction. 
• If transfusion is required to recover to Grade ≤2, then resume at a 
50% dose reduction. 
Recurrence of Hgb <80 g/L  
(Grade 3) 
Hold dose and consider transfusion per institutional standards 
• If recovered to Grade ≤2 or the patient’s baseline without 
transfusion, then resume EO-3021 at a further 25% dose reduction 
• If transfusion is required to recover to Grade ≤2, consider 
discontinue study treatment 
Life threatening consequences; 
urgent intervention indicated 
(Grade 4) 
Discontinue study treatment 
ANC = absolute neutrophil count; CTCAE = Common Terminology Criteria for Adverse Events; G-CSF = granulocyte 
colony -stimulating factor; Hgb = hemoglobin 
a Hold EO-3021 treatment; do at least weekly CBC with differential until toxicity resolves (ANC recovery ≥1.0 x 109/L). 
b Re-treatment criteria = platelets ≥75 x 109/L. 
c Any patients who require a treatment delay of more than 21 days due to treatment-related toxicity will be discontinued from 
study treatment, unless the treating physician and the Medical Monitor agree that continued treatment at lower doses is in the 
best interest of the patient. 
6.5.2.1. 
Management of Nausea and/or Vomiting 
Gastrointestinal toxicity of nausea/vomiting was dose limiting with EO-3021 in the first-in-human 
trial of EO-3021 “A Phase 1 Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic 
Characteristics, Immunogenicity and Preliminary Efficacy of SYSA1801 Injection in Patients with 
CLDN18.2-expressing Advanced Solid Tumors" (Protocol No.: SYSA1801-CSP-001) being 
conducted by CSPC in China. Additionally, nausea and vomiting were the most frequently 
observed side effects in clinical trials of investigational agents targeting CLDN18.2 in patients 
with advanced gastric/GEJ and pancreatic adenocarcinoma (Sahin et al., 2018; Tureci et al., 2019). 
Based on nonclinical toxicology studies, the stomach was one of the main toxic target organs, 
which is not surprising given expression of CLD18.2 in normal gastric mucosa. Based on these 
clinical and nonclinical findings, it is recommended that patients receive optimal medical 
management of nausea and vomiting with initiation of treatment with EO-3021. Institutional 
guidelines may exist and should be consulted for recommended treatment; several major oncology 
organizations such as ASCO have also provided comprehensive guidelines for management of 
nausea and vomiting (Hesketh et al., 2020). 

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The recommended treatment regimens for the prevention and management of nausea/vomiting are 
outlined below. Patients may receive the recommended antiemetic treatment prior to EO-3021 
dosing on Day 1 and to cover Days 2-4 of each Cycle starting with C1D1. Additional supportive 
medications as needed (PRN) should also be considered at the discretion of the treating physician. 
The choice of medications should be selected based on patient-centric factors such as response to 
prior antiemetics and include medications of different mechanisms of actions. Premedication for 
nausea/vomiting, which is a treatment before study drug administration, should be documented on 
the dose eCRF as well as any concomitant medications.  
One of the following regimens, based on the ASCO guidelines for antiemetics in oncology 
(Hesketh et al., 2020) are acceptable for the prevention and management of nausea/vomiting in 
patients receiving EO-3021.  
Regimen I: 5-HT3 receptor antagonist + NK1-receptor antagonist + dexamethasone 
Drug class 
Day 1 
Days 2-4 
5-HT3 receptor 
antagonist 
(select one) 
 
 
Palonosetron 0.50 mg oral or 0.25 mg IV 
 
Granisetron 2 mg oral or 1 mg or 0.01 mg/kg IV or 1 
transdermal patch or 10 mg subcutaneous 
 
Tropisetron 5 mg IV/PO  
 
Ondansetron Single 24-mg dose administered by tablets, 
successive oral dissolving tablets, or oral dissolving film 
applications before the start of chemotherapy, or 8mg or 0.15 
mg/kg IV 
 
Dolasetron 100 mg oral ONLY 
 
Tropisetron 5 mg oral or 5 mg IV 
 
Ramosetron 0.3 mg IV 
 
 
N/A 
NK1-receptor 
antagonist 
(select one) 
 
Aprepitant 125 mg PO or 130 mg IV 
 
Fosaprepitant 150 mg IV  
 
Netupitant-palonosetron 300 mg netupitant/0.5 mg palonosetron 
oral in single capsule 
 
Fosnetupitant-palonosetron 235 mg fosnetupitant/0.25 mg 
palonosetron IV 
 
Rolapitant 180 mg PO 
Aprepitant 80 mg PO 
once daily on Days 2-3 
(if aprepitant on Day 1) 
Dexamethasone 
12 mg or 20 mg IV/PO  
8 mg IV/PO once daily 
 
Regimen II. 5-HT3 receptor antagonist + dexamethasone + olanzapine 
Drug class 
Day 1 
Days 2-4 
5-HT3 receptor 
antagonist 
(select one) 
 
Palonosetron 0.50 mg oral or 0.25 mg IV 
 
Granisetron 2 mg oral or 1 mg or 0.01 mg/kg IV or 1 
transdermal patch or 10 mg subcutaneous 
 
Tropisetron 5 mg IV/PO  
 
Ondansetron Single 24-mg dose administered by tablets, 
successive oral dissolving tablets, or oral dissolving film 
applications before the start of chemotherapy, or 8mg or 0.15 
mg/kg IV 
 
Dolasetron 100 mg oral ONLY 
 
Tropisetron 5 mg oral or 5 mg IV 
 
Ramosetron 0.3 mg IV 
 
 
 
N/A 
Dexamethasone 
12 mg or 20 mg IV/PO 
N/A 
Olanzapine 
5 mg or 10 mg, PO, once 
5 mg or 10 mg PO daily 
 

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Regimen III. 5-HT3 receptor antagonist + NK1-receptor antagonist + dexamethasone + olanzapine 
Drug class 
Day 1 
Days 2-4 
5-HT3 receptor 
antagonist  
(select one) 
 
 
Palonosetron 0.50 mg oral or 0.25 mg IV 
 
Granisetron 2 mg oral or 1 mg or 0.01 mg/kg IV or 1 
transdermal patch or 10 mg subcutaneous 
 
Tropisetron 5 mg IV/PO  
 
Ondansetron Single 24-mg dose administered by tablets, 
successive oral dissolving tablets, or oral dissolving film 
applications before the start of chemotherapy, or 8mg or 0.15 
mg/kg IV 
 
Dolasetron 100 mg oral ONLY 
 
Tropisetron 5 mg oral or 5 mg IV 
 
Ramosetron 0.3 mg IV 
 
 
N/A 
NK1-receptor 
antagonist  
(select one) 
 
Aprepitant 125 mg PO or 130 mg IV 
 
Fosaprepitant 150 mg IV  
 
Netupitant-palonosetron 300 mg netupitant/0.5 mg 
palonosetron oral in single capsule 
 
Fosnetupitant-palonosetron 235 mg fosnetupitant/0.25 mg 
palonosetron IV 
Rolapitant 180 mg PO 
Aprepitant 80 mg PO 
once daily on Days 2-3 
(if oral aprepitant on 
Day 1) 
Dexamethasone 
12 mg or 20 mg IV/PO 
8 mg IV/PO once daily 
Olanzapine 
5 mg or 10 mg, PO, once 
5 mg or 10 mg PO daily 
6.5.2.2. 
Management of Infusion-related Reactions 
As with any therapeutic antibodies, there is a possibility of infusion-related reactions and immune 
responses causing allergic or anaphylactic reactions following the administration of EO-3021. 
Patients receiving EO-3021 should be monitored by means of vital signs, physical examination, 
and signs and symptoms of infusion-related reaction including but not limited to: fever, chills, 
nausea, vomiting, headache, cough, dizziness, rash, and/or lower back pain usually of mild to 
moderate severity and may lead to shortness of breath and severe lowering of blood pressure. 
Infusion of EO-3021 will be slowed or interrupted in case of infusion-related reactions and/or 
hypersensitivity. The Investigator will manage infusion reaction-related AEs according to local 
standard procedure. In the absence of local standard procedures, the Investigator should consider 
treatment guidelines and dose reductions for infusion-related reactions shown in Table 6. 

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Table 6: 
Treatment Guidelines and Dose Modifications for Suspected Infusion-related 
Reactions 
Toxicity Grade per CTCAE v5.0 
Action for EO-3021 Dose 
Grade 1 
Mild transient reaction; infusion 
interruption not indicated; 
intervention not indicated 
• 
Consider slowing infusion rate by 50%, or per institutional 
guidelines based on patient tolerance 
• 
Monitor patient every 15 minutes for worsening of condition 
Grade 2 
Therapy or infusion interruption 
indicated but responds promptly to 
symptomatic treatment (e.g., 
antihistamines, NSAIDS, 
narcotics, IV fluids); prophylactic 
medications indicated for ≤24 hrs 
• 
Stop infusion 
• 
Administer diphenhydramine hydrochloride 50 mg IV, 
acetaminophen 500-650 mg orally, and oxygen 
• 
Resume infusion at 50% of the prior rate once infusion reaction has 
resolved, or per institutional guidelines based on patient tolerance 
• 
Monitor patient every 15 minutes for worsening of condition 
• 
For all subsequent infusions, premedicate with dexamethasone 
10 mg orally or IV 
Grade 3 
Prolonged (e.g., not rapidly 
responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms following 
initial improvement; 
hospitalization indicated for 
clinical sequelae 
• 
Stop infusion and disconnect infusion tubing from patient 
• 
Administer diphenhydramine hydrochloride 50 mg IV, 
dexamethasone 10 mg IV, bronchodilators for bronchospasm, and 
other medications or oxygen as medically necessary 
• 
No further treatment with EO-3021 will be permitted 
Grade 4 
Life-threatening consequences; 
urgent intervention indicated 
• 
Stop infusion and disconnect infusion tubing from patient 
• 
Administer epinephrine, bronchodilators, or oxygen as indicated for 
bronchospasm 
• 
Administer diphenhydramine hydrochloride 50 mg IV, 
dexamethasone 10 mg IV 
• 
Consider hospital admission for observation 
• 
No further treatment with EO-3021 will be permitted 
CTCAE = Common Terminology Criteria for Adverse Events; IV = intravenous; NSAIDS = non-steroidal 
anti-inflammatory drugs 
6.5.2.3. 
Management of Ocular Adverse Events 
For monitoring risk of keratopathy, ophthalmic exams including slit lamp examination, optical 
coherence tomography (OCT), and visual acuity, will be performed prior to initiation of drug, 
during treatment and end of treatment. Patients are to be advised to use preservative-free lubricant 
eye drops and avoid contact lenses unless directed by an ophthalmologist.   
Use Table 7 for management of corneal adverse reactions, based on both corneal examination 
findings and changes in best-corrected visual acuity (BCVA): 

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Table 7: 
Dose Reductions for Ocular Adverse Events 
Toxicity Grade per NCI-CTCAE v5.0 
Action for EO-3021 Dose 
Grade 2  
Corneal examination findings: Moderate 
superficial keratopathya  
and/or  
Change in visual acuity: Decline from 
baseline of 3 lines or less or BCVA 20/40 and 
better  
• 
Withhold drug until improvement in both corneal 
examination findings and change in BCVA to Grade 1 or 
better 
• 
Resume at same dose 
• 
If recurrence of Grade 2, resume at reduced dose  
Grade 3 
Corneal examination finding(s): Severe 
superficial keratopathyb  
and/or  
Change in visual acuity: Decline from 
baseline by more than 3 lines or BCVA worse 
than 20/40 up to 20/200 
• 
Withhold drug until improvement in both corneal 
examination findings and change in BCVA to Grade 1 
or better  
• 
Resume at reduced dose (reduce dose by 25%) 
• 
If recurrence of Grade 3, discontinue study treatment   
Grade 4 
Corneal examination finding(s): Corneal 
epithelial defectc  
and/or  
Change in visual acuity: BCVA worse than 
20/200: 
• 
Consider permanent discontinuation of drug. If 
continuing treatment, withhold drug until improvement 
in both corneal examination findings and change in 
BCVA to Grade 1 or better 
• 
Resume at reduced dose (reduce dose by 50%) 
• 
If recurrence of Grade 3 or higher, discontinue study 
treatment 
BCVA = best-corrected visual acuity; NCI-CTCAE = National Cancer Institute Common Terminology Criteria for Adverse 
Events 
a Moderate superficial keratopathy with or without patchy microcyst-like deposits, sub-epithelial haze (peripheral), or 
a new peripheral stromal opacity.  
b Severe superficial keratopathy with or without diffuse microcyst-like deposits, sub-epithelial haze (central), or a new 
central stromal opacity.  
c Corneal epithelial defect such as corneal perforation. 
6.5.3. 
Dose Modification Criteria for Ramucirumab (CYRAMZA) 
Reduce dose, withhold dose, or discontinue ramucirumab (CYRAMZA) to manage adverse 
reactions as described in Table 8. The dose of ramucirumab is 10 mg/kg IV Q3W in combination 
with EO-3021. Ramucirumab may be dose reduced to 8 mg/kg IV Q3W for the first dose reduction 
and to 6 mg/kg IV Q3W if a second dose reduction is needed. Patients must discontinue 
ramucirumab if more than 2 dose reductions are required. The patient may continue to receive 
EO-3021 as monotherapy if, in the Investigator’s and Sponsor’s opinions, the patient may continue 
to derive clinical benefit.  
All dose modifications and the rationale for the dose modification must be documented in the 
eCRF. 
Table 8: 
Dosage Modifications for Ramucirumab (CYRAMZA) 
Adverse Reaction 
Severity 
Dosage Modification 
Hemorrhage 
Grade 3 or 4 
Permanently discontinue CYRAMZA 
Gastrointestinal 
Perforation 
All Grades 
Permanently discontinue CYRAMZA 

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Adverse Reaction 
Severity 
Dosage Modification 
Wound Healing 
Complications 
All Grades 
• 
Withhold CYRAMZA for 28 days prior to 
elective surgery. Resume CYRAMZA no 
sooner than 2 weeks after surgery and until 
adequate wound healing. 
• 
The safety of resumption of CYRAMZA 
after resolution of wound healing 
complications has not been established. 
Hypertension 
Severe hypertension (Grade 3) 
Withhold CYRAMZA until controlled with 
medical management 
Severe hypertension that cannot 
be controlled with 
antihypertensive therapy 
(Grade 3 and/or 4) 
Permanently discontinue CYRAMZA 
Infusion-Related Reaction 
(IRR) 
Grade 1 or 2 IRR 
Reduce the infusion rate of CYRAMZA by 50% 
Grade 3 or 4 IRR 
Permanently discontinue CYRAMZA 
Posterior Reversible 
Encephalopathy 
Syndrome (PRES)  
All Grades 
Permanently discontinue CYRAMZA 
Proteinuria 
 
First occurrence of increased 
urine protein levels greater than 
or equal to 2 g per 24 hours 
• 
Withhold CYRAMZA until urine protein 
level is less than 2 g per 24 hours. 
• 
Resume CYRAMZA at a reduced dose: 
o Reduce 10 mg/kg dose to 8 mg/kg 
Reoccurrence of urine protein 
level greater than 2 g per 
24 hours following initial dose 
reduction 
• 
Withhold CYRAMZA until urine protein 
level is less than 2 g per 24 hours. 
• 
Resume CYRAMZA at a reduced dose: 
o Reduce 8 mg/kg dose to 6 mg/kg 
Urine protein level greater than 
3 g per 24 hours or in the 
setting of nephrotic syndrome 
Permanently discontinue CYRAMZA 
Discontinuation of ramucirumab: 
Any patient who experiences signs of hepatic encephalopathy or other serious signs of liver 
impairment such as hepatorenal syndrome must be permanently discontinued from ramucirumab 
therapy. 
Patients with unresected primary tumors (or local recurrence) who develop Grade 3 and 4 venous 
thromboembolism may also receive anticoagulation and continue ramucirumab therapy provided 
that the tumor does not confer an excessive bleeding risk, in the opinion of the patient’s physician. 
Grade 3 and 4 arterial thromboembolic events, or any PE/DVT occurring or worsening during 
anticoagulant therapy, require permanent discontinuation of ramucirumab therapy. Any venous or 
arterial event leading to discontinuation of ramucirumab therapy will be considered serious and 
should be reported via the serious adverse event (SAE) mechanism. 
The patient will have ramucirumab permanently discontinued if the protein level is >3 g/24 hours, 
if there is a third occurrence of >2 g/24 hours, or if the protein level does not return to <2 g/24 hours 
within 2 weeks. 

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Ramucirumab should be permanently discontinued in the event of a gastrointestinal perforation or 
fistula formation. 
6.5.4. 
Dose Interruption, Delay, or Discontinuation Criteria for Dostarlimab 
(JEMPERLI) 
Dostarlimab dose reductions are not permitted. Dostarlimab Dose Modification and Toxicity 
Management Guidelines for Suspected Drug related Immune-mediated AEs (imAEs) are included 
in Appendix D. Treatment may be interrupted, delayed, or discontinued due to toxicity. The 
maximum duration of the combination of dostarlimab and EO-3021 is 3 years from the date of 
therapy start. If EO-3021 is discontinued, then dostarlimab should also be discontinued. The 
patient may continue to receive EO-3021 as monotherapy if, in the Investigator’s and Sponsor’s 
opinions, the patient may continue to derive clinical benefit.  
Study intervention interruption is defined as stopping the study intervention administration before 
completion of the infusion, including both cases in which the infusion is resumed and completed 
on the same day and cases in which administration is not resumed that day.  
Study intervention delay is defined as withholding study intervention administration for longer 
than the regularly scheduled study intervention dosing interval. Patients with dose delays of 
≥12 weeks or those where events do not return to baseline or Grade ≤1 (see Appendix D), should 
permanently discontinue study intervention unless the investigator and medical monitor agree 
there is strong evidence supporting continued treatment. 
All dose modifications and the rationale for the dose modification must be documented in the 
eCRF. 
Safety management guidelines, including dose modifications algorithms, for ICI related imAE are 
provided in Section 6.5.4.1. 
6.5.4.1. 
Dose Modifications for Immune Checkpoint Inhibitor (ICI) Immune-mediated 
Adverse Events 
An imAE is defined as an AE of any organ that is associated with study intervention exposure, is 
of unknown etiology, and is consistent with an immune-related mechanism. Special attention 
should be paid to AEs that may be suggestive of potential imAEs. Onset of imAEs can occur after 
the first dose, later after several doses have been administered, or several months after the last dose 
of immunotherapy treatment (Ramos-Casals, 2020). 
Organs most frequently affected by ICI imAEs include the endocrine glands, skin, and liver. Less 
frequently affected systems include the GI tract, nervous, cardiovascular, pulmonary, 
musculoskeletal, ocular, and hematologic systems. Lower grade imAEs are usually treated 
symptomatically and do not require dose delays or discontinuation. Higher grade and persistent 
lower grade imAEs typically necessitate interrupting or discontinuing study intervention and 
administration of systemic steroids or other immunosuppressive agents (such as tumor necrosis 
factor [TNF] blockers) if systemic steroids are not effective, or with hormone replacement or anti-
thyroid therapy. 
Early recognition of drug-related imAEs and initiation of treatment are critical in mitigating 
severity and reducing the risk of complications, because the majority of imAEs are reversible with 
the use of steroids and other immune suppressants or therapies (Pardoll, 2012; Weber, 2012). If a 

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drug-related imAE is suspected, the patient should return to the study site as soon as possible 
instead of waiting for their next scheduled visit. Patients who experience a new or worsening imAE 
should be contacted and/or evaluated at the study site more frequently.  A thorough evaluation 
should be conducted to rule out neoplastic, infectious, metabolic, toxin-related, or other etiologies 
before diagnosing a drug-related imAE. Serological, immunological, and histological (i.e., via a 
biopsy) data should be considered to support the diagnosis of an immune-related toxicity. 
Consultation with an appropriate medical specialist should be considered when investigating a 
possible imAE. 
Details relating to specific subtypes of imAEs suspected to be related to ICI administration with 
corresponding dose modification and general management guidelines are presented in Appendix D 
and Appendix E (Liver safety: requirements and guidelines). All AEs are to be graded according 
to NCI-CTCAE v5 (US Department of Health and Human Services, 2017) unless otherwise 
specified.  
Institutional management guidelines, the Society for Immunotherapy of Cancer clinical practice 
guideline on immune checkpoint-inhibitor-related AEs (Naidoo, 2023), the National 
Comprehensive Cancer Network clinical practice guideline for management of imAEs (NCCN, 
2023), the European Society for Medical Oncology clinical practice guideline for management of 
toxicities from immunotherapy (Haanen, 2022) and/or the American Society of Clinical Oncology 
guideline on management of immune-related adverse events in patients treated with ICI therapy 
(ASCO, 2021) may be consulted and used to supplement the algorithms provided below in 
Appendix D.  
6.5.4.1.1. Liver Event Stopping Criteria for Dostarlimab Arm 
Discontinuation of study intervention for abnormal liver tests is required by the investigator when: 
• a patient meets 1 of the conditions outlined in Figure 5 
• a patient has abnormal liver chemistries not meeting protocol-specified stopping rules if 
the investigator believes that it is in best interest of the patient 

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Figure 5: 
Liver Event Study Intervention Stopping Criteria and Liver Event Increased 
Monitoring Criteria with Continued Study Intervention 
 
ALT = alanine aminotransferase; INR = international normalized ratio; SAE = serious adverse event; 
Total bili = total bilirubin; ULN = upper limit of normal 
Refer to Appendix E for required liver safety actions, monitoring, and follow up to assess the 
causality of liver events. 
Patients who do not meet protocol-specified liver event stopping criteria but meet protocol-defined 
increased monitoring criteria may continue to receive study intervention with increased (i.e., 
weekly) liver chemistry monitoring. Refer to Appendix E for details regarding required increased 
monitoring of liver chemistry with continued study intervention. 
In cases where the investigator is directed to discontinue study intervention permanently, these 
instructions are mandatory; some exceptions may be permitted after consultation with the sponsor 
if the dose modification/treatment guidelines differ from the institutional or professional society 
guidance. The medical monitor can be contacted if there are additional questions about 
drug-related imAE management. 
6.6. 
Duration of Therapy 
Patients will receive multiple cycles of EO-3021 (monotherapy), EO-3021 in combination with 
ramucirumab, or EO-3021 in combination with dostarlimab until disease progression, 

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unacceptable toxicity, or criteria for discontinuation of study treatment and/or withdrawal from the 
study are met (Section 6.8.1). The maximum duration of dostarlimab in combination with 
EO-3021 is 3 years from the date of therapy start. 
6.7. 
Concomitant and Prohibited Medications 
Standard supportive medications may be used in accordance with institutional guidelines and 
Investigator discretion. These may include hematopoietic growth factors to treat neutropenia and 
transfusions for thrombocytopenia or anemia in accordance with ASCO Guidelines, anti-emetics, 
anti-diarrheals, antibiotics, antipyretics, and corticosteroids (up to 10 mg per day prednisone or 
equivalent, unless a compelling clinical rationale for a higher dose is articulated by the Investigator 
and approved by the Sponsor’s Medical Monitor; permitted corticosteroid uses include 
topical/cutaneous, ophthalmic, nasal and inhalational steroids, as well as short courses to treat 
asthma, chronic obstructive pulmonary disease, or other non-cancer related conditions). 
Additionally, while participating in the study, patients should use preservative-free lubricant eye 
drops and avoid contact lenses unless directed by an ophthalmologist. 
All concomitant medications, including transfusions of blood products, will be recorded on the 
appropriate page of the case report form. Concomitant therapy (non-investigational products) 
includes any prescription medication, over-the-counter preparation, herbal therapy, or 
radiotherapy used by a patient between the 28 days preceding study treatment initiation and the 
study treatment discontinuation visit. After the End of Treatment Visit, only anti-cancer therapies 
will be collected in addition to survival information.  
The following therapies are not permitted while on study treatment: 
• Other anti-neoplastic therapy, including cytotoxics, targeted agents, endocrine therapy, 
or other antibodies (Excludes use of agents such as zoledronic acid or RANKL for bone 
metastases initiated at least 14 days prior to C1D1) 
• Any other investigational therapy  
6.7.1. 
Concurrent Palliative Radiotherapy and Elective Procedures  
Palliative radiotherapy to specific sites of disease (e.g., bone metastasis) is permitted if considered 
medically necessary by the treating physician and with approval from the Sponsor Medical 
Monitor. Palliative radiotherapy should not be administered on the same week as EO-3021 
treatment and there should be at least 7-14 days before the next dose of EO-3021 (monotherapy or 
combination). In general, target lesions should not be irradiated without discussion with the 
Sponsor and may be reason for the patient to be removed from study for progressive disease. 
Irradiated lesions will be considered not evaluable for response but can still be used to assess 
disease progression. The intensities, number, and dates of doses received for allowed palliative 
radiotherapy should be recorded on the appropriate eCRF.  
Although EO-3021 is not expected to significantly affect wound healing, any unusual findings 
should be recorded as potential AEs. In the event that elective procedures, including surgery, are 
necessary during study participation, EO-3021 (monotherapy or combination) should not be 
administered at least 7-14 days before and after surgery. Ramucirumab, a VEGFR2 antagonist, has 
the potential to adversely affect wound healing; in the event that elective procedures, including 

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surgery, are necessary during study participation, ramucirumab (Arm A2 and Arm B2) should not 
be administered for 28 days before and at least 14 days after surgery (CYRAMZA, 2022). 
6.7.2. 
Prohibited Medications 
MMAE is substrate for CYP3A and P-glycoprotein, therefore, strong inhibitors and strong 
inducers of CYP3A and P-glycoprotein are prohibited on the study. If concomitant use of strong 
CYP3A/P-glycoprotein inhibitors/inducers is unavoidable, consider delaying EO-3021 treatment 
until the strong CYP3A/P-glycoprotein inhibitors/inducers have cleared from circulation 
(approximately 5 elimination half-lives of the inhibitors/inducers) when possible. If a strong 
CYP3A/P-glycoprotein inhibitors/inducers is co-administered and EO-3021 treatment cannot be 
delayed, patients should be closely monitored for adverse reactions. 
Examples of strong CYP3A inhibitors and inducers are included, but not limited, to those provided 
in Table 9. For an expanded list of fruit juices that are strong CYP3A inhibitors, please see Petric 
et al, 2020. 
Table 9: 
Examples of Strong CYP3A Inhibitors and Inducers 
Strong CYP3A Inhibitorsa 
Strong CYP3A Inducersb 
Boceprevir, clarithromycin, cobicistat, danoprevir and 
ritonavir, elvitegravir and ritonavir, fruit juicec (e.g. 
grapefruit, pomegranate, Seville orange), idelalisib, 
indinavir and ritonavir, itraconazole, ketoconazole, 
lopinavir 
and 
ritonavir, 
nefazodone, 
nelfinavir, 
paritaprevir and ritonavir and (ombitasvir and/or 
dasabuvir), posaconazole, ritonavir, saquinavir and 
ritonavir, 
telaprevir, 
tipranavir 
and 
ritonavir, 
telithromycin, troleandomycin, voriconazole 
Apalutamide, carbamazepine, enzalutamide, mitotane, 
phenytoin, rifampin, St. John’s wort 
AUC = area under the concentration time curve, CYP = cytochrome P450 
a 
Strong inhibitors are drugs that increase the AUC of sensitive index substrates ≥5-fold. 
b Strong inducers are drugs that decrease the AUC of sensitive index substrates by ≥80%. 
c 
See Petric et al, 2020 for an expanded list of fruit juices that are strong CYP3A inhibitors. 
Source: US Food and Drug Administration.  Drug Development and Drug Interactions.  Table of Substrates, Inhibitors 
and Inducers. 
6.8. 
Study Termination and Patient Discontinuation 
6.8.1. 
Patient Discontinuation from Study Treatment 
Patients can be discontinued from study treatment for any of the following reasons: 
• Disease progression (as assessed using RECIST v1.1). Note: Patients with disease 
progression per RECIST v1.1 who, in both the Investigator’s and Sponsor’s opinions, 
may continue to derive clinical benefit, and who meet the criteria listed in Section 6.8.2, 
may be allowed to continue treatment with written approval from the Sponsor. 
• Irreversible or intolerable toxicity thought to be related to drug toxicity; 
• Conditions requiring therapeutic intervention(s) not permitted by the protocol; 
• Significant intercurrent illness precluding continued study participation, or the inability 
of the patient to comply with study requirements for any reason; 

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• Patient requests to discontinue treatment (withdrawal of consent) or is lost to follow 
up. This category does not apply if the underlying reason for the patient request in any 
way relates to toxicity or perceived toxicity; 
• Pregnancy. 
Note: In Arm A2 and Arm B2 (combination with ramucirumab) and Arm A3 and B3 (combination 
with dostarlimab), patients must discontinue from study treatment if EO-3021 is discontinued for 
any reason.  
After discontinuation from protocol treatment, patients must be followed for AEs for at least 
28 days from the last dose of study treatment. Every effort should be made to follow patients after 
withdrawal from study; where the cause of study withdrawal relates to drug toxicity, every effort 
should be made to follow the patient until the toxicity has resolved. 
6.8.2. 
Study Treatment Beyond Progression 
As noted in Section 6.8.1, patients with disease progression per RECIST v1.1 who, in the 
Investigator’s and Sponsor’s opinions, may continue to derive clinical benefit, may be eligible to 
continue in the study if they meet the criteria outlined below: 
• absence of clinical symptoms or signs indicating clinically significant disease 
progression; 
• no decline in ECOG performance status; 
• absence of rapid disease progression or threat to vital organs or critical anatomical sites 
(e.g., CNS metastasis, respiratory failure due to tumor compression, spinal cord 
compression) requiring urgent alternative medical intervention; 
• no significant, unacceptable, or irreversible toxicities related to the trial treatment; 
• have written approval of the Sponsor; 
• have signed an ICF agreeing to continue treatment; and 
• no other treatment discontinuation criteria are met. 
Patients must permanently discontinue treatment if subsequent imaging demonstrates further 
disease progression of ≥10% in the target lesions, unequivocal progression in non-target lesions, 
and/or the appearance of new lesions. 
6.8.3. 
Site and Study Termination 
This study may be terminated at the discretion of the Sponsor or any regulatory agency. Any site 
may elect to discontinue patient enrollment or withdraw their participation from the study for any 
reason. In these circumstances, every effort will be made by the site to provide all outstanding data 
for patients previously enrolled. Conditions that may warrant termination of the study include, but 
are not limited to the following: 
• Emergence of an unexpected, serious, or unacceptable risk to the patients in the study. 
• A decision on the part of the Sponsor to suspend or discontinue testing, evaluation, or 
development of the investigational product. 

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In addition, the Investigator or Sponsor has the right to discontinue a site at any time during the 
study for medical or administrative reasons, such as the following: 
• Unsatisfactory enrollment 
• Good Clinical Practice (GCP) noncompliance such as inaccurate or incomplete data 
collection, falsification of records, failure to adhere to the study protocol. 
6.9. 
Accountability of Study Drug 
The investigator and investigational site staff are responsible for maintaining an accurate inventory 
and accounting of study drug. A record of all vials of study drug received and administered is 
maintained on an investigational drug inventory form provided by the Sponsor or an equivalent 
drug inventory form.  The following information will be recorded: 
• Date, quantity, and lot number(s) of study drug received 
• Date, quantity, and lot number(s) of study drug dispensed from the pharmacy per patient 
• Date, quantity, and lot number(s) of study drug administered to each patient 
• Date, quantity, and lot number(s) of study drug destroyed (if prepared and dispensed, but 
not administered for any reason, the study drug may not be returned to inventory) 
• Date, quantity, and lot number(s) of study drug returned to sponsor, if applicable 
Each shipment of study drug contains an invoice describing the amount of drug shipped to the 
investigational site. The information on the invoice is verified against the actual amount received, 
after which the investigator or designee will place the invoice in the investigator’s file. The 
Sponsor’s monitor will reconcile the information on the investigational drug inventory form with 
the actual amount of study drug remaining at each site on a routine basis. At the conclusion of the 
study, the monitor will either package and ship all unused vials of the study drug back to Sponsor 
for destruction or document the destruction, in accordance with local regulations and institutional 
policy. Following use, empty vials of study drug may be destroyed according to local regulatory 
and environmental requirements. A record of any such destruction will be placed in the 
investigator’s file. 
7. 
STUDY ASSESSMENTS AND EVALUATIONS 
7.1. 
Overview 
All patients should visit the study center on the days specified within this protocol. The complete 
Schedule of Assessments for this study are shown in Appendix C. 
7.2. 
Screening Assessments  
After written informed consent is completed, the following information is collected, and 
procedures are performed for each patient during screening. Unless otherwise specified, screening 
procedures are to be completed within 28 days of C1D1. If the date for a screening procedure falls 
out of the specified window, the procedure must be repeated prior to C1D1. 

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• Part B (Expansion) all arms: Prospective central testing of FFPE block or a minimum of 
6 unstained slides of tumor tissue from a biopsy obtained within 6 months of enrollment 
must be available to submit for central review. (Note: If the patient received any CLDN18.2 
directed therapy after the date of the archival biopsy a new biopsy should be performed 
and FFPE block or 6 unstained slides must be available for prospective central review.)   
• Patient inclusion/exclusion criteria review 
• Medical history (including medical/surgical/cancer histories and demographics) 
• Physical examination (comprehensive exam at screening, including body systems: general, 
head, eyes, ears, nose, and throat (HEENT), respiratory, cardiovascular, abdomen, 
extremities, neurologic, and psychiatric) 
• Vital signs including height (at screening only), weight, blood pressure (BP) in seated 
position, heart rate (HR), respiratory rate (RR), temperature, and oxygen saturation (SpO2) 
• ECOG performance status  
• AE assessment (Section 11.3) 
• Concomitant medication review (including any prescription medications, over-the-counter 
preparations, herbal/vitamin supplements used by a patient between the 28 days preceding 
study treatment initiation) 
• Ophthalmic examination, to include OCT, slit lamp examination, and visual acuity exam  
• 12- lead electrocardiogram in ECG (triplicate) after the subject has been supine for at least 
5 minutes 
• Chemistry (Comprehensive metabolic profile [CMP] to include sodium, potassium, 
chloride, blood urea nitrogen [BUN], creatinine, glucose [non-fasting], albumin, total 
protein, calcium, magnesium, phosphorus, uric acid, and LFTs [ALT, AST, total and direct 
bilirubin, alkaline phosphatase]) 
• Complete blood count (CBC) with differential including hemoglobin, hematocrit, platelets, 
white blood counts (WBC) including absolute counts for neutrophils, lymphocytes, and 
monocytes 
• Tumor markers: only in patients with tumors where monitoring of tumor markers is 
clinically relevant (i.e., CA19-9, CEA, etc.) 
• Coagulation profile to include prothrombin time (PT)/INR and aPTT and/or partial 
thromboplastin time (PTT) 
• Urinalysis (reflex with microscopic examination as appropriate)  
o For Arms A2 and B2 (combination with ramucirumab), if urine dipstick or routine 
analysis is ≥2+, a 24-hour urine collection for protein must demonstrate <1000 mg 
of protein in 24 hours to allow participation in Arms A2 and B2) 
• Assessment for HIV or active Hepatitis B or C infection if clinically indicated or required 
by local regulations within 3 months prior to C1D1. 

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o For Arms A3 and B3 (combination with dostarlimab), the presence of HBsAg will 
be assessed. Patients with a negative HBsAg and positive Hepatitis B core antibody 
result are eligible only if HBV DNA is negative. 
• Serum or urine pregnancy test for women of childbearing potential. If urine test is positive 
or cannot be confirmed as negative, a serum test is required 
• Baseline disease assessment by CT with contrast (preferred) or MRI scan [chest, abdomen, 
pelvis is required at a minimum with scans of additional regions (such as of the neck or 
extremities etc.) to be included as appropriate based on presence of disease or symptoms]. 
Scans performed prior to consent, but within 28 days of C1D1, may fulfill the baseline 
disease assessment requirement, provided the same modality will be used for on-study 
assessments.  
• Part A, Dose Escalation: Confirmation of available archival tumor tissue obtained within 
the last 24 months  
• Part A, Dose Escalation:  Fresh tumor tissue biopsy, if determined to be safe by the 
Investigator. A tumor biopsy obtained prior to consent but no more than 3 months prior to 
C1D1 without any intervening treatment between the biopsy and C1D1 may be used to 
fulfill the fresh tumor tissue requirement with Sponsor approval. 
7.3. 
Study Treatment Assessments 
Refer to the Schedule of Assessments for assessment cadence and windows (Appendix C). 
7.3.1. 
Cycle 1 (Days 1, 2, 3, 5, 8, and 15)  
• Review of patient inclusion/exclusion criteria (Day 1 only) 
• Physical examination (comprehensive on C1D1, then problem/symptom focused at C1D8, 
C1D15). Body systems for comprehensive exam should include the following: general, 
HEENT, respiratory, cardiovascular, abdomen, extremities, neurologic, and psychiatric. 
• Vital signs (Days 1, 8, 15) including weight, BP in seated position, HR, RR, temperature, 
and SpO2 
• ECOG performance status (Day 1 only) 
• AE assessment (Section 11.3) 
• Concomitant medication review (including any prescription medications, over-the-counter 
preparations, herbal/vitamin supplements, and transfusions) 
• 12-lead ECG in triplicate after the patient has been supine for at least 5 minutes  
• Chemistry (CMP), including sodium, potassium, chloride, BUN, creatinine, glucose 
(non-fasting), albumin, total protein, calcium, magnesium, phosphorus, uric acid, and LFTs 
(ALT, AST, total and direct bilirubin, alkaline phosphatase) (Days 1, 8, 15 only) 
• CBC with differential including hemoglobin, hematocrit, platelets, WBCs including 
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• Tumor markers: only in patients with tumors where monitoring of tumor markers is 
clinically relevant (Day 1 only) 
• Coagulation profile to include PT/INR and aPTT (and/or PTT) (Day 1 only) 
• Urinalysis (reflex with microscopic examination as appropriate) (Day 1 only) 
o For Arms A2 and B2 (combination with ramucirumab), if urine dipstick or routine 
analysis is ≥2+, a 24-hour urine collection for protein must demonstrate <1000 mg 
of protein in 24 hours to receive ramucirumab) 
• Serum or urine pregnancy test for women of childbearing potential. If urine test is positive 
or cannot be confirmed as negative (Day 1 only) 
• Study treatment (EO-3021 alone or in combination with ramucirumab or dostarlimab) 
administration (Day 1 only)   
• DLT assessment, with a minimum observation period of 21 days from first dose of study 
drug 
• PK assessment (Section 7.7) 
• ADA/neutralizing antibodies (nAb) assessment (Section 7.8) (Day 1 only) 
7.3.2. 
Cycles 2 and Beyond (on Day 1 of every cycle unless otherwise noted) 
• Physical examination (Limited/problem/symptom focused physical examinations to 
include at a minimum HEENT, cardiovascular, respiratory, and abdomen) 
• Vital signs including weight, BP in seated position, HR, RR, temperature, and SpO2 
• ECOG performance status 
• AE assessment (Section 11.3) 
• Concomitant medication review (including any prescription medications, over-the-counter 
preparations, herbal/vitamin supplements, and transfusions) 
• Ophthalmic examination, including slit lamp examination performed at the end of Cycle 2 
and every other cycle thereafter. Additional exams should be guided by specific ocular 
signs and symptoms as clinically indicated. 
• 12-lead electrocardiogram in ECG (triplicate) after the patient has been supine for at least 
5 minutes, collected pre-dose on D1 of each cycle through Cycle 5, then pre-dose D1 of 
every other cycle starting with Cycle 7 
• Chemistry (CMP), including sodium, potassium, chloride, BUN, creatinine, glucose (non-
fasting), albumin, total protein, calcium, magnesium, phosphorus, uric acid, and LFTs 
(ALT, AST, total and direct bilirubin, alkaline phosphatase) 
• CBC with differential including hemoglobin, hematocrit, platelets, WBCs including 
absolute counts for neutrophils, lymphocytes, and monocytes 
• Tumor markers: only in patients with tumors where monitoring of tumor markers is 
clinically relevant (i.e., CA19-9, CEA, etc.) (Day 1 only) 

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• Coagulation profile to include PT/INR and aPTT (or PTT) (Day 1 of every other cycle 
starting with Cycle 3; additional testing may be performed as clinically indicated) 
• Urinalysis (reflex with microscopic examination as appropriate)  
o For Arms A2 and B2 (combination with ramucirumab), if urine dipstick or routine 
analysis is ≥2+, a 24-hour urine collection for protein must demonstrate <1000 mg 
of protein in 24 hours to receive ramucirumab) 
• Serum or urine pregnancy test for women of childbearing potential. If the urine test is 
positive or cannot be confirmed as negative, a serum test is required. 
• Study treatment (EO-3021 alone or in combination with ramucirumab or dostarlimab) 
administration (Day 1 Q3W) 
• PK assessment (Section 7.7) 
• ADA/nAb assessment (Section 7.8) collected pre-dose on Day 1 of every other cycle e.g., 
C1, C3, C5, etc. Ad hoc samples can be collected at the Investigator or Sponsor’s 
discretion.  
• Disease assessment per RECIST v1.1. Scans (CT with contrast or MRI) every 6 weeks 
from C1D1 for the first 12 months. After 12 months, imaging studies will be conducted 
every 12 weeks. Scans should still be performed following the outlined schedule even if 
doses are delayed/interrupted/missed. The same imaging modality should be used 
throughout the study. 
7.4. 
End of Treatment Visit (within 28 ±3 Days of Last Dose) 
Patients are permitted to continue study treatment (EO-3021 alone or in combination with 
ramucirumab or dostarlimab) until disease progression, unacceptable toxicity, or other 
discontinuation criteria are met (Section 6.8.1). The maximum duration of dostarlimab in 
combination with EO-3021 is 3 years from the date of therapy start. 
If treatment is discontinued because of toxicity or for any other reason(s) at a scheduled treatment 
visit and no study treatment is administered, that visit may fulfill the End-of-Treatment (EOT) 
Visit.  
After withdrawal from or completion of protocol treatment, patients must be followed for 
AEs/SAEs for 28 days after the last dose of study treatment or initiation of the next anti-cancer 
treatment, whichever occurs first. After this period, investigators are only required to report 
AEs/SAEs that they become aware of and are thought to be possibility related to study treatment. 
The following end-of-treatment visit procedures will be performed: 
• Physical examination (comprehensive exam including body systems: general, HEENT, 
respiratory, cardiovascular, abdomen, extremities, neurologic, and psychiatric) 
• Vital signs including weight, BP in seated position, HR, RR, temperature, and SpO2 
• ECOG performance status  
• AE assessment (Section 11.3)  

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• Concomitant medication review (including any prescription medications, over-the-counter 
preparations, herbal/vitamin supplements, and transfusions) 
• Ophthalmic examination, including OCT, slit lamp examination, and visual acuity exam 
• 12-lead Electrocardiogram in ECG (triplicate) after the patient has been supine for at least 
5 minutes 
• Chemistry (CMP), including sodium, potassium, chloride, BUN, creatinine, glucose (non-
fasting), albumin, total protein, calcium, magnesium, phosphorus, uric acid, and LFTs 
(ALT, AST, total and direct bilirubin, alkaline phosphatase) 
• CBC with differential including hemoglobin, hematocrit, platelets, WBCs including 
absolute counts for neutrophils, lymphocytes, and monocytes 
• Tumor markers: only in patients with tumors where monitoring of tumor markers is 
clinically relevant (i.e., CA19-9, CEA, etc.)  
• Coagulation profile to include PT/INR and aPTT (and/or PTT)   
• Urinalysis (reflex with microscopic examination as appropriate)  
• Serum or urine pregnancy test for women of childbearing potential. If the urine test is 
positive or cannot be confirmed as negative, a serum test is required. 
• Optional fresh tumor tissue biopsy, if determined to be safe by the Investigator  
• PK assessment (Section 7.7) 
• ADA/nAb assessment (Section 7.7) 
• Disease assessment by CT with contrast or MRI scan. If a patient discontinues study 
treatment for reasons other than disease progression (e.g., due to toxicities) tumor 
assessments with imaging will continue until initiation of next anti-cancer therapy, death, 
or withdrawal of consent, whichever occurs first. 
7.5. 
Long-term Follow-up (Every 3 Months ±28 Days from Last Treatment) 
Once off study treatment, survival data will be collected via written communication 
(e.g., telephone, email, electronic medical record) or clinic visits every 3 months (±28 days) from 
the date of last treatment until death, loss to follow-up, withdrawal of consent, or study termination 
by the Sponsor. Survival follow-up should include collection of any new anti-cancer therapies and 
procedures taken after the EOT visit. Patients who discontinue study treatment for reasons other 
than disease progression including due to toxicities will continue to receive tumor assessments 
until initiation of next anti-cancer therapy, death, or withdrawal of consent, whichever occurs first. 
Attempts should be made to obtain any death information available via public records. 
7.6. 
Correlative Studies 
Prospective documentation of CLDN18.2 is not a requirement for participation in the dose 
escalation arms. The expression level of CLDN18.2 will be determined retrospectively using an 
IHC assay in a central laboratory and analyzed for the ability to predict or correlate with tumor 
response to EO-3021 as monotherapy and in combination. Enrolling tumors with a broad range of 

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CLDN18.2 expression will support correlative analysis of clinical outcomes with varying 
CLDN18.2 expression in order to potentially establish a more defined cut-off that is clinically 
meaningful to predict and enrich for efficacy.  
As the data around CLDN18.2 as a predictive biomarker for EO-3021 monotherapy matures, the 
Sponsor plans to implement a prospective CLDN18.2 biomarker selection strategy to identify and 
enroll patients who would derive the greater benefit from EO-3021 as monotherapy or in 
combination with ramucirumab or dostarlimab in the expansion arms.   
For patients with tumors where monitoring of tumor markers is clinically relevant (i.e., CA19-9, 
CEA, etc.) tumor marker values will be collected in the eCRF. Baseline PD-L1 status will be 
collected in the eCRF. 
Remaining tumor tissue after conducting the above studies may be used by the Sponsor for further 
analysis of other biomarkers that may be mechanistically linked to EO-3021 activity and 
resistance. At the time of informed consent, patients will be able to refuse storage of these 
remaining samples. 
Directions for processing and shipping the samples are outlined in the Laboratory Manual.  
7.7. 
Pharmacokinetic and ADA Assessments 
The plasma PK parameters (including Cmax, AUC0-t, AUC0-inf, Tmax, t1/2, etc.) of EO-3021, total 
antibody (including EO-3021, i.e., the intact ADC and dissociated antibody), and free MMAE, as 
well as the development of ADA following administration will be assessed by analysis of blood 
samples. For ADA positive samples, further determination of neutralizing activity (i.e., 
measurement of neutralizing antibodies, nAb) will be considered based on the results of the study. 
PK and ADA/nAb samples are to be collected, handled, and processed in accordance with the 
instructions provided in the Laboratory Manual. Blood samples should be collected at prescribed 
time points and the actual sampling time recorded in the eCRF. 
Unscheduled samples for assessment of PK and/or ADA/nAb may be drawn at any time during 
the study at the Investigator or Sponsor’s discretion. 
7.8. 
Adverse Events of Special Interest 
Relevant Information regarding the Adverse Events of Special Interest (AESIs) specified below 
for the EO-3021 clinical program regardless of seriousness will be collected through the targeted 
questionnaires built within the applicable eCRF in the clinical study database. All AESIs should 
be reported within 24 hours following the SAE reporting guidelines.  
Ocular adverse events 
Ocular adverse events including corneal epitheliopathy, keratopathy and keratitis is considered to 
be an important potential risk based on nonclinical data, literature, and available safety information 
for drugs of similar class (e.g., ADCs). While the target antigen, CLDN18.2, has not been reported 
to be expressed in normal ocular tissues, off-target toxicity can result from exposure of ocular 
tissues to the MMAE payload. EO-3021 is produced using a highly selective and site-directed 
conjugation technique, and the concentration of free MMAE toxin component in blood is very 
low, at picogram levels. The mechanism leading to ocular adverse events caused by this product 
needs further study. In the repeat-dose toxicity study of EO-3021 and MMAE in rats, the eye was 

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evaluated as a target organ for toxicity. Single cell necrosis/increased mitotic figures in the cornea 
were observed in the EO-3021 rats treated at ≥10 mg/kg. These microscopic findings were not 
observed in the MMAE small molecule treatment group; however, eye discharge was observed in 
one of the moribund animals. Referring to the experience of marketed products, the clinical study 
of EO-3021 specifies in the study protocol: ophthalmological examination should be performed 
regularly; prophylactic use of preservative-free eye drops with the effects of ocular lubrication and 
protection is recommended from the first dose through the entire period of the study medication. 
After an ocular adverse event occurs, symptomatic treatment should be performed according to 
the advice of the ophthalmologist, ophthalmic examinations should be performed regularly, and 
EO-3021 should be temporarily discontinued until improvement or recovery according to the 
intensity. 
Interstitial lung disease/pneumonitis 
Interstitial lung disease (ILD)/pneumonitis is considered to be an important potential risk based on 
literature and available safety information for drugs of similar class (e.g., ADCs). Expression of 
the target antigen, CLDN18.2, is restricted to normal gastric mucosa. EO-3021 was purposely 
designed to specifically target CLDN18.2 and not CLDN18.1, the expression of the latter can be 
found in normal lung tissue. Nevertheless, ILD/pneumonitis should be ruled out if a patient 
develops an acute onset of new or worsening pulmonary or other related signs/symptoms such as 
dyspnea, cough, or fever. If ILD/pneumonitis is suspected, treatment with EO-3021 should be 
interrupted pending further evaluation. Evaluations should include high resolution CT, 
pulmonologist consultation, pulmonary function tests and pulse oximetry (SpO2), arterial blood 
gases if clinically indicated, and one blood sample collection for PK and exploratory biomarker 
analysis as soon as ILD/pneumonitis is suspected, if feasible. As soon as ILD/pneumonitis is 
suspected, corticosteroid treatment should be started promptly as per clinical treatment guidelines 
(Kubo et al., 2013). 
8. 
RESPONSE EVALUATIONS AND MEASUREMENTS 
Response and progression will be evaluated in this study using RECIST v1.1 as outlined in 
Appendix B. 
Appropriate imaging studies are conducted every 6 weeks ±7 days for the first 12 months. After 
12 months, imaging studies are conducted every 12 weeks (±7 days). Patients who discontinue 
study treatment for reasons other than disease progression including due to toxicities will continue 
to receive tumor assessments following the outlined schedule until initiation of next anti-cancer 
therapy, death, or withdrawal of consent, whichever occurs first. Scans should still be performed 
following the outlined schedule even if doses are delayed/interrupted/missed. The same imaging 
modality should be used throughout the study. Confirmation of response (by repeat scans after 4 
weeks) is required for trials in which response rate is the primary endpoint. 

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9. 
DRUG FORMULATION, AVAILABILITY, ADMINISTRATION, 
AND TOXICITY INFORMATION 
9.1. 
Study Treatments 
Investigational Product 
Dosage Form and Strength 
Manufacturer 
EO-3021 Infusion 
Solution for Infusion / 10.0 mg/mL 
CSPC Megalith 
Biopharmaceutical Co., Ltd. 
Ramucirumab Infusion 
Solution for Infusion / 10.0 mg/mL 
Eli Lilly and Company 
Dostarlimab 
Solution for Infusion / 50.0 mg/mL 
GlaxoSmithKline LLC 
9.1.1. 
Labelling, Packaging, and Supply 
EO-3021 Solution for Infusion is supplied to the pharmacy at the clinical trial site by the CRO in 
vials (of 7.5 mL each vial contains 75 mg EO-3021 drug substance). The immediate packaging 
will contain a statement to conform with FDA Investigational New Drug (IND) requirements as 
follows:  Caution:  New Drug - Limited by Federal (or US) law to investigational use. The batch 
number of the study drug dispensed to the patient should be entered on the eCRF, if applicable. 
Storage conditions for EO-3021 are included on the investigational product label and in the 
Pharmacy Manual.  
Eli Lilly and Company is providing the sponsor commercially labeled drug product vials: 
CYRAMZA® (ramucirumab) injection, for intravenous use. GlaxoSmithKline is providing the 
sponsor dostarlimab-gxly drug product in the form of unlabeled vials.  
Ramucirumab and dostarlimab will be supplied to the pharmacy at the clinical trial site by the 
CRO and should be stored, prepared, and administered per the label (CYRAMZA, 2022 and 
JEMPERLI, 2024; respectively). Refer to the Pharmacy Manual for information regarding 
packaging and labeling. 
All study drugs must be kept in a secure place under appropriate storage conditions. 
9.1.2. 
Preparation and Administration of Study Treatment 
The Investigator (or designee) is responsible for accountability of all used and unused study drug 
supplies at the site. All study drug inventories must be made available for inspection by the 
Sponsor or its representatives and regulatory agency inspectors upon request. 
All CRO Drug Accountability Record Form(s) will be completed by the site and sent to the CRO 
Regulatory Department. Study drug supplies must not be destroyed unless prior approval has been 
granted by the Sponsor or its representative. Please contact the CRO regarding disposal of any 
study drug. 
9.1.2.1. 
EO-3021 
Administration of EO-3021 may require multiple vials, all of which should originate from the same 
lot number. Any vials or preparations are for single use only. Visually inspect the drug product 
before preparation. Discard the vial if visible particles are observed. Based on the calculated 
amount needed for the given dose, EO-3021 drug product is withdrawn from the vial under aseptic 
conditions and diluted in 0.9% sodium chloride injection solution to obtain a solution in the range 
of 0.3-2.0 mg/mL in an infusion bag. Further instructions are provided in the Pharmacy Manual.  

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EO-3021 is administered by IV infusion once every 21 days (±3 days). Patients should receive 
EO-3021 infused over 90 to 120 (±10) minutes for the first dose in C1D1. In the absence of infusion 
reactions, subsequent infusion time may gradually be decreased to 60 to 90 (±10) minutes, as 
tolerated. EO-3021 should not be administered as a bolus or a push. 
9.1.2.2. 
Ramucirumab 
Administration of CYRAMZA (ramucirumab) may require multiple vials, all of which should 
originate from the same lot number. Any vials or preparations are for single use only. Visually 
inspect the drug product before preparation for particulate matter or discoloration. Discard the vial 
if visible particles or discolorations are identified. Based on the calculated amount needed for the 
given dose, CYRAMZA (ramucirumab) is withdrawn from the vial under aseptic conditions and 
diluted in 0.9% sodium chloride injection solution in an intravenous infusion container to a final 
volume of 250 mL. Do not use dextrose containing solutions. Further instructions are provided in 
the Pharmacy Manual.  
Ramucirumab is administered by IV infusion once every 21 days (±3 days). Patients should receive 
ramucirumab infused over 60 (±10) minutes, subsequent infusion time may gradually be decreased 
to 30 (±10) minutes as tolerated by the patient. Ramucirumab should not be administered as a 
bolus or a push. Flush the line with sterile 0.9% sodium chloride injection solution at the end of 
the infusion. 
9.1.2.3. 
Dostarlimab 
Administration of JEMPERLI (dostarlimab) may require multiple vials, all of which should 
originate from the same lot number. Any vials or preparations are for single use only. Visually 
inspect the drug product before preparation for particulate matter or discoloration. The solution is 
clear to slightly opalescent, colorless to yellow. Discard the vial if solution discoloration or visible 
particles are observed. Based on the calculated amount needed for the given dose, JEMPERLI 
(dostarlimab) is withdrawn from the vial under aseptic conditions and diluted in 0.9% sodium 
chloride injection solution to obtain a solution with a final concentration between 2.0-10.0 mg/mL 
in an infusion bag. Further instructions are provided in the Pharmacy Manual.  
Dostarlimab is administered by IV infusion once every 21 days (±3 days). Patients should receive 
dostarlimab infused over 30 (±10) minutes. Dostarlimab should not be administered as a bolus or 
a push. 
10. 
STATISTICAL CONSIDERATIONS 
10.1. 
General Considerations 
The statistical analyses for this study will be descriptive. Data collected will be presented using 
summary tables, figures, and individual patient data listings. For continuous variables, descriptive 
summaries will include the mean, median, standard deviation, the first and third quartiles, 
minimum, and maximum. For categorical variables, the number and percentage of patients in each 
category will be presented.  
In general, all analyses will be presented by study part (Part A or Part B), Arm (e.g. A1, A2, B1, 
etc.) and by dose levels in Part A or by randomized arm in Arm B1. Pooled safety analyses across 

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phase and dose will also be performed for all patients treated by EO-3021 monotherapy, EO-3021 
in combination with ramucirumab, EO-3021 in combination with dostarlimab, and potentially all 
EO-3021 treated patients as appropriate.  
A statistical analysis plan (SAP) will be prepared and finalized before database lock. This 
document will provide further details regarding the definition of analysis variables and analysis 
methodology, including methods to handle missing data, and to address all study objectives. 
10.2. 
Analysis Populations 
• Safety Analysis Population includes all patients receiving at least one dose of study 
treatment.  
• DLT Evaluable Population includes all patients who receive at least one dose of EO-3021 
and complete the DLT observation period or experience DLT(s) within the DLT 
observation period.   
• Efficacy Evaluable Population includes all patients who receive at least one dose of 
EO-3021, have baseline measurable disease and at least one post baseline imaging 
assessment. 
• PK Analysis Population will include all patients in the Safety Analysis Population who 
have at least one evaluable PK assessment. 
• ADA Analysis Population will include all patients in the Safety Analysis Population who 
have at least one valid ADA result.  
Each analysis population may be further grouped by study part, arm, by dose in Part A (Dose 
Escalation), and by arm in Arm B1. 
10.3. 
Determination of Sample Size 
10.3.1. 
Dose Escalation (Part A) 
The sample size during Part A (Dose Escalation) will follow the BOIN design for Arm A1 
(monotherapy) and traditional 3+3 design for Arm A2 (combination with ramucirumab) and Arm 
A3 (combination with dostarlimab). Approximately 70 patients are expected (approximately 
30 patients in Arm A1, 20 patients in Arm A2, and 20 patients in Arm A3). The actual sample size 
(including backfills) will depend on the number of DLTs observed and the number of doses 
explored.  
10.3.2. 
Expansion (Part B) 
For the Part B (Expansion), approximately 120 patients will be treated at the RP2D, including 
approximately 80 patients in Arm B1 (monotherapy) and 20 patients each in Arm B2 (combination 
with ramucirumab) and Arm B3 (combination with dostarlimab).  
For Arm B1, the sample size is not powered based on hypothesis testing between the 2 randomized 
arms. It is based on practical considerations to enable the dose selection for future trials based on 
the totality of data involving efficacy, safety, and tolerability. With 40 patients per arm, the 95% 
exact Clopper-Pearson confidence intervals for ORR are calculated for the various assumed 
response rates (Table 10).  

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Table 10: 
ORR and 95% Confidence Intervals Based on N=40 or 20 
ORR (95% CI) N=40 
ORR (95% CI) N=20 
10% (3%, 24%) 
10% (1%, 32%) 
20% (9%, 36%) 
20 % (6%, 44%) 
30% (17%, 47%) 
30% (12%, 54%) 
40% (25%, 57%) 
40% (19%, 64%) 
50% (34%, 66%) 
50 % (27%, 73%) 
CI = confidence interval; ORR = objective response rate 
For Arms B2 and B3, 20 patients are planned for each cohort. With 20 patients per cohort, the 95% 
exact Clopper-Pearson confidence intervals for ORR are calculated for the various assumed 
response rates (Table 10). 
10.4. 
Analysis Methods 
10.4.1. 
Disposition 
The number and percent of patients who have consented, treated, discontinued (including reasons 
for discontinuation), and completed the study will be summarized. The number of patients for each 
analysis population defined in Section 10.2 will be tabulated. 
10.4.2. 
Demographics and Baseline Characteristics 
Summary statistics will be provided for demographic variables (age, sex, race, ethnicity) and 
baseline disease characteristics (e.g., ECOG performance status). Relevant biomarker, medical 
history, and prior anti-cancer treatments will also be summarized. 
10.4.3. 
Efficacy Analysis 
The primary analysis for efficacy will be based on the Efficacy Evaluable Population in Part B 
(Expansion) by Arm and by Arm (Arm B1 only). Sensitivity analysis may be performed based on 
the Full Analysis Population if it is sufficiently different from the Efficacy Evaluable Population. 
In addition, patients in Part A (Dose Escalation) with the same type of disease and receiving the 
same dose as in Part B (Expansion) may be pooled into the expansion cohort in Part B (Expansion) 
for a sensitivity analysis.   
Best Overall Response (BOR) will be summarized based on the response assessments from all 
visits (scheduled or unscheduled) for each patient. The BOR is defined as the best response per 
RECIST v1.1 in the order of CR, PR, SD, PD, non-evaluable (NE).  A patient will be considered 
as NE for response per RECIST v1.1 at a protocol specified time point if no imaging/measurement 
is done or only a subset of lesion measurements is made. Confirmation scans per RECIST v1.1 
must be done at least 28 days after the initial response. SD measurements must have met the SD 
criteria at least once after study entry at a minimum interval of 35 days. 
Overall Response Rate is defined as the proportion of patients with measurable disease at baseline 
who achieve a CR or PR (confirmed CR or a PR) per RECIST v1.1. The estimate of ORR will be 
accompanied by the Clopper-Pearson 95% confidence intervals (CIs).  
Duration of Response (DOR) is defined as the time from the first occurrence of a response (CR or 
PR) until the date of PD per RECIST v1.1 or death, whichever is earlier. It is calculated among 

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responders (confirmed CR or PR). The Kaplan-Meier methodology will be used to estimate DOR. 
Patients who continue to respond at the time of the analysis will be censored at the last assessment 
of response. The median DOR, if estimable, and the 95% CI will be provided. The proportion of 
patients continuing to respond at 3 months and 6 months from the date of the first response and 
the 95% CI will be provided.  
Disease Control Rate (DCR) is defined as the proportion of patients with measurable disease at 
baseline who achieve a CR, PR, or SD per RECIST v1.1. DCR will be analyzed similarly as the 
ORR.  
Progression-free Survival (PFS) is measured from the date of first study treatment dose (or from 
the date of randomization in Arm B1) until the first date when PD is objectively documented per 
RECIST v1.1 or death from any cause, whichever is earlier. Patients without PD or death will be 
censored at the last available tumor assessment. Details of the PFS and DOR censoring rule will 
be specified in the SAP. PFS will be analyzed using the Kaplan-Meier methodology. The median 
PFS, if estimable, and the 95% CI will be provided. The proportion of patients who are 
progression-free at landmark times (e.g., 3 months, 6 months) from the date of the first dose and 
the 95% CI will be provided.  
Overall survival is measured from the date of first study treatment dose (or from the date of 
randomization in Arm B1) until death. Patients who are alive will be censored at the last known 
alive date. OS will be analyzed similarly as the PFS using the Kaplan-Meier methodology. 
10.4.4. 
Safety Analysis 
Safety analyses will be based on the Safety Analysis Population. Patient incidence of all TEAEs, 
SAEs, and treatment-related AEs will be tabulated by SOC and preferred term per Medical 
Dictionary for Regulatory Activities (MedDRA). All AEs are graded according to NCI-CTCAE 
Version 5.0. AEs by worst grade and AEs leading to treatment discontinuation will also be 
summarized. Other safety endpoints including laboratory results, vital signs, and ECG findings 
will be summarized for all patients in the Safety Analysis Population. 
Concomitant medications will be coded using the World Health Organization-Drug Dictionary and 
they will be listed and summarized by dose level. 
In Part A (Dose Escalation), DLTs, if any, will be summarized based on the DLT analysis set. At 
the end of Part A (Dose Escalation), isotonic regression will be used to estimate the MTD. 
Duration of study treatment, number of doses administered, cumulative amount of dose, and 
relative dose intensity will be summarized by each study drug (EO-3021, ramucirumab, 
dostarlimab). For the combination treatment, the total duration of all study treatment will also be 
calculated. In addition, any modifications to the planned dose including treatment discontinuation 
will be summarized along with the corresponding reasons for each study drug.  
10.4.5. 
Pharmacokinetics 
Plasma concentrations of EO-3021 will be used to calculate the PK parameters. Parameters 
evaluated will include plasma concentration-time profiles and Cmax, Tmax, AUC(0-∞), AUC(0-τ), and 
t1/2 etc. Besides EO-3021, total antibody (including EO-3021, i.e., the intact ADC and dissociated 
antibody), and free MMAE will be analyzed. Evaluation of ADA and nAb levels in appropriate 
patients will also be presented. These parameters will be listed by individual patient and 

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summarized by descriptive statistics (means, medians, ranges, standard deviations, and coefficient 
of variation as appropriate, by treatment group/cohort).  
If potential interactions are suspected, plasma concentrations of ramicurimab or dostarlimab may 
be evaluated. 
Additional details will be provided in a separate PK/ADA analysis plan. 
10.5. 
Planned Analyses 
10.5.1. 
Final Analysis 
The final analysis of the study will occur when either: 
• The last patient completes treatment with a minimum of 12-month follow up, or 
• 3 years following the enrollment of the first patient 
10.5.2. 
Interim Analysis 
In Part A, analyses will be performed for dose escalation/de-escalation decisions at each dose level 
within each Arm (A1, A2, and A3) per the study design.  
In Arm B1, an interim futility analysis will be performed after 20 patients have been randomized 
in the biomarker-selected population in each arm. A Bayesian futility assessment based on a 
beta-binomial model will be used in each arm. The prior distribution is assumed to be a beta 
distribution, beta (0.5, 0.5). If the posterior probability is at least 70% that the ORR is less than 
15% in an arm, it may be considered futile to continue the arm. Specifically, if 2 or less patients 
respond at the interim, the futility boundary is crossed. No formal interim analysis is planned in 
Arm B2 or Arm B3. However, the Bayesian framework will be considered as a monitoring tool. 
The details will be specified in the SAP and the SRC charter.  
Unplanned interim analysis for regulatory interaction or publication purposes may be performed. 
10.6. 
Stopping Rules 
In Part A (Dose Escalation), DLTs will be monitored to guide the dose escalation/de-escalation 
decisions following the BOIN design per Table 2 in Section 6.3. Regular safety reviews will be 
conducted by the Sponsor’s SRC following the SRC charter. 
During Part B (Expansion), evaluations of all Grade 4 or higher treatment-related adverse events 
(TRAE) rate will be conducted to assess if the unacceptable toxicity threshold has been reached. 
If this threshold is met (i.e., TRAE Grade 4 >20%), enrollment to expansion will be halted 
pending review of safety data. 
In Arm B1, an interim futility analysis will be performed after 20 patients have been randomized 
in each arm. Specifically, if 2 or less patients respond at the interim, the futility boundary is 
crossed.  
The study will enroll patients with advanced/metastatic gastric/GEJ adenocarcinoma or advanced 
solid tumors that are likely to express CLDN18.2. Expression of CLDN18.2 is not a requirement 
for enrollment into the study; however, the number of patients with tumors that do not expression 

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CLDN18.2 (e.g., no tumor cells show staining of CLDN18.2 by IHC) and objective responses 
will be assessed periodically to determine benefit/risk. 
After reviewing the cumulative data, the SRC may recommend one of the following actions: 
• Terminate the study 
• Amend the protocol to potentially improve the benefit/risk for patients (e.g., increase 
safety monitoring, modify dose/schedule, mandate premedication, biomarker selection, 
etc.) 
• Continue dose expansion without any changes 
11. 
SAFETY REPORTING AND ASSESSMENT 
Safety assessments will consist of monitoring and recording protocol-defined AEs and SAEs, 
measurement of protocol-specified hematology, clinical chemistry, and UA variables, 
measurement of protocol-specified vital signs, and other protocol-specified tests that are deemed 
critical to the safety evaluation of the study drug. Adverse events will be coded using the latest 
MedDRA dictionary. Severity will be graded according to the NCI-CTCAE Version 5.0. 
The Investigator is responsible for recognizing and reporting AEs to the CRO Safety Department. 
It is the Sponsor’s responsibility to ensure the reporting of relevant SAEs to the applicable local, 
national, or international regulatory bodies. In addition, Investigators must report SAEs and 
follow-up information to their responsible IRB/EC according to the policies of that IRB/EC. 
The Investigator is also responsible for ensuring that every staff member involved in the study is 
familiar with the content of this section. 
11.1. 
Definitions 
11.1.1. 
Adverse Events 
An AE is any untoward medical occurrence in a patient or clinical investigation participant 
administered a pharmaceutical product and does not necessarily have to have a causal relationship 
with this treatment. An AE can therebefore be any unfavorable and unintended sign (e.g., an 
abnormal laboratory finding), symptom, or disease temporarily associated with the use of a drug, 
without any judgement about causality. An AE can arise with any use of the drug (e.g., off-label 
use, use in combination with another drug) and with any route of administration, formulation, dose 
or including overdose. 
11.1.2. 
Serious Adverse Event 
A SAE is any untoward medical occurrence at any dose that: 
• Results in death 
• Is life-threatening  
• Requires inpatient hospitalization of at least 24-hours or prolongation of existing 
hospitalization 

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o For the purpose of this protocol, any hospital admission will be considered an 
inpatient hospitalization, regardless of duration. An emergency room visit without 
hospital admission will not be recorded as a SAE under this criterion, nor will 
hospitalizations for a procedure scheduled before study enrollment (first dose of 
study drug) or elective procedures schedule during the study. However, unexpected 
complications that occur during elective surgery should be recorded as AEs and 
assessed for seriousness. 
• Results in persistent or significant incapacity or disruption of the ability to conduct normal 
life functions 
• Is a congenital anomaly/birth defect 
• Is an important medical event that may not result in death, be life-threatening, or require 
hospitalization, but may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient or subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition.  
o Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse. 
It is important to distinguish between “serious” and “severe” AE, as the terms are not synonymous. 
Severity is a measure of intensity; however, an AE of severe intensity need not necessarily be 
considered serious. Seriousness serves as the guide for defining regulatory reporting obligations. 
“Serious” is a regulatory definition and is based on patient/event outcome or action usually 
associated with events that pose a threat to a patient’s life or vital functions. For example, nausea 
that persists for several hours may be considered severe nausea but may not be considered an SAE. 
On the other hand, a stroke which results in only a limited degree of disability may be considered 
only a mild stroke but would be considered an SAE. Severity and seriousness should be 
independently assessed when recording AEs on the eCRF screen and SAEs on the SAE Report 
Form. 
All SAEs occurring from the time that written informed consent has been obtained through the 
EOT Follow-up Visit (within 28 days after the last dose of study drug administration or initiation 
of alternative anticancer treatment, whichever occurs first) must be reported to the Sponsor CRO 
within 24 hours of the knowledge of the occurrence. After informed consent, but prior to initiation 
of study treatment, only SAEs caused by a protocol-mandated intervention will be collected (e.g., 
SAEs related to invasive procedures such as biopsies). Additionally, all SAEs that the Investigator 
considers possibility related to study drug occurring after the 28-day follow-up period must be 
reported to the Sponsor. 
An event attributed to disease progression must be reported as an SAE if it meets any of the SAE 
reporting criteria listed in this section. If death due to disease progression occurs within 28 days 
after the last dose of study drug, the event term should be listed as “malignant neoplasm 
progression” with the outcome of death. 

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11.1.3. 
Adverse Event of Special Interest 
An adverse event of special interest (AESI) (serious or non-serious) is one of scientific and medical 
concern specific to the sponsor's product or program, for which ongoing monitoring and rapid 
communication by the investigator to the sponsor could be appropriate. 
11.1.4. 
Recording and Reporting of Adverse Events 
Recording of Adverse Events 
All AEs of any patient during the course of the research study will be recorded in the eCRF, and 
the Investigator will give his or her opinion as to the relationship of the AE to the study drug 
treatment (i.e., whether the event is related or unrelated to study drug administration). 
All AEs should be documented. A description of the event, including its date of onset and 
resolution, whether it constitutes a SAE or not, any action taken (e.g., changes to study treatment), 
and outcome, should be provided, along with the Investigator’s assessment of causality (i.e., the 
relationship to the study treatment). For an AE to be a suspected treatment-related event there 
should be at least a reasonable possibility of a causal relationship between the protocol treatment 
and the AE. AEs will be graded according to the NCI-CTCAE v5.0, and changes will be 
documented. 
Wherever possible, constellation of symptoms representing a recognized syndrome will be 
collected uniquely and will not be recorded as the separate component symptoms. For example, a 
patient displaying “flu like symptoms” will have the AE “flu like symptoms” reported but will not 
have each symptom listed. In this example, the symptoms of pyrexia/fever/asthenia/myalgia would 
not be reported individually. 
If the AE is serious, it should be reported immediately to the nominated CRO Safety Department. 
Other untoward events occurring in the framework of a clinical study are to be recorded as AEs 
(i.e., AEs that occur prior to assignment of study treatment that are related to a protocol-mandated 
intervention, including invasive procedures such as biopsies, medication washout, or no treatment 
run-in). 
Any clinically significant signs and symptoms, changes in physical examination, hypersensitivity, 
and other measurements that occur will be reported as AEs and recorded on the relevant eCRF 
screen. Laboratory data will be separately graded, coded, and analyzed according to the 
NCI-CTCAE system. The consistent grading of laboratory data in this manner provides a greater 
level of transparency to abnormalities and renders reporting of laboratory anomalies as AEs 
duplicative and redundant. 
Test findings will be reported as an AE if the test result requires an adjustment in the study drug(s) 
or discontinuation of treatment; and/or test findings require additional testing or surgical 
intervention; a test result or finding is associated with accompanying symptoms; or a test result is 
considered to be an AE by the Investigator. 
Reporting Period for Adverse Events 
All AEs regardless of seriousness or relationship to EO-3021, ramucirumab, or dostarlimab 
treatment (called study treatment), spanning from the start of study treatment, until 28 days after 
discontinuation or completion of study treatment or initiation of alternative anticancer treatment, 
whichever occurs first, as defined by the study for that patient, are to be recorded on the 

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corresponding screen(s) included in the eCRF. After informed consent, but prior to initiation of 
study treatment, only SAEs caused by a protocol-mandated intervention will be collected (e.g., 
SAEs related to invasive procedures such as biopsies). 
All AEs resulting in discontinuation from the study should be followed until resolution or 
stabilization. All new AEs occurring during this period must be reported and followed until 
resolution unless, in the opinion of the Investigator, the AE or laboratory abnormality/ies are not 
likely to improve because of the underlying disease. In this case, the Investigators must record his 
or her reasoning for this decision in the patient’s medical record and as a comment on the eCRF 
screen.  
After 28 days of completion of protocol-specific treatment or discontinuation, only AEs, SAEs, or 
deaths assessed by the Investigator as treatment related are to be reported. 
11.1.5. 
Assessment of Adverse Events 
All AEs and SAEs whether volunteered by the patient, discovered by study personnel during 
questioning, or detected through physical examination, laboratory test, or other means will be 
reported appropriately. Each reported AE or SAE will be described by its duration (i.e., start and 
end dates), regulatory seriousness criteria if applicable, suspected relationship to the study drug 
(see following guidance), and actions taken. 
To ensure consistency of AE and SAE causality assessments, Investigators should apply the 
following general guideline: 
RELATED:  There is a plausible temporal relationship between the onset of the AE and 
administration of the study medication (EO-3021, ramucirumab, or dostarlimab), and the AE 
cannot be readily explained by the patient’s clinical state, intercurrent illness, or concomitant 
therapies; and/or the AE follows a known pattern of response to the study drug; and/or the AE 
abates or resolves upon discontinuation of the study drug or dose reduction and, if applicable, 
reappears upon re-challenge. 
UNRELATED:  Evidence exists that the AE has an etiology other than the study drug(s) 
(e.g., pre-existing medical condition, underlying disease, intercurrent illness, or concomitant 
medication); and/or the AE has no plausible temporal relationship to study drug administration 
(e.g., cancer diagnosed two days after first dose of study drug). 
11.2. 
Serious Adverse Event Reporting by Investigators 
AEs classified by the treating Investigator as serious require expeditious handling and reporting to 
the Sponsor in order to comply with regulatory requirements. Determination of life-threatening or 
serious is based on the opinion of either the Sponsor or the Investigator.  
Serious AEs may occur at any time from consent through 28 days following the last dose of study 
drug or initiation of alternative anticancer treatment, whichever occurs first. and must be reported 
to the Sponsor as SAEs in the EDC system and followed until resolution (with autopsy report if 
applicable). After informed consent, but prior to initiation of study treatment, only SAEs caused 
by a protocol-mandated intervention will be collected (e.g., SAEs related to invasive procedures 
such as biopsies). Additionally, all SAEs that the Investigator considers possibility related to study 
drug occurring after the 28-day follow-up period must be reported to the Sponsor. The Sponsor 

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must be notified of all SAEs, regardless of causality, within 24 hours of the first knowledge 
of the event by the treating physician or research personnel. 
To report an SAE, complete the SAE form electronically in the EDC system for the study. When 
the form is completed, Medpace Safety personnel will be notified electronically and will retrieve 
the form. If the event meets serious criteria and it is not possible to access the internet, send an 
email to Medpace Safety at medpace-safetynotification@medpace.com or call the Medpace SAE 
hotline (phone number listed below), and fax the completed paper SAE form to Medpace (fax 
number below) within 24 hours of awareness. When the EDC system becomes available, the SAE 
information must be entered within 24 hours of the system becoming available. Transmission of 
the SAE report should be confirmed by the site personnel submitting the report. 
Safety Contact Information: 
Medpace Clinical Safety 
Medpace SAE Hotline 
 
Telephone: +1-800-730-5779, dial “3” or +1-513-579-9911, dial “3” 
Fax: +1-866-336-5320 or +1-513-579-0444 
Email: medpace-safetynotification@medpace.com 
 
Follow-up information for SAEs and information on nonserious AEs that become serious should 
also be reported to the CRO Safety Department as soon as it is available; these reports should be 
submitted using the CRO SAE Report Form. The detailed SAE reporting process will be provided 
to the sites in the SAE reporting guidelines contained in the study reference manual. 
Investigators must report SAEs and follow-up information to their responsible IRB according to 
the policies of the responsible IRB. 
11.3. 
Recording of Adverse Events and Serious Adverse Events 
Monitoring for and recording of AEs and SAEs is conducted throughout the study and 28 days 
after the last dose of study treatment or initiation of alternative anticancer treatment, whichever 
occurs first. After this period, investigators are only required to report AE and SAEs that they 
become aware of them and are thought to be related to EO-3021. After informed consent, but prior 
to initiation of study treatment, only SAEs caused by a protocol-mandated intervention will be 
collected (e.g., SAEs related to invasive procedures such as biopsies). All SAEs should be reported 
to the Sponsor or designee within 24 hours of investigator awareness. 
11.3.1. 
Diagnosis Versus Signs and Symptoms 
All AEs should be recorded individually in the patient’s own words (verbatim) unless, in the 
opinion of the Investigator or designated physician, the AEs constitute components of a recognized 
condition, disease, or syndrome. In the latter case, the condition, disease, or syndrome should be 
named rather than each individual sign or symptom. If a constellation of signs and/or symptoms 
cannot be medically characterized as a single diagnosis or syndrome at the time of reporting, each 
individual event should be recorded as an AE or SAE as appropriate on the relevant form(s) (SAE 
Report Form and/or eCRF). If a diagnosis is subsequently established, it should be reported as 

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follow-up information is available. If a diagnosis is determined subsequent to the reporting of the 
constellation of symptoms, the signs/symptoms should be updated to reflect the diagnosis.  
Progression of malignancy (including fatal outcomes) in and of itself, if documented by use of 
appropriate method (e.g., as per RECIST v1.1 for solid tumors), should not be reported as an SAE. 
An event attributed to disease progression must be reported as an SAE if it meets any of the SAE 
reporting criteria listed in Section 11.1.2 (e.g., hospitalization). If death due to disease progression 
occurs within 28 days after the last dose of study drug, the event term should be listed as 
“malignant neoplasm progression” with the outcome of death. 
11.3.2. 
Persistent or Recurrent Adverse Events 
A persistent AE is one that extends continuously, without resolution, between patient evaluation 
timepoints. Such events should only be recorded once on the SAE Report Form and/or the AE 
eCRF screen. If a persistent AE becomes more severe or lessens in severity, it should be recorded 
on a separate SAE Report Form and/or AE eCRF screen. 
A recurrent AE is one that occurs and resolves between patient evaluation timepoints, and 
subsequently recurs. All recurrent AEs should be recorded on an SAE Report Form and/or AE 
eCRF screen. 
11.3.3. 
Deaths 
Deaths that occur during the protocol-specified AE reporting period that are assessed by the 
Investigator solely attributable to progression of disease will be recorded on the “Study 
Discontinuation” eCRF screen. All other on-study deaths, regardless of attribution, will be 
recorded on an SAE Report Form and expeditiously reported to the CRO Safety Department. 
When recording a SAE with an outcome of death, the event or condition that caused or contributed 
to the fatal outcome should be recorded as the single medical concept on the SAE Report Form 
and AE screen of the eCRF. If the cause of death is unknown and cannot be ascertained at the time 
of reporting, record “Death NOS” on the eCRF Adverse Event screen. During poststudy survival 
follow-up, deaths attributed to progression of disease will be recorded only on the “After 
Progressive Disease Follow-Up” eCRF screen. 
11.3.4. 
Hospitalization, Prolonged Hospitalization, or Surgery 
Any AE that results in hospitalization of >24 hours or prolongation of pre-existing hospitalization 
should be documented and reported as an SAE unless specifically instructed otherwise in this 
protocol. There are some hospitalizations that do not require reporting as an SAE. 
Treatment within or admission to the following facilities are not considered to meet the criteria of 
“inpatient hospitalization” (although if any other SAE criteria are met, the event must still be 
treated as an SAE and immediately reported): 
• Emergency Department or Emergency Room 
• Outpatient or same-day surgery units 
• Observation or short-stay unit 
• Rehabilitation facility 

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• Hospice or skilled nursing facility 
• Nursing homes, Custodial care or Respite care facility 
Hospitalization during the study for a preplanned surgical or medical procedure (one that was 
planned prior to entry in the study) does not require reporting as a SAE to the CRO Safety 
Department. 
11.3.5. 
Pre-Existing Medical Conditions 
A pre-existing medical condition is one that is present at the start of the study. Such conditions 
should be recorded on the General Medical History of the eCRF screen. A pre-existing medical 
condition should be recorded as an AE or SAE only if the frequency, severity, or character of the 
condition worsens during the study. When recording such events on an SAE Report Form and/or 
AE eCRF screen, it is important to convey the concept that the pre-existing condition has changed 
by including applicable descriptors. 
11.3.6. 
New Cancers 
The development of a new primary cancer should be regarded as an AE and will generally meet at 
least 1 of the seriousness criteria (Section 11.1.2). New primary cancers are those that are not the 
primary reason for the administration of the study treatment and have developed after the inclusion 
of the patient into the study. They do not include metastases of the original cancer. Symptoms of 
metastasis or the metastasis itself should not be reported as an AE/SAE, as they are considered to 
be disease progression. 
11.3.7. 
Pregnancy, Abortion, Birth Defects/Congenital Anomalies 
If the patient or partner of a patient participating in the study becomes pregnant while on study, 
the Investigator should report the pregnancy to the Sponsor’s clinical safety representative within 
24 hours of being notified. The Sponsor’s safety representative will then forward the Pregnancy 
form to the Investigator for completion as outlined in the Study Manual.  
A patient becoming pregnant while on study drug will immediately be withdrawn from the study 
and early termination study procedures will be performed. The investigator should inform the 
patient of the risks of continuing with the pregnancy and the possible effects on the fetus. 
Monitoring of the patient should continue until conclusion of the pregnancy. At the completion of 
the pregnancy, the investigator will document the outcome of the pregnancy. The Sponsor will 
collect information on the outcome of the pregnancy. If the outcome of the pregnancy meets the 
criteria for immediate classification as an SAE (i.e., postpartum complication, spontaneous 
abortion, stillbirth, neonatal death, or congenital anomaly), the investigator should follow the 
procedures for reporting an SAE. 
In the event of a pregnancy occurring in the partner of a male patient participating in the study, the 
pregnant partner should be requested to report the pregnancy to the investigator, who in turn should 
report it to the Sponsor. The partner should also be informed of the risks of continuing with the 
pregnancy, and the possible effects on the fetus. 
Congenital anomalies/birth defects always meet SAE criteria, and should therefore be 
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Pregnancy Form should also have been previously completed and will need to be updated to reflect 
the outcome of the pregnancy. 
11.3.8. 
Adverse Events of Special Interest (AESIs) 
Adverse events of ocular toxicities (e.g., corneal epitheliopathy, keratopathy, keratitis) and 
ILD/pneumonitis are required to be reported as AESIs within 24 hours of knowledge of the event 
to the sponsor representative as an SAE using the eCRF. The investigator should then use clinical 
judgment to establish the cause based on local standard of care and follow the subject by 
conducting testing as clinically indicated.  
11.3.9. 
EO-3021 Overdose 
Symptomatic and non-symptomatic overdose must be reported in the eCRF system. Any accidental 
or intentional overdose with the study treatment, even if not fulfilling a seriousness criterion, is to 
be reported to the CRO Safety Department no greater than 24 hours from first knowledge of the 
event using the corresponding screens in the eCRF and following the same process described for 
SAE reporting. For definition purposes, a drug overdose is considered to be a dose of study drug 
that is greater than 15% over the theoretical protocol specified dose for the patient considering any 
toxicities that may have warranted dose reduction. 
For information on how to manage an overdose of EO-3021, see the IB. 
12. 
QUALITY ASSURANCE AND QUALITY CONTROL 
12.1. 
Monitoring 
Site monitoring shall be conducted to ensure that patient protection, study procedures, laboratory, 
study intervention administration, and data collection processes are of high quality and meet 
Sponsor, GCP/ICH and, when appropriate, regulatory guidelines. Overall study monitoring will 
be conducted through a combination of on-site visit and centralized monitoring. A clinical monitor 
will make regularly scheduled trips to the investigational site to review the progress of the study, 
study data and site processes. At each visit, the monitor will review various aspects of the study 
including, but not limited to: screening and enrollment logs; compliance with the protocol and 
study manuals and with the principles of GCP; completion of CRFs; source data verification; study 
drug accountability and storage; facilities and staff. 
The actual frequency of monitoring trips will depend on the enrollment rate and performance at 
each site. The investigator will allow Elevation Oncology, and/or its representatives or designees, 
access to all pertinent medical records, as required by federal regulations, in order to allow for the 
verification of all data gathered in the eCRFs and for the review of the data collection process. 
During scheduled monitoring visits, the investigator and the investigational site staff must be 
available to meet with the study monitor in order to discuss the progress of the study, make 
necessary corrections to CRF entries, respond to data clarification requests and respond to any 
other study-related inquiries of the monitor. In addition to on-site monitoring visits, the Sponsor 
and/or representatives will also be routinely reviewing data. Any queries identified through this 
review will be managed within the systems established for query resolution and tracking. Inquiries 
related to study conduct which require further information or action will be discussed within the 

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study team for appropriate and documented escalation plans. It is expected that response to data 
clarification requests and other study-related inquiries will occur throughout the course of the study 
through regular communication with the site monitor, the Sponsor or representatives, and 
review/entry of data into the electronic study database. 
In accordance with Health Insurance Portability and Accountability Act (HIPAA) and associated 
privacy regulations, a patient’s authorization to use personal identifiable health information may 
be required from each patient before commencement of research activities. This authorization 
document must clearly specify what parties will have access to a patient’s personal health 
information, for what purpose and for what duration. 
12.2. 
Audits and Inspections 
At any time during the course of the study, representatives of the FDA and/or other regulatory 
agencies may review the conduct or results of the study at the investigational site. The Investigator 
will permit study-related quality audits and inspections by the Sponsor or its representative(s), 
government regulatory authorities, and the IRB/EC of all study-related documents (e.g., source 
documents, regulatory documents, data collection instruments, CRFs). The Investigator will 
ensure the capability for review of applicable study-related facilities. The Investigator will ensure 
that the auditor or inspector or any other compliance or quality assurance reviewer is given access 
to all study-related documents and study-related facilities. 
The investigator must promptly inform Elevation Oncology of any audit requests by health 
authorities and will provide Elevation Oncology with the results of any such audits and with copies 
of any regulatory documents related to such audits. 
13. 
ETHICAL, FINANCIAL, AND REGULATORY 
CONSIDERATIONS 
This research study will be conducted according to the standards of GCP outlined in the ICH R2 
Tripartite Guideline and Code of Federal Regulations (CFR) Title 21 Part 312, applicable 
government regulations, institutional research policies and procedures and any other local 
applicable regulatory requirement(s). 
13.1. 
Institutional Review Board Approval 
The clinical study protocol, ICF, patient information sheet (PIS), IB, available safety information, 
patient documents (e.g., study diary), patient recruitment procedures (e.g., advertisements), 
information about payments (i.e., Investigator payments) and compensation available to the 
patients and documentation evidencing the PI’s qualifications should be submitted to the IRB/EC 
for ethical review and approval if required by local regulations, prior to the study start. 
The PI/Sponsor and/or designee will follow all necessary regulations to ensure appropriate, initial, 
and on-going, IRB/EC study review. The PI/Sponsor (as appropriate) must submit and, where 
necessary, obtain approval from the IRB/EC for all subsequent protocol amendments and changes 
to the informed consent document. Investigators will be advised by the Sponsor or designee 
whether an amendment is considered substantial or non-substantial and whether it requires 
submission for approval or notification only to an IRB/EC. 

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Safety updates for EO-3021, will be prepared by the Sponsor or its representative as required, for 
distribution to the Investigator(s) and submission to the relevant IRB/EC. 
The study will not be initiated until there is approval of the protocol, informed consent document 
and any other material used to inform the patient about the nature of the study by the local IRB or 
EC. The IRB or EC should be duly constituted according to local regulatory requirements. 
Approval must be in the form of a letter signed by the Chairperson of the IRB/EC or the 
Chairperson’s designee, must be on IRB/EC stationery and must include the protocol by name 
and/or by designated number. If an investigator is a member of the IRB/EC, the approval letter 
must stipulate that the Investigator did not participate in the final vote, although the investigator 
may participate in the discussion of the study. The investigator will also inform the IRB/EC of any 
SAE that the Sponsor reports to regulatory authorities, will report on the progress of the study at 
least yearly (or more frequently if required by local regulation or guidance) and will provide to the 
IRB/EC a final summary of the results of the study at the conclusion of the study. 
13.2. 
Regulatory Approval 
As required by local regulations, the Sponsor will ensure all legal aspects are covered, and approval 
of the appropriate regulatory bodies obtained, prior to study initiation. If required, the Sponsor will 
also ensure that the implementation of substantial amendments to the protocol and other relevant 
study documents happen only after approval by the relevant regulatory authorities. 
13.3. 
Informed Consent 
No study related procedures will be performed until a patient or a patient’s legal representative has 
given written informed consent. The Sponsor will provide to the investigator a sample informed 
consent document that includes all the requirements for informed consent according to the ICH 
GCP, U.S. FDA guidelines (21 CFR 50) and/or local regulatory guidelines. However, it is up to 
the investigator to provide a final informed consent that may include additional elements required 
by the investigator’s institution. Changes to the Sponsor’s sample informed consent should receive 
approval from the Sponsor or the Sponsor’s representative prior to use in the study. The informed 
consent document must clearly describe the potential risks and benefits of the study, and each 
prospective participant must be given adequate time to discuss the study with the Investigator or 
site staff and to decide whether or not to participate. Each patient who agrees to participate in the 
study and who signs the ICF will be given a copy of the signed, dated, and witnessed document. 
The provision of informed consent must be documented in the medical record. 
The ICF will be submitted for approval to the IRB that is responsible for review and approval of 
the study. Each consent form must include all of the relevant elements currently required by the 
FDA, as well as local county authority or state regulations and national requirements. 
If an amendment to the protocol substantially alters the study design or the potential risks to the 
patient, the patient’s consent to continue participation in the study should be obtained. 
13.4. 
Confidentiality 
13.4.1. 
Patient Confidentiality 
It is the responsibility of the investigator to ensure that the confidentiality of all patients 
participating in the study and all of their medical information is maintained. Case report forms, 

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and other documents submitted to the Sponsor must never contain the name of a study patient. All 
patients in the study will be identified by a unique identifier which will be used on all eCRFs and 
any other material submitted to the Sponsor. This information, together with the patient’s date of 
birth, will be used in the database for patient identification. All CRFs, and any identifying 
information must be kept in a secure location with access limited to the study staff directly 
participating in the study. Patients will be informed of their rights within the ICF/PIS. 
Confidentiality of patient’s personal data will be protected in accordance with the HIPAA of 1996 
and any applicable local regulations. HIPAA regulations require that, in order to participate in the 
study, a patient must sign an authorization from the study that he or she has been informed of 
following: 
• What protected health information (PHI) will be collected from patients in this study 
• Who will have access to that information and why 
• Who will use or disclose that information 
• That health information may be further disclosed by the recipients of the information, 
and that if the information is disclosed the information may no longer be protected by 
federal or state privacy laws 
• The information collected about the research study will be kept separate from the 
patient’s medical records, but the patient will be able to obtain the research records 
after the conclusion of the study 
• Whether the authorization contains an expiration date 
• The rights of a research patient to revoke his or her authorization 
In the event that a patient revokes authorization to collect or use his or her PHI, the Investigator, 
by regulation, retains the ability to use all information collected prior to the revocation of patient 
authorization. For patients that have revoked authorization to collect or use PHI, attempts should 
be made to obtain permission to collect at least vital status (i.e., that the patient is alive) at the end 
of their scheduled study period. 
In compliance with ICH GCP guidelines and applicable parts of 21 CFR, it is a requirement that 
the Investigator and institution permit authorized representatives of Sponsor, the regulatory 
authorities, and the IRB/EC direct access to review the patient’s original medical records at the 
site for verification of study-related procedures and data.  
Measures to protect confidentiality include: only a unique study number and initials will identify 
patients in the eCRF system or other documents submitted to the Sponsor. Patient names or 
addresses will not be entered in the eCRF database system. No material bearing a patient’s name 
will be kept on file by Sponsor.  
13.4.2. 
Investigator and Staff Information 
Personal data of the Investigators and sub-Investigators may be included in the CRO database and 
shall be treated in compliance with all applicable laws and regulations. When archiving or 
processing personal data pertaining to the Investigator or sub-Investigator, the CRO shall take all 
appropriate measures to safeguard and prevent access to this data by any unauthorized party. 

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13.5. 
Financial Information 
The finances for this clinical study will be subject to a separate written agreement between the 
Sponsor and applicable parties. Any Investigator financial disclosures applicable to 21CFR Part 54 
shall be appropriately provided. 
14. 
RESEARCH RETENTION AND DOCUMENTATION OF THE 
STUDY 
14.1. 
Amendments to the Protocol 
Amendments to the protocol shall be planned, documented, and signature authorized prior to 
implementation. 
The protocol will only be amended by the Sponsor and requires approval of the IRB/EC. Changes 
to the protocol must be in the form of a written amendment; changes other than those of a simple 
administrative nature (e.g., a new telephone number for a medical monitor) must be submitted by 
the investigator to the local IRB/EC and such amendments will only be implemented after approval 
of the requisite IRB/EC. All amendments will also be submitted to the FDA and/or local regulatory 
authorities by the Sponsor. Protocol changes to eliminate an immediate hazard to a study patient 
may be implemented by the investigator immediately. The investigator must then immediately 
inform their IRB/EC and the Sponsor will immediately notify applicable regulatory authorities. 
14.2. 
Documentation Required to Initiate the Study 
Before the study may begin certain documentation required by FDA regulations and ICH GCP 
must be provided by the Investigator. The required documentation should be submitted to the 
CRO. Documents at a minimum required to begin a study in the US include, but are not limited 
to, the following: 
• A signed Investigator Protocol Agreement and contract 
• A copy of the official IRB/EC approval of the study, and the IRB/EC members list, or 
the multiple project assurance number from the US Federal Wide Assurance program 
where applicable 
• Current (i.e., updated no more than 24 months prior) Curricula Vita for the Investigator 
and any sub-Investigator(s) who will be involved in the study 
• A copy of the current medical license for the Investigator and each sub-Investigator 
• Indication of appropriate accreditation for any laboratories to be used in the study and 
a copy of the normal ranges for tests to be performed by that laboratory 
• Original Form FDA 1572 (Statement of Investigator) or equivalent form, appropriately 
completed and signed 
• A copy of the IRB/EC-approved ICF (and PIS, if applicable) containing permission for 
audit by representatives of CRO, the Sponsor, the IRB, and the FDA and other 
regulatory agencies (as applicable) 

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• Financial disclosure forms for all Investigators listed on Form FDA 1572 
• Site qualification reports, where applicable 
• Verification of Investigator acceptability from local and/or national debarment list(s)  
• Any other material provided to potential study participants with information about the 
study (e.g., advertisements) 
14.3. 
Study Documentation and Storage 
The Investigator must maintain a list of appropriately qualified persons to whom he/she has 
delegated study duties and should ensure that all persons assisting in the conduct of the study are 
informed of their obligations. All persons authorized to make entries and/or corrections on the 
eCRFs are to be included. All entries in the patient’s eCRF are to be supported by source 
documentation where appropriate. 
Source documents are the original documents, data, records, and certified copies of original 
records of clinical findings, observations, and activities from which the patient’s eCRF data are 
obtained. These can include, but are not limited to, hospital records, clinical and office charts, 
laboratory, medico-technical department and pharmacy records, diaries, microfiches, ECG traces, 
copies or transcriptions certified after verification as being accurate and complete, photographic 
negatives, microfilm or magnetic media, X-rays, and correspondence. 
The Investigator and each study staff member are responsible for maintaining a comprehensive 
and centralized filing system (e.g., regulatory binder or investigator study file (ISF) of all 
study-related (essential) documentation, suitable for inspection at any time by representatives from 
the Sponsor and/or applicable regulatory authorities. The ISF must consist of those documents that 
individually or collectively permit evaluation of the conduct of the study and the quality of the 
data produced. The ISF should contain as a minimum all relevant documents and correspondence 
as outlined in ICH GCP Section 8 and 21 CFR Part 312.57, including key documents such as the 
IB and any amendments, protocol and any amendments, signed ICFs, copies of completed eCRFs, 
IRB approval documents, Financial Disclosure forms, patient identification lists, enrollment logs, 
delegation of authority log, staff qualification documents, laboratory normal ranges, records 
relating to the study drug including accountability records. Drug accountability records should, at 
a minimum, contain information regarding receipt, shipment, and disposition. Each form of drug 
accountability record, at a minimum, should contain Investigator name, date drug 
shipped/received, date, quantity and batch/code, or lot number for identity of each shipment. In 
addition, all original source documents supporting entries in the eCRF must be maintained and be 
readily available. 
The Sponsor shall maintain adequate investigational product records and financial interest records 
as per 21CFR Part 54.6 and Part 312.57 for no less than 2 years after the last marketing application 
has been approved by FDA; or, in the event that the marketing application has not been approved 
by FDA, for no less than 2 years after the last shipment/delivery of the drug for investigational use 
is discontinued and FDA has been notified of the discontinuation. 
The IRB shall maintain adequate documentation/records of IRB activities as per 21 CFR 
Part 56.115 for at least 3 years after completion of the research. 

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The Investigator shall maintain adequate records of drug disposition, case histories, and any other 
study-related records as per 21 CFR Part 312.62 for no less than 2 years after the last marketing 
application has been approved by FDA; or, in the event that the marketing application has not been 
approved by FDA, for no less than 2 years after the last shipment/delivery of the drug for 
investigational use is discontinued and FDA has been notified of the discontinuation. 
To enable evaluations and/or audits from regulatory authorities or from the Sponsor or its 
representative, the Investigator additionally agrees to keep records, including the identity of all 
participating patients (sufficient information to link records [e.g., eCRFs, medical records]), all 
original, signed ICFs, and copies of all eCRFs, SAE Reporting forms, source documents, detailed 
records of treatment disposition, and related essential regulatory documents. The documents listed 
above must be retained by the Investigator for as long as needed to comply with national and 
international regulations (generally 2 years after discontinuing clinical development or after the 
last marketing approval). The Sponsor or its representatives will notify the Investigator(s)/ 
institutions(s) when the study-related records are no longer required. 
If the Investigator relocates, retires, or for any reason withdraws from the study, both the Sponsor 
and its representative should be prospectively notified. The study records must be transferred to 
an acceptable designee, such as another Investigator, another institution, or to the Sponsor. The 
Investigator must obtain the Sponsor’s written permission before disposing of any records, even if 
retention requirements have been met. All study files will be maintained by the Sponsor or its 
representative throughout the study and will be transferred to the Sponsor at the conclusion of the 
study. 
14.4. 
Data Collection 
The study eCRF is the primary data collection instrument for the study. Electronic case report 
forms (eCRF) will be completed using the English language and should be kept current to enable 
the Sponsor to review the patients’ status throughout the course of the study. 
In order to maintain confidentiality, only study number, patient number, and year of birth will 
identify the patient in the eCRF system. If the patient’s name appears on any other document (e.g., 
laboratory report), it must be obliterated on the copy of the document to be supplied to the CRO 
and replaced instead with the patient number and patient’s initials. The Investigator will maintain 
a personal patient identification list (patient numbers with corresponding patient identifiers) to 
enable records to be identified and verified as authentic. Patient data/information will be kept 
confidential, and will be managed according to applicable local, state, and federal regulations. 
All data requested by the eCRF system must be supported by and be consistent with the patient’s 
source documentation. All missing data must be explained. When a required laboratory test, 
assessment, or evaluation has not been done or an “Unknown” box is not an option on the eCRF, 
a note should be created verifying that the field was “Not Done” or “Unknown”. For any entry 
errors made, the error(s) must be corrected, and a note explaining the reason for change should be 
provided. 
The Investigator will electronically sign and date the patient eCRF indicating that the data in the 
eCRF has been assessed. Each completed eCRF will be signed and dated by the Investigator, once 
all data for that patient is final. 

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15. 
PUBLICATION POLICY 
Elevation Oncology, as the Sponsor, has proprietary interest in this study. Authorship and 
manuscript composition will reflect joint cooperation between the Investigator and Elevation 
Oncology personnel. Authorship will be established prior to the writing of the manuscript in 
alignment with International Committee of Medical Journal Editors (ICMJE) authorship 
recommendations. No manuscripts or presentations regarding this study will be submitted for 
publication without written authorization from Elevation Oncology. 

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Naidoo J, Murphy C, Atkins MB, et al. Society for Immunotherapy of Cancer (SITC) consensus definitions 
for immune checkpoint inhibitor-associated immune-related adverse events (irAEs) terminology. 
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Nakayama I, Shinozaki E, Sakata S, et al. Enrichment of CLDN18-ARHGAP fusion gene in gastric cancers 
in young adults. Cancer Sci. 2019;110(4):1352-1363. doi:10.1111/cas.13967 
National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology (NCCN 
Guidelines), in Version 2.2021. 
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OPDIVO (nivolumab) [package insert]. Princeton, NJ: Bristol-Myers Squibb Company, 2018. 
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 
4:252-64. doi: 10.1038/nrc3239. PMID: 22437870 
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Petric, Z, Žuntar, I, Putnik, P, & Bursać Kovačević, D. Food-Drug Interactions with Fruit Juices. Foods. 
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Urothelial Cancer. N Engl J Med. 2024;390(10):875-888. doi:10.1056/NEJMoa2312117 
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Ramos-Casals M, Brahmer JR, Callahan MK, et al. Immune-related adverse events of checkpoint inhibitors. 
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Factors. World J Oncol. 2019;10(1):10-27. doi:10.14740/wjon1166 
Rha SY, Oh DY, Yañez P, et al. Pembrolizumab plus chemotherapy versus placebo plus chemotherapy for 
HER2-negative advanced gastric cancer (KEYNOTE-859): a multicentre, randomised, double-blind, 
phase 3 trial. Lancet Oncol. 2023;24(11):1181-1195. doi:10.1016/S1470-2045(23)00515-6 
Sahin U, Koslowski M, Dhaene K, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for 
therapeutic antibody development. Clin Cancer Res. 2008;14(23):7624-7634. doi:10.1158/1078-
0432.CCR-08-1547 
Sahin U, Schuler M, Richly H, et al. A phase I dose-escalation study of IMAB362 (Zolbetuximab) in 
patients with advanced gastric and gastro-oesophageal junction cancer. Eur J Cancer. 2018;100:17-26. 
doi:10.1016/j.ejca.2018.05.007 
Sahin U, Türeci Ö, Manikhas G, et al. FAST: a randomised phase II study of zolbetuximab (IMAB362) 
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Shitara. K, Lordick, F.et al. Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-
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volume 401, issue 10389, p1655-1668, May 20, 2023. doi.org/10.1016/S0140-6736(23)00620-7 
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Shah MA, Shitara K, Ajani JA, et al. Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or 
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2023;29(8):2133-2141. doi:10.1038/s41591-023-02465-7 
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Wilke. H, Muro. K et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with 
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Yao F, Kausalya JP, Sia YY, et al. Recurrent Fusion Genes in Gastric Cancer: CLDN18-ARHGAP26 
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Zhang J, Dong R, Shen L. Evaluation and reflection on claudin 18.2 targeting therapy in advanced gastric 
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Zhou H, Yuan Y, Nie L. Accuracy, Safety, and Reliability of Novel Phase I Trial Designs. Clin Cancer 
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17. 
APPENDICES 
Appendix A. Guidelines for Women of Childbearing Potential and Fertile Male Patients 
EO-3021 is an anti-CLDN18.2 antibody conjugated to a cytotoxic payload (MMAE). Based on 
its mechanism of action, dostarlimab can cause fetal harm when administered to a pregnant 
woman. The teratogenicity of ramucirumab is not known.  
Female Patients: 
Women of childbearing potential, defined as all women physiologically capable of becoming 
pregnant, must use highly effective contraception during the study and for 6 months (or longer as 
required by local regulations including 6 months plus 5 half-lives for female patients in South 
Korea) after stopping treatment with EO-3021. 
All women of childbearing potential must use highly effective methods of contraception for a 
period of 6 months after the last EO-3021 infusion. Highly effective contraception methods include 
the following: 
1. Total abstinence (when this is in line with the preferred and usual lifestyle of the patient). 
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) and 
withdrawal are NOT acceptable methods of contraception. 
2. Female sterilization (has had surgical bilateral oophorectomy with or without 
hysterectomy), total hysterectomy, or tubal ligation at least 6 weeks before taking study 
treatment. In case of oophorectomy alone, only when the reproductive status of the woman 
has been confirmed by follow up hormone level assessment. 
3. Male partner sterilization (at least 6 months prior to screening). For female patients on the 
study the vasectomized male partner should be the sole partner for that patient. 
4. Use of oral, injected, or implanted hormonal methods of contraception or other forms of 
hormonal contraception that have comparable efficacy (failure rate <1%), for example 
hormone vaginal ring or transdermal hormone contraception 
5. Use of IUDs are not acceptable due to increased risks of infection and bleeding in this 
population. However, IUD inserted prior to consent may remain in place, and a second 
method of contraception is mandated. 
6. In case of use of oral contraception, women must be stable on the same pill for a minimum 
of 3 months before taking study treatment. 
Women who are not of reproductive potential (defined as postmenopausal for at least 
12 consecutive months [i.e., have had no menses without an alternative medical cause] or have 
undergone hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy) are eligible 
without requiring the use of contraception.  
Unacceptable Contraception Methods for women of childbearing potential include: 
• IUD progesterone T 
• Female condom 
• Natural family planning (rhythm method) or breastfeeding 

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• Fertility awareness 
• Withdrawal 
• Cervical shield 
Male Patients: 
Fertile male patients, defined as all males physiologically capable of conceiving offspring, with 
female partners of childbearing potential must use condoms plus spermicidal agent during the 
study treatment period and for 3 months after the last dose of study drug (or longer as required by 
local regulations including 3 months plus 5 half-lives for male patients in South Korea), and should 
not father a child during this period. 
Male patients must also refrain from donating sperm during for the same time period. 
Reporting of Unintended Pregnancies 
To ensure patient safety, each pregnancy in a patient on study treatment must be reported to the 
CRO Safety Department within 24 hours of learning of its occurrence. The pregnancy should be 
followed up for 3 months after the completion of the pregnancy to determine outcome, including 
spontaneous or voluntary termination, details of the birth, and the presence or absence of any birth 
defects, congenital abnormalities, or maternal and/or newborn complications. 
Pregnancy should be recorded on a Clinical Study Pregnancy Form and reported by the 
Investigator to the CRO Safety Department. Pregnancy follow-up should be recorded in the same 
form and should include an assessment of the possible relationship to the study drug of any 
pregnancy outcome. Any SAE experienced during pregnancy must be reported on the SAE Report 
Form. 
Pregnancy outcomes must be collected for the female partners of any males who took study 
treatment in this study. Consent to report information regarding these pregnancy outcomes should 
be obtained from the mother. 
 
 

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Appendix B. Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 
Definitions 
Response and progression will be evaluated in this trial using the Response Evaluation Criteria in 
Solid Tumors (RECIST) version 1.1. Lesions are either measurable or non-measurable using the 
criteria provided below. The term “evaluable” in reference to measurability will not be used, as it 
does not provide additional meaning or accuracy. 
Baseline Eligibility 
Measurable Disease: 
Tumor lesions:  Must be accurately measured in at least one dimension 
(longest diameter in the plane of measurement is to be recorded) with a 
minimum size of: 
• 
10 mm by CT by computerized tomography (CT scan slice thickness 
no greater than 5 mm). 
• 
10 mm caliper measurement by clinical exam (lesions that cannot be 
accurately measured with calipers should be recorded as non-
measurable). 
• 
20 mm by chest x-ray. 
Skin lesions:  Documentation by color photography, including a ruler to 
estimate the size of the lesion, is recommended. 
Malignant lymph nodes:  To be considered pathologically enlarged and 
measurable, a lymph node must be ≥15 mm in short axis when assessed by 
CT scan. At baseline and in follow-up, only the short axis will be measured 
and followed.  
Non-Measurable Disease: 
All other lesions, including small lesions (longest diameter <10 mm or 
pathological lymph nodes with ≥10- to <15-mm short axis) as well as truly 
non-measurable lesions. Lesions considered truly non-measurable include: 
leptomeningeal disease, ascites, pleural or pericardial effusion, inflammatory 
breast disease, lymphangitic involvement of skin or lung, abdominal masses, 
abdominal organomegaly identified by physical exam that is not measurable 
by reproducible imaging techniques.  
Target Lesions: 
The most reproducible measurable lesions, up to a maximum of 2 lesions 
per organ and 5 lesions in total, representative of all involved organs should 
be identified as target lesions and recorded and measured at baseline.   
Target lesions should be selected on the basis of their size (lesions with the 
longest diameter), should be representative of all involved organs, and in 
addition should be those that lend themselves to reproducible repeated 
measurements. Pathological nodes which are defined as measurable and that 
may be identified as target lesions must meet the criterion or a short axis of 
≥15 mm by CT scan. 
A sum of the diameters (longest for non-nodal lesions, short axis for nodal 
lesions) for all target lesions will be calculated and reported as the baseline 
sum diameters. If lymph nodes are to be included in the sum, then as noted 
above, only the short axis is added into the sum. The baseline sum diameters 
will be used as reference to further characterize any objective tumor 
response. 
Non-Target Lesions: 
All other lesions should be identified as non-target lesions at baseline.  
Measurements of these lesions are not required, but the presence or 
absence of each should be noted throughout follow-up. 
 

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Guidelines for Evaluation of Measurable Disease 
All measurements should be taken and recorded in metric notation, using a ruler or calipers. All 
baseline evaluations should be performed as closely as possible to the beginning of treatment, as 
per protocol screening requirements. 
The same method of assessment and the same technique should be used to characterize each 
identified and reported lesion at baseline and during follow-up. Imaging-based evaluation is 
preferred to evaluation by clinical examination when both methods have been used to assess the 
anti-tumor effect of a treatment. 
 
Clinical Lesions: 
Clinical lesions will only be considered measurable when they are 
superficial (e.g., skin nodules and palpable lymph nodes) and ≥10 mm in 
diameter. In the case of skin lesions, documentation by color photography, 
including a ruler to estimate the size of the lesion, is recommended. 
Chest X-ray: 
Lesions on chest X-ray are acceptable as measurable lesions when they are 
clearly defined and surrounded by aerated lung. However, a CT scan is 
preferable. 
Conventional CT and MRI: 
CT, MRI:  CT is the best currently available and reproducible method to 
measure lesions selected for response assessment. This guideline has defined 
measurability of lesions on CT scan based on the assumption that CT slice 
thickness is 5 mm or less. When CT scans have slice thickness greater than 
5 mm, the minimum size for a measurable lesion should be twice the slice 
thickness. MRI is also acceptable in certain situations (e.g., for body scans).  
Ultrasound: 
When the primary trial endpoint is objective response, ultrasound should not 
be used to measure tumor lesions. It is, however, a possible alternative to 
clinical measurements of superficial palpable lymph nodes, subcutaneous 
lesions, and thyroid nodules. Ultrasound may also be useful to confirm the 
complete disappearance of superficial lesions usually assessed by clinical 
examination. 
Endoscopy and Laparoscopy: 
Use of endoscopy and laparoscopy for objective tumor evaluation has not 
yet been fully and widely validated. Therefore, use of these techniques for 
objective tumor response should be restricted to validation purposes in 
specialized centers. Such techniques can be useful in confirming complete 
pathological response when biopsies are obtained. 
Tumor Markers: 
Tumor markers alone cannot be used to assess response. If markers are 
initially above the upper limit of normal, they must normalize for a subject 
to be considered in complete clinical response when all lesions have 
disappeared. 
Cytology and Histology: 
Cytology and histology can be used to differentiate between partial response 
(PR) and complete response (CR) in rare cases (e.g., after treatment to 
differentiate between residual benign lesions and residual malignant lesions 
in tumor types such as germ cell tumors). 

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Response Criteria 
Evaluation of Target Lesions 
Complete Response (CR):  
Disappearance of all target lesions. 
Partial Response (PR): 
 
At least a 30% decrease in the sum of diameters of target lesions, taking as 
reference the baseline sum diameters. 
Stable Disease (SD): 
 
Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD, taking as reference the smallest (nadir) sum of diameters 
since the treatment started. 
Progressive Disease (PD): 
 
At least a 20% increase in the sum of the diameters of target lesions, taking 
as reference the smallest (nadir) sum since the treatment started, or the 
appearance of one or more new lesions. Requires not only 20% increase, but 
absolute increase of a minimum of 5 mm over sum. 
Evaluation of Non-Target Lesions 
Complete Response (CR): 
Disappearance of all non-target lesions and normalization of tumor markers.  
All lymph nodes must be non-pathological in size (<10 mm short axis). 
Stable Disease (SD): 
 
Persistence of one or more non-target lesions and/or persistence of tumor 
marker level above the normal limits. 
Progressive Disease (PD): 
 
Appearance of one or more new lesions and/or unequivocal progression of 
existing non-target lesions. When the subject also has measurable disease, 
to achieve “unequivocal progression” on the basis of the non-target disease, 
there must be an overall level of substantial worsening in non-target disease 
such that, even in presence of SD or PR in the target disease, the overall 
tumor burden has increased sufficiently to merit discontinuation of therapy. 
Evaluation of Best Overall Response 
As detailed above, the best overall response is the best response recorded from the start of the 
treatment until disease progression/recurrence (taking as reference for PD the smallest 
measurements recorded since the treatment started). In general, the subject’s best response 
assignment will depend on the achievement of both measurement and confirmation criteria.   
Confirmation of response (by repeat scans after 4 weeks) is required for trials in which response 
rate is the primary endpoint but is not required in randomized trials or trials with primary survival 
endpoints (i.e., where response is not a primary endpoint). 
Target Lesions 
Non-Target Lesions 
New Lesions 
Overall Response 
CR 
CR 
NO 
CR 
CR 
SD 
NO 
PR 
CR 
NE 
NO 
PR 
PR 
SD OR NE 
NO 
PR 
SD 
SD OR NE 
NO 
SD 
PD 
ANY 
YES OR NO 
PD 
ANY 
PD 
YES OR NO 
PD 
ANY 
ANY 
YES 
PD 

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In some circumstances, it may be difficult to distinguish residual disease from normal tissue.  
When the evaluation of a CR depends upon this determination, it is recommended that the residual 
lesion be investigated by fine needle aspirate or biopsy to confirm the CR status. 
When nodal disease is included in the sum of target lesions, and the nodes decrease to “normal” 
size (<10 mm), they may still have a measurement reported on scans. This measurement should be 
recorded even though the nodes are normal in order not to overstate progression, should it be based 
on increase in size of the nodes. As noted earlier, this means that subjects with CR may not have 
a total sum of “zero” on the eCRF. 
 
 

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Appendix C. Schedule of Assessments 
Study Procedures 
 
PRETREATMENT 
TREATMENT (21-day cycles) 
POST 
TREATMENT 
Screeninga 
Cycle 1 (21-day Cycle) 
Cycle 2 
and 
beyond 
(21-day 
Cycle) 
EOTc 
(within 
28 ±3 
days of 
last 
dose) 
Long-term 
Follow-upd 
(every 
3 months 
±28 days) 
 
D1b 
D2 
D3 
D5 
(± 1 day) 
D8 
(± 1 day) 
D15 
(± 1 day) 
D1  
(±3 days) 
 
 
CLINICAL ASSESSEMENTS 
Informed Consente  
X 
 
 
 
 
 
 
 
 
 
Archival Tumor Tissue Collectionf 
X 
 
 
 
 
 
 
 
 
 
Fresh Tumor Tissue Biopsyf 
X 
 
 
 
 
 
 
 
Xf 
 
Patient Inclusion/Exclusion Criteria  
X 
X 
 
 
 
 
 
 
 
 
Medical/Surgical/Cancer History and 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Physical Examinationg  
X 
X 
 
 
 
X 
X 
X 
X 
 
Vital Signsh 
X 
Xh 
 
 
 
X 
X 
Xh 
X 
 
ECOG PS  
X 
X 
 
 
 
 
 
X 
X 
 
Adverse Event Assessmenti 
X 
 
Concomitant Medication Reviewj  
X 
 
Ophthalmic Examinationk  
X 
 
 
 
 
 
 
X 
X 
 
CLINICAL LABORATORY ASSESSMENTS 
Triplicate ECGl  
X 
Xb 
X 
 
X 
X 
X 
X 
X 
 
Chemistry (CMP)m  
X 
Xb 
 
 
 
X 
X 
X 
X 
 
CBC with Differentialn   
X 
Xb 
 
 
 
X 
X 
X 
X 
 
Thyroid Stimulating Hormone (TSH) (Arms A3 
and B3 [combination with dostarlimab] only) 
X 
Xb 
 
 
 
 
 
X 
X 
 
Tumor Markero 
X 
Xb 
 
 
 
 
 
X 
X 
 
Coagulation profile: PT/INR/aPTTp 
X 
Xb 
 
 
 
 
 
X 
X 
 
Urinalysisq  
X 
Xb 
 
 
 
 
 
X 
X 
 
Serum or urine Pregnancy Testr  
X 
Xb 
 
 
 
 
 
X 
X 
 
PK Assessments 
 
X 
X 
 
X 
X 
X 
X 
X 
 
ADA/nAb Assessmentt 
 
X 
 
 
 
 
 
X 
X 
 
STUDY DRUG ADMINSTRATION 
EO-3021 infusionu  
 
X 
 
 
 
 
 
X 
 
 

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Study Procedures 
 
PRETREATMENT 
TREATMENT (21-day cycles) 
POST 
TREATMENT 
Screeninga 
Cycle 1 (21-day Cycle) 
Cycle 2 
and 
beyond 
(21-day 
Cycle) 
EOTc 
(within 
28 ±3 
days of 
last 
dose) 
Long-term 
Follow-upd 
(every 
3 months 
±28 days) 
 
D1b 
D2 
D3 
D5 
(± 1 day) 
D8 
(± 1 day) 
D15 
(± 1 day) 
D1  
(±3 days) 
 
 
Ramucirumab infusionv 
 
X 
 
 
 
 
 
X 
 
 
Dostarlimab infusionw 
 
X 
 
 
 
 
 
X 
 
 
DLT Assessmentx  
 
X 
 
 
 
TUMOR ASSESSMENT (±7 days) 
CT/MRI scany 
X 
 
 
 
 
 
 
Xy 
X 
Xz 
SURVIVAL FOLLOW UP 
Overall Survival Reportingd 
 
 
 
 
 
 
 
 
 
X 
ADA = anti-drug antibody; AE = adverse event; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate aminotransferase; BP = blood 
pressure; BUN = blood urea nitrogen; C1D1 = Cycle 1 Day 1; C1D8 = Cycle 1 Day 8; C1D15 = Cycle 1 Day 15; CBC = complete blood count; CMP = comprehensive metabolic 
profile; CT = computed tomography; DLT = dose limiting toxicity; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EOI = end of infusion; EOT = end 
of treatment; HEENT = head, eyes, ears, nose, and throat; HR = heart rate; INR = international normalized ratio; LFT = liver function test; MRI = magnetic resonance imaging; 
nAb = neutralizing antibodies; OCT = optical coherence tomography; PK = pharmacokinetic; PS = performance status; PT = prothrombin time; PTT = partial thromboplastin 
time; RR = respiratory rate; SAE = serious adverse event; SpO2 = oxygen saturation; TSH = thyroid-stimulating hormone; WBC = white blood cells 
a Unless otherwise specified, all screening procedures must be performed within 28 days of C1D1. 
b If screening laboratory tests are completed within 3 days prior to C1D1, pre-dose laboratory tests on C1D1 do not need to be repeated. Laboratory tests (not inclusive of 
PK/ADA/nAb) for D1 of each cycle may be completed within 3 days prior to the dosing visit. 
c EOT visit: In clinic visit to occur 28 (±3) days after last dose of study drug. If treatment is discontinued because of toxicity or for any other reason(s) at a scheduled treatment 
visit and no study treatment is administered, that visit may fulfill the EOT visit. If a patient discontinues EO-3021 due to RECIST progression, imaging studies at EOT visit are 
not required.   
d Long term follow-up to be every 3 months (±28 days) from the date of last treatment until death, loss to follow-up, withdrawal of consent, or study termination by the Sponsor. 
May be conducted in person or via telephone/email/electronic medical record. Survival follow-up should include collection of any new anti-cancer therapies and procedures 
taken after EOT visit. Attempts should be made to obtain any death information available via public records. 
e Must be signed prior to any protocol-specific procedures.    
f Patients enrolled to Part A (all arms): A fresh tumor biopsy should be performed during the screening period if determined to be medically feasible by the Investigator. In addition 
to obtaining a fresh tumor tissue biopsy, an archival tumor tissue sample (collected within the past 24 months) should be provided to the central laboratory for retrospective 
testing. Patients enrolled to Part B (all arms): Prospective central testing for CLDN18.2 is required for patients enrolled in Part B (all arms). After signing informed consent, a 
FFPE block or a minimum of 6 unstained slides of tumor tissue from a biopsy obtained within 6 months of enrollment should be provided to central laboratory for prospective 
testing. If the patient received prior CLDN18.2 direct therapy after the date of the archival sample, a fresh tissue biopsy must be performed. For all patients (Part A and Part B) 
a fresh tissue biopsy at EOT is recommended to explore mechanisms of resistance. 

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g Comprehensive physical examination should be performed at the screening visit and on C1D1. Body systems should include: general, HEENT, respiratory, cardiovascular, 
abdomen, extremities, neurologic, and psychiatric. Limited/problem/symptom focused physical examinations to include at a minimum HEENT, cardiovascular, respiratory, and 
abdomen should be performed at C1D8, C1D15 and Day 1 of each cycle starting at Cycle 2. Physical exam for C1D1 may be completed within 3 days prior to the visit. 
h Vital signs include the following: height (at screening only), weight (dosing is based on patient’s body weight on Day 1 of each cycle (or at each dosing day if change in body 
weight is > 10% or if required by institutional policy), BP in seated position, HR, RR, oral temperature, and SpO2. For C1D1, BP in a seated position, HR, RR, temperature, and 
SpO2 will be collected pre-dose (within 10 minutes prior), every 30 mins during infusion, end of infusion EOI within 10 minutes after), and 1-hour post-EOI (±10 minutes).  For 
all subsequent cycles, vital signs will be collected pre-dose (within 10 minutes prior) and EOI within 10 minutes after).  
i Monitor and record AEs and SAEs throughout the study and 28 days after the last dose of study treatment or initiation of alternative anticancer treatment, whichever occurs first. 
After this period, investigators are only required to report SAEs that they become aware of and are thought to be related to EO-3021. Record all AEs, regardless of relationship 
to study treatment, that occur after initiation of first study treatment until EOT. After informed consent, but prior to initiation of study treatment, only SAEs caused by a 
protocol-mandated intervention will be collected (e.g., SAEs related to invasive procedures such as biopsies). All SAEs should be reported to the Sponsor or designee within 
24 hours of investigator awareness. 
j Record all concomitant medications including any prescription medications, over-the-counter preparations, herbal/vitamin supplements, and transfusions received by patients 
from 7 days preceding C1D1 through the EOT or start of a new anticancer treatment. 
k Ophthalmic examination will be performed at screening, during treatment (performed at end of Cycle 2 and every other cycle thereafter) and at EOT and will include OCT, slit 
lamp examination, and visual acuity exam. Additional exams should be guided by specific ocular signs and symptoms as clinically indicated. Ophthalmic exams conducted 
within a ± 7-day window are acceptable. 
l After the patient has been supine for at least 5 minutes, triplicate 12-lead ECGs will be collected as closely together as possible but within 30 minutes pre-dose and 30 minutes 
(±10 minutes) post dose on C1D1. ECG on Days 2, 5, 8, and 15 to coincide with PK sampling (±1 hour). ECG to be pre-dose on Day 1 of each cycle through Cycle 5, then pre-
dose Day 1 of every other cycle starting with Cycle 7. 
m CMP to include sodium, potassium, chloride, BUN, creatinine, glucose (non-fasting), albumin, total protein, calcium, magnesium, phosphorus, uric acid, and LFTs (ALT, AST, 
total and direct bilirubin, alkaline phosphatase) 
n CBC with differential including hemoglobin, hematocrit, platelets, WBCs including absolute counts for neutrophils, lymphocytes, and monocytes.  
o Only in patients with tumors where monitoring of tumor markers is clinically relevant (e.g., CA19-9, CEA, etc.).   
p Coagulation profile to include PT/INR and aPTT (or PTT) on Day 1 of every other cycle starting with Cycle 3; additional testing may be performed as clinically indicated. 
q Dipstick urinalysis with reflex to urinalysis with microscopic examination as clinically indicated. At Screening and prior to each dose, for Arms A2 and B2 (Combination of 
EO-3021 plus ramucirumab), the patient’s urinary protein must be ≤1+ on dipstick or routine urinalysis; if urine dipstick or routine analysis is ≥2+, a 24-hour urine collection 
for protein must be performed and must demonstrate <1000 mg of protein in 24 hours to allow participation in Arms A2 and B2.  
r A pregnancy test should only be performed for women of childbearing potential.  If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test is 
required.  
s PK blood sample collection on C1 pre-dose (within 30 minutes prior), and at end of infusion (within 10 minutes) and post-infusion at 1 hour (±10 min), 2 hours (±10 min), and 
4 hours (±10 min). D2 at 24 hours post infusion (±2 hr.), D5 at 96 hours post infusion (± 1 day), D8 at 168 hours (±1 day) post infusion and D15 at 336 hours (±1 day) post 
infusion. Cycles 2-4: D1 pre-dose (within1 hr. prior) and within 10 mins after end of infusion. Cycle 5 and beyond, PK samples will be collected every other cycle (Cycle 5, 7, 
9, 11, etc.) on D1 pre-dose (within 1 hr. prior) and within 10 min after end of infusion. 
t ADA/nAb blood samples will be collected pre-dose (within 30 min prior) on Day 1 of every other cycle (Cycle 1, 3, 5, etc.) and at EOT. Ad hoc ADA samples can be collected 
at the Investigator or Sponsor’s discretion.   
u Study drug administration intravenously once every 3 weeks (3QW) ± 3 days.  Laboratory assessments should be reviewed prior to treatment. 
v Ramucirumab will be administered to patients enrolled to Arms A2 and B2 at 10 mg/kg IV Q3W ± 3 days. Ramucirumab will be administered after EO-3021. Laboratory 
assessments should be reviewed prior to treatment. 
w Dostarlimab will be administered to patients enrolled in Arms A3 and B3 at 500 mg IV Q3W ± 3 days. Dostarlimab will be administered after EO-3021. Laboratory assessments 
should be reviewed prior to treatment. 
x DLT assessment to be performed throughout Cycle 1 with a minimum observation period of 21 days from first dose of study drug.  

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y Imaging (CT with contrast or MRI) of the chest, abdomen, pelvis is required at a minimum throughout the study with scans of additional regions (such as of the neck or extremities 
etc.) to be included as appropriate based on presence of disease or symptoms. The same imaging modality should be used throughout the study. Imaging studies must be 
performed every 6 weeks (±7 days) from C1D1 for the first 12 months. After 12 months, imaging studies may be conducted every 12 weeks (±7 days). Scans should be performed 
following the outlined schedule even if doses are delayed/interrupted/missed. Confirmation of response (by repeat scans after 4 weeks) is required. 
z If a patient discontinues study treatment for reasons other than disease progression (e.g., due to toxicities) tumor assessments with imaging will continue until initiation of next 
anti-cancer therapy, death, or withdrawal of consent, whichever occurs first. 
 
 

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Appendix D. Immune Checkpoint Inhibitor Dose Modification and Toxicity Management Guidelines for Suspected Drug related 
Immune-mediated AEs (imAEs) 
Adverse Reaction 
Toxicity grade or 
conditions 
(NCI-CTCAE 
v5) 
Action Taken with Study 
Intervention 
imAE management with 
corticosteroids and/or other 
therapies 
Monitoring and follow-up 
General instructions:  This table provides guidelines for dose modifications / dose discontinuations for adverse events that are suspected to be imAEs related to 
the ICI. 
Corticosteroid taper should be initiated upon AE improving to Grade ≤1 and continue to taper over at least 4 weeks. 
For situations where study intervention has been withheld, administration can be resumed after the imAE has been reduced to Grade ≤1 and corticosteroid has been 
tapered. Study intervention should be permanently discontinued if the imAE does not resolve within 12 weeks of last dose or corticosteroids cannot be reduced to 
≤10 mg/day prednisone, or equivalent, within 12 weeks. 
For severe and life-threatening imAEs, IV corticosteroid should be initiated first, followed by oral steroid. Other immunosuppressive treatment should be initiated 
if imAEs cannot be controlled by corticosteroids. 
Adrenal insufficiency 
Grade 2, 3, or 4 
Hold until administration of 
HRT results in return to 
adequate hormone levels based 
on laboratory values and restart 
dosing when toxicity resolves 
to Grade ≤1. For recurrent or 
worsening Grade ≥2 adrenal 
insufficiency while adequate 
HRT is continuing, 
permanently discontinue study 
intervention. 
Start treatment with corticosteroids 
before other HRT to avoid adrenal 
crisis (hydrocortisone, slowly 
titrating doses down according to 
symptoms OR prednisone and 
fludrocortisone, titrating up or down 
based on BP, other symptoms, and 
laboratory assessments); 
participants with severe symptoms 
may require additional fluids (e.g., 
saline >2 L). 
• 
Monitor for cortisol level (AM), 
comprehensive metabolic panel (Na, 
K, CO2, glucose), and renin.  
• 
Ensure adequate endocrine evaluation 
(e.g., endocrine consultation). 
AST/ALT elevation, 
increased bilirubin, or 
hepatitis 
Grade 2 with AST 
or ALT >3 to 
5×ULN or total 
bilirubin >1.5 to 
3×ULN 
• 
Withhold. Restart when 
toxicity resolves to 
Grade ≤1. 
Inform Sponsor Medical 
Monitor before resuming dose 
Administer corticosteroids (initial 
dose of 0.5 to 1 mg/kg 
methylprednisolone or equivalent) 
followed by taper. 
• 
Inform Sponsor Medical Monitor 
• 
Monitor with LFTs (consider weekly 
or more frequently until liver enzyme 
value[s] return to baseline or are 
stable). 
• 
Ensure adequate hepatology 
evaluation (e.g., hepatologist 
consultation). 
• 
See Appendix E for liver chemistry 
monitoring guidance. 

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Adverse Reaction 
Toxicity grade or 
conditions 
(NCI-CTCAE 
v5) 
Action Taken with Study 
Intervention 
imAE management with 
corticosteroids and/or other 
therapies 
Monitoring and follow-up 
Grade 3 with AST 
or ALT >5×ULN 
up to 8×ULN 
• 
Discontinuea.  
See Appendix E for liver 
chemistry stopping criteria and 
monitoring guidance, and for 
liver rechallenge process and 
criteria. 
Administer corticosteroids (initial 
dose of 1 to 2 mg/kg 
methylprednisolone or equivalent) 
followed by taper. 
• 
Strongly recommend specialist 
hepatology evaluation 
• 
See Appendix E for liver chemistry 
monitoring guidance 
AST/ALT elevation, 
increased bilirubin, or 
hepatitis (cont) 
Grade 3 (AST or 
ALT >8×ULN up 
to 20×ULN) or 
total bilirubin > 
3×ULN (up to 
10×ULN)   
• 
Permanently discontinue. 
See Appendix E for liver 
chemistry stopping criteria and 
monitoring guidance. 
Administer corticosteroids (initial 
dose of 1 to 2 mg/kg 
methylprednisolone or equivalent) 
followed by taper 
• 
Inform Sponsor Medical Monitor 
• 
See Appendix E for liver chemistry 
monitoring guidance. 
• 
Strongly recommend specialist 
hepatology evaluation 
Grade 4 (AST or 
ALT > 20×ULN 
or total bilirubin > 
10×ULN)  
• 
Permanently discontinue. 
See Appendix E for liver 
chemistry stopping criteria and 
monitoring guidance.  
Administer corticosteroids (initial 
dose of 2 mg/kg 
methylprednisolone or equivalent), 
followed by taper. 
• 
Inform Sponsor Medical Monitor 
• 
See Appendix E for liver chemistry 
monitoring guidance. 
• 
Specialist hepatology evaluation is 
recommended. 
Diarrhea/colitis 
Grade 2 or 3 
• 
Restart when toxicity 
resolved to Grade ≤1. 
Administer corticosteroids (initial 
dose of 1 to 2 mg/kg 
methylprednisolone or equivalent) 
followed by taper. 
• 
Monitor participants for signs and 
symptoms of enterocolitis (e.g., 
diarrhea, abdominal pain, blood or 
mucus in stool with or without fever) 
and of bowel perforation (e.g., 
peritoneal signs and ileus). 
• 
Participants with Grade ≥2 diarrhea 
where colitis is suspected should 
consider GI consultation and an 
endoscopy to rule out colitis. 
• 
Participants with diarrhea/colitis 
should be advised to drink liberal 
quantities of clear fluids. If sufficient 
oral fluid intake is not feasible, fluid 
and electrolytes should be substituted 
via IV infusion. 

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Adverse Reaction 
Toxicity grade or 
conditions 
(NCI-CTCAE 
v5) 
Action Taken with Study 
Intervention 
imAE management with 
corticosteroids and/or other 
therapies 
Monitoring and follow-up 
Severe neurologic 
events (myasthenic 
syndrome/ myasthenia 
gravis, Guillain Barré 
syndrome, transverse 
myelitis) 
Grade 2, 3, or 4 
Permanently discontinue. 
• 
Consider high dose 
corticosteroids and other 
therapies as needed. 
It is highly recommended that 
investigators discuss any AEs with 
the sponsor before using infliximab. 
• 
Ensure adequate evaluation (e.g., 
neurology consultation). 
• 
Consider MRI of brain and/or spine 
depending on symptoms. 
• 
Consider inpatient management as 
clinically indicated. 
Hemophagocytic 
lymphohistiocytosis 
(HLH) 
Suspected HLH 
Withhold 
Obtain specialist opinion for 
diagnosis and management 
Obtain specialist opinion for monitoring 
and follow-up 
Confirmed 
Permanently discontinue. 
Obtain specialist opinion for 
management 
Obtain specialist opinion for monitoring 
and follow-up 
Hyperthyroidism 
Grade 3 or 4 
Hold until return to adequate 
hormone levels based on 
laboratory values and restart 
dosing when toxicity resolves 
to Grade ≤1. 
Treat with non-selective 
beta-blockers (e.g., propranolol) or 
thionamides as appropriate. 
• 
Monitor for signs and symptoms of 
thyroid disorders. 
• 
Ensure adequate evaluation (e.g., 
endocrine consultation). 
Hypophysitis 
Grade 3 or 4 
For Grade 3 or 4, hold until 
administration of HRT results 
in return to adequate hormone 
levels based on laboratory 
values and restart when 
toxicity resolves to Grade ≤1. 
For recurrence or worsening of 
Grade ≥2 hypophysitis after 
steroid taper has been 
completed and participant is on 
adequate HRT, permanently 
discontinue. 
Administer corticosteroids and 
initiate HRT as clinically indicated. 
• 
Monitor for signs and symptoms of 
hypophysitis (including 
hypopituitarism and adrenal 
insufficiency). 
• 
Ensure adequate evaluation (e.g., 
endocrine consultation). 

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Adverse Reaction 
Toxicity grade or 
conditions 
(NCI-CTCAE 
v5) 
Action Taken with Study 
Intervention 
imAE management with 
corticosteroids and/or other 
therapies 
Monitoring and follow-up 
Hypothyroidism 
Grade 3 or 4 
Hold until administration of 
HRT results in return to 
adequate hormone levels based 
on laboratory values and restart 
dosing when toxicity resolves 
to Grade ≤1. 
Initiate thyroid replacement 
hormones (e.g., levothyroxine or 
liothyronine) per SOC. 
• 
Monitor for signs and symptoms of 
thyroid disorders. 
• 
Monitor thyroid function tests. 
• 
Ensure adequate evaluation (e.g., 
endocrine consultation). 
• 
Exclude concomitant adrenal 
insufficiency (AM cortisol level). 
Encephalitis 
Any grade 
Permanently discontinue. 
• 
Consider IV acyclovir until 
PCR results obtained. 
• 
Trial with methylprednisolone; 
if severe, treatment with 
methylprednisolone. 
• 
If positive for autoimmune 
encephalopathy antibody or no 
improvement after 7 to 14 days, 
consider rituximab. 
• 
Ensure adequate evaluation to 
confirm etiology and/or exclude other 
causes. 
• 
Obtain specialist neurology 
consultation 
Myocarditis 
Any grade 
Permanently discontinue. 
• 
Administer high dose 
corticosteroids (1 g/day of IV 
methylprednisolone) for 3 to 5 
days, if responding and stable, 
switch to oral prednisone taper 
over 6 to 12 weeks based on 
clinical response and 
improvement in cardiac 
biomarkers. 
• 
If no improvement in 24-
48 hours, consider adding other 
potent immunosuppressive 
agents. 
• 
Ensure adequate evaluation (e.g., 
urgent cardiology consultation) to 
confirm etiology and/or exclude other 
causes. 

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Adverse Reaction 
Toxicity grade or 
conditions 
(NCI-CTCAE 
v5) 
Action Taken with Study 
Intervention 
imAE management with 
corticosteroids and/or other 
therapies 
Monitoring and follow-up 
Pneumonitis (adverse 
event of special 
interest for EO-3021) 
Grade 2 
Restart dosing when toxicity 
resolves to Grade ≤1. If 
Grade ≥2 recurs, permanently 
discontinue. 
Administer corticosteroids (initial 
dose of 1 to 2 mg/kg 
methylprednisolone or equivalent) 
followed by taper on improvement 
to Grade ≤1. 
• 
Monitor participants for signs and 
symptoms of pneumonitis. 
• 
Evaluate participants with suspected 
pneumonitis with radiographic 
imaging and initiate corticosteroid 
treatment. 
• 
Ensure adequate evaluation (e.g. 
specialist pulmonologist / respiratory 
opinion) 
• 
Add prophylactic antibiotics for 
opportunistic infections (e.g. PJP). 
Exfoliative 
dermatologic 
conditions (e.g. SJS, 
TEN, DRESS) 
Suspected 
DRESS, SJS, or 
TEN 
Withhold. 
• 
Treat with high potency topical 
steroids to affected areas. 
• 
Treat with prednisone. 
Ensure adequate evaluation (e.g., urgent 
dermatology consultation) to confirm 
etiology and/or exclude other causes. 
Confirmed 
DRESS, SJS, or 
TEN 
Permanently discontinue. 
Administer 1 to 2 mg/kg/day IV 
methylprednisolone; taper steroid 
when dermatitis is controlled. 
Recurrence of 
suspected drug related 
imAEs after 
resolution to ≤Grade 1 
Grade 1 or 2 
Withhold (except for 
pneumonitis, see above). 
Based on severity of AEs, 
administer appropriate treatment 
until symptoms improve to 
Grade ≤2. 
Ensure adequate evaluation (e.g., 
specialist opinion) 
Grade 3 or 4 
Permanently discontinue. 
Ensure adequate evaluation (e.g. specialist 
opinion) 
Renal failure or 
nephritis 
Grade 2 
 
Restart dosing when toxicity 
resolves to Grade ≤1. 
Start treatment with prednisone; if 
persistent Grade 2 beyond 1 week, 
prednisone/methylprednisolone. 
• 
Monitor participants for signs and 
symptoms, including monitoring of 
creatinine and urine protein every 3 to 
7 days. 
• 
Ensure adequate evaluation (e.g., 
nephrology consultation) to confirm 
etiology and/or exclude other causes. 

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Adverse Reaction 
Toxicity grade or 
conditions 
(NCI-CTCAE 
v5) 
Action Taken with Study 
Intervention 
imAE management with 
corticosteroids and/or other 
therapies 
Monitoring and follow-up 
> Grade 3 
 
Permanently discontinue. 
• 
Start treatment with 
prednisone/methylprednisolone. 
• 
Consider adding 1 of the 
following after 1 week of 
steroids: azathioprine, 
cyclosporine, 
cyclophosphamide, infliximab, 
mycophenolate. 
• 
Ensure adequate evaluation (e.g., 
nephrology consultation, renal 
biopsy) to confirm etiology and/or 
exclude other causes. 
• 
Consider inpatient care. 
T1DM or 
hyperglycemia 
Grade 3 to 4 
hyperglycemia or 
T1DM (associated 
with metabolic 
acidosis or 
ketonuria) 
Restart in appropriately 
managed clinically and 
metabolically stable 
participants; insulin 
replacement therapy is 
required. 
• 
Initiate insulin replacement 
therapy for participants with 
T1DM. 
 
• 
Monitor participants for 
hyperglycemia or other signs and 
symptoms of diabetes. 
• 
Ensure adequate evaluation (e.g. 
specialist consultation) 
Uveitis 
Grade 2  
Withhold. 
• 
Urgent ophthalmology 
consultation. 
• 
Administer treatment with 
ophthalmic and systemic 
prednisone/methylprednisolone. 
• 
Ensure adequate evaluation (e.g., 
urgent ophthalmology consultation) 
Grade 3 or 4 
Permanently discontinue. 
Other suspected drug 
related imAEs 
Based on severity 
and type of 
reaction  
(Grade 2 or 3) 
Restart dosing when toxicity 
resolves to Grade ≤1. 
Based on severity of AE, administer 
corticosteroids. When controlled, 
taper steroid. 
• 
Ensure adequate evaluation (including 
specialist consultation) to confirm 
etiology and exclude other causes. 
Grade 4 or 
recurrent Grade 3 
Permanently discontinue. 
AE = adverse event; ALT = alanine aminotransferase; AST = aspartate aminotransferase; BP = blood pressure; DRESS = drug reaction with eosinophilia and 
systemic symptoms; GI = gastrointestinal; HLH = hemophagocytic lymphohistiocytosis; HRT = hormone replacement therapy; ICI = immune checkpoint inhibitor; 
imAE = immune-mediated adverse event; IV = intravenous; LFT = liver function test; MRI = magnetic resonance imaging; NCI-CTCAE = National Cancer Institute 
Common Terminology Criteria for Adverse Events; PCR = polymerase chain reaction; PJP= Pneumocystis jiroveci pneumonia; SJS=Stevens-Johnson syndrome; 
SOC = standard of care; T1DM= Type 1 diabetes mellitus; TEN=toxic epidermal necrolysis; ULN=upper limit of normal 
 
 

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Appendix E. Liver Chemistry Monitoring Guidance for Dostarlimab 
Level 1 Monitoring 
If a participant develops elevations in liver enzyme parameters as defined in Table 11, an increased frequency of liver chemistry monitoring 
(i.e., at weekly intervals) will apply. 
Table 11: 
Liver Event Increased Monitoring Criteria (Level 1 Liver Monitoring) 
Criteria 
Actions 
ALT >3x ULN and ≥1.5x baseline value and not 
meeting any Level 2 monitoring criteria, without 
symptoms believed to be related to liver injury or 
hypersensitivity, and who can be monitored 
weekly for 4 weeks 
• 
Notify the Elevation Oncology medical monitor within 24 hours of learning of the abnormality to discuss 
participant safety. 
• 
Participant must return weekly for repeat liver chemistries (ALT, AST, alkaline phosphatase, total bilirubin, 
and INR) until they stabilize (i.e., ALT or AST ≤3x ULN and <1.5x baseline value, and no increases in total 
bilirubin or INR) or return to within baseline or normal limits. 
• 
If, during monitoring, ALT increases to >5x ULN and ≥2x baseline value or remains >3x ULN and 
≥1.5x baseline value for ≥4 weeks, or if total bilirubin increases to ≥2x ULN, refer to Level 2 monitoring 
guidance (Table 12). 
• 
If Level 2 monitoring criteria are not met after 4 weeks of monitoring but any of the monitored liver 
chemistry values (ALT, AST, alkaline phosphatase, total bilirubin, or INR) remain abnormal/above 
baseline, monitor the participant twice monthly until value(s) stabilize or return to within baseline or normal 
limits. Alternatively, the monitoring can return to standard per protocol (if applicable) or stopped when the 
investigator and medical monitor agree that values are stable or no longer significantly abnormal; this may 
require local investigation of potential causes for liver chemistry abnormality. 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; GSK = GlaxoSmithKline; INR = international normalized ratio; ULN = upper limit of normal. 
 
 

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Level 2 Monitoring 
If a participant develops elevations in liver enzyme parameters as defined in Table 12, increased frequency of liver chemistry monitoring 
(i.e., twice weekly) will apply. 
Table 12: 
Liver Event Increased Monitoring Criteria (Level 2 Liver Monitoring) 
Parameter 
Criteria 
ALT absolute 
Both ALT >5x ULN and ≥2x baseline value 
ALT increase 
Both ALT >3x ULN and ≥1.5x baseline value that persists for 4 weeks 
Bilirubina,b 
ALT >3x ULN and total bilirubin ≥2x ULN (for participants with known Gilbert’s syndrome, these criteria only apply if total 
bilirubin ≥2x ULN and direct bilirubin ≥2x ULN and ≥2x baseline value) 
INRb 
ALT >3x ULN and INR >1.5 
Symptomaticc 
Both ALT >3x ULN and ≥1.5x baseline value associated with symptoms (new or worsening) believed to be related to liver 
injury or hypersensitivity 
Required Actions, Monitoring and Follow-up to Assess Causality for Liver Event 
Actions and Monitoring 
Follow-up to Assess Causality of Liver Event 
• 
Report the event to Elevation Oncology within 24 hours 
• 
Complete the liver event form and complete SAE data collection 
tool if the event also meets the criteria for an SAEb 
• 
Perform liver event follow-up to assess causality of liver event 
• 
Monitor the participant liver chemistries (see MONITORING) 
 
MONITORING: 
 
If ALT >3x ULN and total bilirubin ≥2x ULN or INR >1.5: 
• 
Repeat liver chemistries (include ALT, AST, alkaline phosphatase, 
total bilirubin, and INR) and perform liver event follow-up to 
assess liver event causality within 24 hours 
• 
Monitor participants twice weekly until liver chemistries reduce to 
≤3x ULN for ALT, <2x ULN for total bilirubin, or ≤1.5 for INR or 
return to or remain within baseline or normal limits 
• 
A specialist or hepatology consultation is recommended 
 
For all other criteria (total bilirubin <2x ULN and INR ≤1.5): 
• 
Repeat liver chemistries (include ALT, AST, alkaline phosphatase, 
total bilirubin, and INR) and perform liver event follow-up to 
assess causality of liver event within 24-72 hours 
• 
Viral serologyd 
• 
Anti-nuclear antibody, anti-smooth muscle antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative total IgG or gamma globulins 
• 
Serum CPK, LDH, GGT, GLDH, and serum albumin 
• 
Fractionate bilirubin, if total bilirubin ≥2x ULN 
• 
Obtain complete blood count with differential to assess eosinophilia 
• 
Record the appearance or worsening of clinical symptoms of liver injury or 
hypersensitivity on adverse event form 
• 
Record use of concomitant medications on the concomitant medications eCRF 
including acetaminophen, herbal remedies, recreational drugs, and other 
over-the-counter medications 
• 
Record alcohol use in narrative if serious adverse event 
 
If ALT >3x ULN and total bilirubin ≥2x ULN or INR >1.5, obtain the following in 
addition to the assessments listed above: 
• 
Serum acetaminophen adduct assay should be conducted (where available) to assess 
potential acetaminophen contribution to liver injury 
• 
Liver imaging (ultrasound, MRI, or CT) to evaluate liver disease; complete liver 
imaging form 
• 
Liver biopsy may be considered and discussed with local specialist if available, for 
instance: 
o 
When serology raises the possibility of AIH 

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• 
Monitor participant weekly until liver chemistries reduce to 
≤3x ULN and <1.5x baseline value for ALT or return to or remain 
within baseline or normal limits 
o 
When suspected DILI progresses or fails to resolve on withdrawal of study 
intervention 
o 
In participants with acute or chronic atypical presentation. 
 
AIH = autoimmune hepatitis; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CPK = creatine phosphokinase; CT = computed tomography; 
DILI = drug-induced liver injury; eCRF = electronic case report form; GGT = gamma glutamyl transferase; GLDH = glutamate dehydrogenase; 
GSK = GlaxoSmithKline; HBcAb = hepatitis B core antibody; HBsAg = hepatitis B surface antigen; HBV= hepatitis B virus; HCV = hepatitis C virus; 
HDV= hepatitis D virus; Ig = immunoglobulin; INR = international normalized ratio; LDH = lactate dehydrogenase; MRI = magnetic resonance imaging; 
PCR = polymerase chain reaction; PK = pharmacokinetic(s); RNA = ribonucleic acid; SAE = serious adverse event; ULN = upper limit of normal. 
a. 
Serum bilirubin fractionation should be performed if testing is available. Additionally, if serum bilirubin fractionation testing is unavailable, record presence of 
detectable urinary bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury. 
b. All events of ALT >3x ULN and total bilirubin ≥2x ULN (for participants with known Gilbert’s syndrome, these criteria only apply if total bilirubin ≥2x ULN 
and direct bilirubin ≥2x ULN and ≥2x baseline value) or ALT >3x ULN and INR >1.5, which may indicate severe liver injury (possible ‘Hy’s Law’), must be 
reported as an SAE [(excluding studies of hepatic impairment or cirrhosis)]; the INR threshold value stated will not apply to participants receiving 
anticoagulants. 
c. 
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper quadrant pain or tenderness, or jaundice) or 
believed to be related to hypersensitivity (such as fever, rash, or eosinophilia). 
d. 
Includes: Hepatitis A IgM antibody; HBsAg and HBcAb (IgM); HCV RNA; cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or 
if unavailable, obtain heterophile antibody or monospot testing); Hepatitis E IgM antibody, and RNA PCR test. HBV DNA quantification, and HDV antibody 
should be measured if participant is known to be HBsAg and/or HBcAb-positive prior to onset of the liver event or is subsequently found to be HBsAg-positive 
on investigation following the liver event. If hepatitis delta antibody assay cannot be performed, it can be replaced with a PCR of HDV RNA virus (where 
needed and if this is feasible).