A Multicentric Phase 1/2 Trial to Evaluate the Safety and Efficacy of SOT102 as Monotherapy and in Combination With Standard of Care Treatment in Patients With Gastric and Pancreatic Adenocarcinoma
Phase: PHASE1
Conditions: Pancreatic Cancer
Sponsor: SOTIO Biotech a.s.

 
 
 
 
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A multicentric phase 1/2 trial to evaluate the safety and efficacy of SOT102 
as monotherapy and in combination with standard of care treatment in 
patients with gastric and pancreatic adenocarcinoma 
Trial intervention 
SOT102 
Regulatory agency identifier 
numbers 
EUCT number: 2023-504441-31-00 
IND number: 157062 
NCT number: NCT05525286 
Protocol number 
SN201 (CLAUDIO-01) 
Phase 
1/2 
Version 
Amendment 5 
Date 
04Jun2024 
Sponsor 
SOTIO Biotech a.s. 
Legal registered address 
Ceskomoravska 2532/19b 
190 00 Prague 
Czech Republic 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
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SIGNATURES/PROTOCOL APPROVAL AND RELEASE SOTIO 
We, the undersigned, have read this Protocol and agree that it contains all the necessary 
information required for the conduct of this clinical trial. 
 
For SOTIO Biotech a.s: 
 
 
Chief Medical Officer 
See electronic signature 
 
Senior Medical Director 
See electronic signature 
 
Senior Statistician 
See electronic signature 
 
 

Signature Page for VV-TMF-48612 v1.0
Signature Page for VV-TMF-48612 v1.0
Reason for signing: Approved
Name: 
Role: B
Date of signature: 11-Jun-2024 07:34:09
GMT+0000
Reason for signing: Approved
Name: 
Role: S
Date of signature: 11-Jun-2024 09:20:45
GMT+0000
Reason for signing: Approved
Name: 
Role: C
velopment
Date of signature: 11-Jun-2024 09:38:18
GMT+0000

 
 
 
 
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INVESTIGATOR’S DECLARATION 
I have read this Protocol and I agree that it contains all the necessary details for carrying out 
this clinical trial. I agree to personally conduct or supervise the clinical trial as described in 
accordance with the relevant current Protocol and within the time designated. I will only make 
changes after receiving the sponsor’s approval, except when necessary to protect the safety, 
rights, or welfare of patients. 
I verify that I am suitably qualified by education, scientific medical training, and experience to 
conduct the clinical trial. Documentation of my qualifications and professional affiliations are 
contained in my up-to-date curriculum vitae. 
I will provide the Protocol and all information relating to preclinical and previous clinical 
experience (e.g., Investigator’s Brochure) to all associates, colleagues, and staff assisting in the 
conduct of this clinical trial. I will discuss the material with them to ensure that they are fully 
conversant with the Protocol, the medical treatment, and the conduct of the clinical trial, and 
that they will handle the data and information generated in the clinical trial confidentially. I 
agree to ensure that they are informed about their obligations in meeting the investigator’s 
commitments listed in this Investigator’s Declaration, as delegated and applicable to them. 
I agree to personally conduct or supervise the clinical trial in accordance with: i) the current 
version of the Declaration of Helsinki; ii) the current version of International Council for 
Harmonisation (ICH) guidelines on Good Clinical Practice (ICH E6); iii) the moral, ethical, 
and scientific principles that justify medical research; and iv) all relevant national and regional 
laws and regulations relating to clinical trials and the protection of patients of the country in 
which the clinical trial will be performed. 
I will ensure that an institutional review board (IRB) or independent ethics committee (IEC; in 
the United States [US])/ethics committee (EC; in the European Union [EU])/equivalent 
committee (outside the US and EU) that complies with the requirements of national and 
regional legislation and the Declaration of Helsinki, and that follows the recommendations in 
ICH E6, will be responsible for the initial and continuing review and approval of the clinical 
investigation. I also agree to promptly report to the IRB/IEC (in the US)/EC (in the 
EU)/equivalent committee (outside the US and EU) all changes in research activity and all 
unanticipated problems involving risks to patients or others. Additionally, I will not make any 
changes in the research without IRB/IEC (in the US)/EC (in the EU)/equivalent committee 
(outside the US and EU) approval, except where necessary to eliminate apparent immediate 
hazards to patients. 
I agree to inform all patients and associates, colleagues, and staff assisting in the conduct of 
this clinical trial that the trial intervention(s) are being used for investigational purposes, and I 
will ensure that the requirements relating to obtaining informed consent and IRB/IEC (in the 
US)/EC (in the EU)/equivalent committee (outside the US and EU) review and approval are 
met in accordance with national and regional legislation and the Declaration of Helsinki, and 
consistent with the recommendations in ICH E6. 
All patients will be informed that they may withdraw from the clinical trial at their discretion 
at any time. I will use only the information sheet and consent form approved by the sponsor 
and the IRB/IEC (in the US)/EC (in the EU)/equivalent committee (outside the US and EU) 
which has reviewed this clinical trial. 

 
 
 
 
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I will provide the sponsor with any material written by myself (e.g., clinical trial summary) 
which is given to the IRB/IEC (in the US)/EC (in the EU)/equivalent committee (outside the 
US and EU) in support of the application. I agree to maintain adequate and accurate records 
and to make those records available for inspection in accordance with national and regional 
legislation and the Declaration of Helsinki, and consistent with the recommendations in ICH 
E6. I agree to the audit and monitoring procedures that involve verification of clinical trial 
records against the original records by direct access. In case the source documentation and 
clinical trial data are kept electronically, I agree to ensure that these comply with the 
requirements on computerized systems and their validation in line with national and regional 
legislation and recommendations in ICH E6. 
I will retain the trial-related essential documents until the sponsor informs me that these 
documents are no longer needed but no sooner than the requirements in national and regional 
legislation. 
I certify that any laboratory, excluding the central laboratory (laboratories) appointed for the 
clinical trial, in which laboratory parameters will be determined, is subject to regular external 
quality control. 
I agree to report to the sponsor adverse events that occur in the course of the clinical trial in 
accordance with national and regional legislation and the Declaration of Helsinki, and 
consistent with the recommendations in ICH E6. I have read and understand the information in 
the Investigator’s Brochure, including the potential risks and side effects of the trial 
intervention. 
I agree to the collection, processing, transfer, use, and storing of my personal data and details 
relating to my professional activities for the purposes of the clinical trial by the sponsor and/or 
by a delegated party (e.g., a contract research organization). 
I understand that the (electronic) case report forms and other data pertinent to this clinical trial 
are the property of the sponsor and are confidential. I will supply the sponsor with the clinical 
trial data in such a way that the patient’s personal information and identity are protected. 
I agree to comply with all other requirements regarding obligations of clinical investigators and 
with all other pertinent requirements in accordance with national and regional legislation and 
the Declaration of Helsinki. I also agree to follow the recommendations in ICH E6. 
Investigator’s signature: 
__________________________________________________ 
Date:  
 
 
__________________________________________________ 
Printed name:  
 
__________________________________________________ 
Street address: 
 
__________________________________________________ 
Telephone number: 
 
__________________________________________________ 
Other contact information 
Full contact details for each investigational site, the sponsor, and key coordinating and 
operational personnel involved in this clinical trial will be maintained in the Trial Master File 
and in the Investigator Site File. 
 
 

 
 
 
 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES 
DOCUMENT HISTORY 
Version 
Date 
Amendment 5 
04Jun2024 
Amendment 4 
08Mar2024 
Amendment 3 
27Apr2023 
Amendment 2 
01Sep2022 
Amendment FR-2 
22Jun2022 
Amendment BE-2 
26May2022 
Amendment BE-1 
03May2022 
Amendment FR-1 
26Apr2022 
Amendment CZ-1 
01Mar2022 
Amendment 1 
14Jan2022 
1 
23Nov2021 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment 5 
1 
The population of Part A and B was narrowed to 
CLDN18.2-positive patients. Prospective testing from 
biopsy samples for CLDN18.2 expression on tumors was 
added. 
To allow only CLDN18.2-positive patients to 
be enrolled in the trial 
1.1 Synopsis; 1.2 Schema; 1.3.1 Schedule of 
activities Part A; 1.3.3 Schedule of activities Part B 
pancreatic; 1.3.4 Schedule of activities Part C; 1.3.5 
Schedule of Activities Part D; 2.1 Trial rationale; 
4.1 Overall design; 4.1.2 Part A; 4.1.3 Part B; 4.1.4 
Part C; 4.1.5 Part D; 4.2 Scientific rationale for trial 
design; 5.1.1 Inclusion criteria applicable to all trial 
parts; 6.1.3 Investigational medical device; 8.6 
Tumor biopsy; 8.7 Biomarkers 
2 
Planned duration of trial was updated 
To reflect current eligibility criteria and 
planned assessments 
1.1 Synopsis; 4.4 Trial and site start and closure 
3 
For patients ongoing in gastric cohort, assessments have 
been updated to reflect that they are continuing in the trial 
on SoC and no SOT102 will be administered. Eligibility 
criteria have been updated to reflect that no new 
gastric/GEJ cancer patients will be enrolled in the trial.  
SOT102 will not be administered to 
gastric/GEJ cancer patients anymore, nor will 
new patients be enrolled in this cohort - some 
assessments do not need to be made or do not 
need to be made within a related time 
window 
1.3.2 Schedule of activities Part B gastric; 5.1.3 
Inclusion criteria specific to Part B; 5.2.3 Exclusion 
criteria specific to Part B 
4 
Patient rescreening introduced 
To allow patients who are deemed to still 
benefit from trial participation to be 
considered for the trial in situations when 
screening was not possible in the initial 
period 
4.1.2.1 Screening; 4.1.3.1 Screening; 4.1.4.1 
Screening; 4.1.5.1 Screening; 5.4 Screen failures 
5 
Minor wording and punctuation corrections 
To improve clarity and readability  
Throughout the document 

 
 
 
 
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TABLE OF CONTENTS 
SIGNATURES/PROTOCOL APPROVAL AND RELEASE SOTIO ..................................... 2 
SIGNATURES/PROTOCOL 
APPROVAL 
AND 
RELEASE 
COORDINATING 
INVESTIGATOR ...................................................................................................................... 3 
INVESTIGATOR’S DECLARATION ..................................................................................... 4 
PROTOCOL AMENDMENT SUMMARY OF CHANGES .................................................... 6 
TABLE OF CONTENTS ........................................................................................................... 8 
1 
PROTOCOL SUMMARY ............................................................................................... 15 
1.1 
Synopsis ...................................................................................................................... 15 
1.2 
Schema ....................................................................................................................... 19 
1.3 
Schedule of activities .................................................................................................. 20 
1.3.1 
Schedule of activities, Part A (SOT102 monotherapy, dose escalation, 
CLDN18.2-positive) ........................................................................................... 20 
1.3.2 
Schedule of activities, Part B gastric (SOT102 combination with first-line SoC 
treatment, dose escalation, CLDN18.2-agnostic) ............................................... 22 
1.3.3 
Schedule of activities, Part B pancreatic (SOT102 combination with first-line SoC 
treatment, dose escalation, CLDN18.2-positive) ................................................ 23 
1.3.4 
Schedule of activities, Part C (SOT102 monotherapy, cohort expansion, 
CLDN18.2-positive tumors; pancreatic cancer second- or further-line) ............ 25 
1.3.5 
Schedule of activities, Part D pancreatic (SOT102 combination with first-line SoC 
treatment, cohort expansion, CLDN18.2-positive tumors; pancreatic cancer first-
line) ..................................................................................................................... 27 
1.3.6 
PK and ADA sampling (SOT102), Part A and Part B ........................................ 30 
1.3.7 
PK and ADA sampling (SOT102), Part C and Part D ........................................ 32 
2 
INTRODUCTION ............................................................................................................ 33 
2.1 
Trial rationale ............................................................................................................. 33 
2.2 
Background ................................................................................................................ 33 
2.3 
Benefit/risk assessment .............................................................................................. 34 
3 
OBJECTIVES AND ENDPOINTS .................................................................................. 35 
4 
TRIAL DESIGN ............................................................................................................... 38 
4.1 
Overall design ............................................................................................................. 38 
4.1.1 
Dose escalation plan (Part A and Part B)............................................................ 38 
4.1.1.1 
Dose-limiting toxicities definitions............................................................... 41 
4.1.1.2 
Maximum tolerated dose and selection of the recommended phase 2 dose . 42 
4.1.1.3 
Dose escalation meetings .............................................................................. 42 

 
 
 
 
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4.1.1.4 
Safety monitoring.......................................................................................... 42 
4.1.1.4.1 
Part A .................................................................................................. 42 
4.1.1.4.2 
Part B .................................................................................................. 42 
4.1.1.5 
Patient recruitment management ................................................................... 43 
4.1.1.6 
Communication plan ..................................................................................... 43 
4.1.2 
Part A (SOT102 monotherapy, dose escalation)................................................. 43 
4.1.2.1 
Screening period ........................................................................................... 44 
4.1.2.2 
DLT evaluation period .................................................................................. 44 
4.1.2.3 
Continued treatment period........................................................................... 44 
4.1.2.4 
Follow-up period ........................................................................................... 45 
4.1.3 
Part B (SOT102 combined with first-line SoC treatment, dose escalation) ....... 45 
4.1.3.1 
Screening period ........................................................................................... 46 
4.1.3.2 
DLT evaluation period .................................................................................. 46 
4.1.3.3 
Continued treatment period........................................................................... 46 
4.1.3.4 
Follow-up period ........................................................................................... 47 
4.1.4 
Part C (SOT102 monotherapy, cohort expansion) .............................................. 47 
4.1.4.1 
Screening period ........................................................................................... 48 
4.1.4.2 
Treatment period ........................................................................................... 48 
4.1.4.3 
Follow-up ...................................................................................................... 48 
4.1.5 
Part D (SOT102 combined with first-line SoC treatment, cohort expansion) .... 48 
4.1.5.1 
Screening period ........................................................................................... 49 
4.1.5.2 
Treatment period ........................................................................................... 49 
4.1.5.3 
Follow-up period ........................................................................................... 50 
4.2 
Scientific rationale for trial design ............................................................................. 50 
4.3 
Justification for dose .................................................................................................. 50 
4.3.1 
Starting dose and dose escalation steps in Part A ............................................... 50 
4.3.2 
Starting dose and dose escalation steps in Part B ............................................... 51 
4.4 
Trial and site start and closure .................................................................................... 51 
5 
TRIAL POPULATION .................................................................................................... 53 
5.1 
Inclusion criteria ......................................................................................................... 53 
5.1.1 
Inclusion criteria applicable to all trial parts ....................................................... 53 
5.1.2 
Inclusion criteria specific to Part A .................................................................... 55 
5.1.3 
Inclusion criteria specific to Part B ..................................................................... 55 

 
 
 
 
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5.1.4 
Inclusion criteria specific to Part C ..................................................................... 55 
5.1.5 
Inclusion criteria specific to Part D .................................................................... 55 
5.2 
Exclusion criteria ........................................................................................................ 55 
5.2.1 
Exclusion criteria applicable to all trial parts ..................................................... 55 
5.2.2 
Exclusion criteria specific to Part A ................................................................... 57 
5.2.3 
Exclusion criteria specific to Part B.................................................................... 57 
5.2.4 
Exclusion criteria specific to Part C.................................................................... 57 
5.2.5 
Exclusion criteria specific to Part D ................................................................... 57 
5.3 
Lifestyle considerations .............................................................................................. 58 
5.3.1 
Meals and dietary restrictions ............................................................................. 58 
5.3.2 
Contraception ...................................................................................................... 58 
5.3.3 
Use in nursing women ........................................................................................ 58 
5.4 
Screen failures ............................................................................................................ 58 
5.5 
Criteria for temporarily delaying enrollment/administration of trial intervention ..... 58 
6 
TRIAL INTERVENTIONS AND CONCOMITANT THERAPY .................................. 60 
6.1 
Trial interventions administered ................................................................................. 60 
6.1.1 
SOT102 (all trial parts) ....................................................................................... 60 
6.1.2 
First-line SoC treatment (Part B and Part D) ...................................................... 60 
6.1.2.1 
Nab-paclitaxel/gemcitabine .......................................................................... 60 
6.1.2.2 
mFOLFOX6 and nivolumab ......................................................................... 60 
6.1.3 
Investigational medical device ............................................................................ 61 
6.2 
Preparation, handling, storage, accountability ........................................................... 61 
6.3 
Measures to minimize bias: randomization and blinding ........................................... 61 
6.4 
Trial intervention compliance .................................................................................... 61 
6.5 
Dose modification ...................................................................................................... 62 
6.5.1 
Dose modification and toxicity management for SOT102 ................................. 62 
6.5.2 
Dose modification and toxicity management for first-line SoC treatment ......... 62 
6.6 
Continued access to trial intervention after the end of the trial .................................. 63 
6.7 
Treatment of overdose ................................................................................................ 63 
6.8 
Concomitant therapy .................................................................................................. 63 
6.8.1 
Rescue medication and supportive care .............................................................. 63 
6.8.2 
Drug-drug interaction potential........................................................................... 63 
6.8.3 
Medications requiring special caution ................................................................ 64 

 
 
 
 
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6.8.3.1 
mFOLFOX6 .................................................................................................. 64 
6.8.3.2 
Nab-paclitaxel ............................................................................................... 64 
7 
DISCONTINUATION 
OF 
TRIAL 
INTERVENTION 
AND 
PATIENT 
DISCONTINUATION/WITHDRAWAL................................................................................ 65 
7.1 
Discontinuation of trial intervention .......................................................................... 65 
7.2 
Patient discontinuation/withdrawal from the trial ...................................................... 65 
7.3 
Lost to follow-up ........................................................................................................ 65 
8 
TRIAL ASSESSMENTS AND PROCEDURES ............................................................. 67 
8.1 
Efficacy assessments .................................................................................................. 67 
8.1.1 
Radiologic evaluation of disease ........................................................................ 67 
8.1.2 
Quality of life assessments (only in Part C and Part D) ..................................... 68 
8.1.3 
Survival information assessments (only in Part C and Part D) ........................... 68 
8.2 
Safety assessments ..................................................................................................... 68 
8.2.1 
Physical examinations, body height, weight, and surface area, ECOG 
performance status .............................................................................................. 68 
8.2.2 
Vital signs ........................................................................................................... 69 
8.2.3 
Special assessments on treatment days ............................................................... 69 
8.2.3.1 
Cycle 1 day 1 ................................................................................................ 69 
8.2.3.2 
Cycle 2 and onwards ..................................................................................... 69 
8.2.4 
Electrocardiography ............................................................................................ 69 
8.2.5 
Clinical safety laboratory assessments ................................................................ 69 
8.2.6 
Left ventricular ejection fraction ........................................................................ 70 
8.2.7 
Esophagogastroduodenoscopy ............................................................................ 70 
8.3 
Adverse events, serious adverse events, and other safety reporting........................... 70 
8.3.1 
Definitions........................................................................................................... 70 
8.3.1.1 
Adverse events .............................................................................................. 70 
8.3.1.2 
Serious adverse events .................................................................................. 70 
8.3.1.3 
Excluded events ............................................................................................ 71 
8.3.1.4 
Severity/intensity vs. seriousness.................................................................. 71 
8.3.2 
Time period and frequency for collecting AE, SAE, and other reportable safety 
event information ................................................................................................ 71 
8.3.3 
Method of detecting AEs and SAEs ................................................................... 72 
8.3.4 
Follow-up of AEs and SAEs ............................................................................... 72 
8.3.5 
Regulatory reporting requirements for SAEs ..................................................... 72 

 
 
 
 
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8.3.6 
Pregnancy ............................................................................................................ 72 
8.3.7 
Assessing AEs ..................................................................................................... 73 
8.3.7.1 
Causality ....................................................................................................... 73 
8.3.7.2 
Severity/intensity .......................................................................................... 73 
8.3.8 
Reporting by the investigational site................................................................... 74 
8.3.8.1 
Adverse events .............................................................................................. 74 
8.3.8.2 
Documenting in eCRFs ................................................................................. 74 
8.3.8.3 
Immediately reportable events ...................................................................... 75 
8.3.8.4 
Report forms ................................................................................................. 75 
8.4 
Pharmacokinetics ........................................................................................................ 76 
8.5 
Genetics ...................................................................................................................... 76 
8.6 
Tumor biopsy ............................................................................................................. 76 
8.7 
Biomarkers ................................................................................................................. 77 
8.8 
Immunogenicity assessments ..................................................................................... 77 
8.9 
Health economics ....................................................................................................... 77 
9 
STATISTICAL CONSIDERATIONS ............................................................................. 78 
9.1 
Statistical hypotheses ................................................................................................. 78 
9.2 
Analysis sets ............................................................................................................... 78 
9.2.1 
Safety population ................................................................................................ 78 
9.2.2 
PK population ..................................................................................................... 78 
9.2.3 
DLT-evaluable patients (defined for Part A and Part B only) ............................ 78 
9.2.4 
Efficacy population ............................................................................................. 78 
9.3 
Statistical analyses ...................................................................................................... 78 
9.3.1 
Part A (SOT102 monotherapy, dose escalation) and Part B (SOT102 combination 
with first-line SoC treatment, dose escalation) ................................................... 78 
9.3.1.1 
Primary endpoint analysis ............................................................................. 78 
9.3.1.2 
Secondary endpoints analysis ....................................................................... 79 
9.3.1.2.1 
Safety analyses ................................................................................... 79 
9.3.1.2.1.1 Treatment-emergent AEs ................................................................. 79 
9.3.1.2.1.2 Laboratory values and vital signs ..................................................... 79 
9.3.1.2.2 
Efficacy analyses ................................................................................ 79 
9.3.2 
Part C (SOT102 monotherapy, cohort expansion) .............................................. 79 
9.3.2.1 
Primary endpoint analysis ............................................................................. 79 
9.3.2.1.1.1 Objective response rate .................................................................... 79 

 
 
 
 
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9.3.2.2 
Secondary endpoints analysis ....................................................................... 80 
9.3.2.2.1 
Safety analyses ................................................................................... 80 
9.3.2.2.1.1 Treatment-emergent AEs ................................................................. 80 
9.3.2.2.1.2 Laboratory values and vital signs ..................................................... 80 
9.3.2.2.2 
Efficacy analyses ................................................................................ 80 
9.3.2.2.2.1 Duration of response ........................................................................ 80 
9.3.2.2.2.2 Progression-free survival .................................................................. 81 
9.3.2.2.2.3 Overall survival ................................................................................ 81 
9.3.2.2.2.4 Clinical benefit rate .......................................................................... 81 
9.3.3 
Part D (SOT102 combined with first-line SoC treatment, cohort expansion) .... 81 
9.4 
Interim analysis .......................................................................................................... 82 
9.5 
Sample size determination .......................................................................................... 82 
9.5.1 
Part A (SOT102 monotherapy, dose escalation)................................................. 82 
9.5.2 
Part B (SOT102 combined with first-line SoC treatment, dose escalation) ....... 82 
9.5.3 
Part C (SOT102 monotherapy, cohort expansion) and Part D (SOT102 
combination with first-line SoC treatment, cohort expansion) ........................... 82 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ... 83 
10.1 Appendix 1: Regulatory, ethical, and trial oversight considerations ......................... 83 
10.1.1 Regulatory and ethical considerations ................................................................ 83 
10.1.2 Financial disclosure ............................................................................................ 84 
10.1.3 Informed consent process ................................................................................... 84 
10.1.4 Data protection .................................................................................................... 85 
10.1.5 Organizational structure of the trial .................................................................... 86 
10.1.6 Dissemination of clinical trial data ..................................................................... 87 
10.1.7 Risk management and quality assurance ............................................................ 87 
10.1.7.1 Data quality assurance .................................................................................. 87 
10.1.8 Trial monitoring, access to source documentation, and data retention ............... 87 
10.1.9 Publication policy ............................................................................................... 88 
10.1.10 Committees ......................................................................................................... 88 
10.1.10.1 Independent committees ............................................................................... 88 
10.1.10.1.1 Data monitoring committee ................................................................ 88 
10.1.11 Future research .................................................................................................... 89 
10.2 Appendix 2: Hy’s law ................................................................................................. 89 
10.3 Appendix 3: Cockcroft-Gault formula ....................................................................... 89 

 
 
 
 
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10.4 Appendix 4: Laboratory parameters to be assessed ................................................... 89 
10.4.1 Coagulation ......................................................................................................... 89 
10.4.2 Hematology ......................................................................................................... 89 
10.4.3 Clinical chemistry ............................................................................................... 90 
10.4.4 Urinalysis ............................................................................................................ 90 
10.5 Appendix 5: List of medications requiring special caution ........................................ 92 
10.6 Appendix 6: Abbreviations ........................................................................................ 96 
10.7 Appendix 7: Protocol Amendment history ................................................................. 99 
10.7.1 Amendment 4 (08Mar2024): Protocol changes implemented ............................ 99 
10.7.2 Amendment 3 (27Apr2023): Protocol changes implemented .......................... 102 
10.7.3 Amendment FR-3 (01Sep2022): Protocol changes implemented .................... 103 
10.7.4 Amendment 2 (01Sep2022): Protocol changes implemented ........................... 106 
10.7.5 Amendment FR-2 (22Jun2022): Protocol changes implemented ..................... 111 
10.7.6 Amendment BE-2 (26May2022): Protocol changes implemented ................... 112 
10.7.7 Amendment BE-1 (03May2022): Protocol changes implemented ................... 113 
10.7.8 Amendment FR-1 (26Apr2022): Protocol changes implemented .................... 117 
10.7.9 Amendment CZ-1 (01Mar2022): Protocol changes implemented .................... 123 
10.7.10 Amendment 1 (14Jan2022): Protocol changes implemented ........................... 124 
10.8 Appendix 8: Country-specific requirements/differences ......................................... 128 
11 REFERENCES ............................................................................................................... 129 
LIST OF IN-TEXT FIGURES 
Figure 4.1: Dose escalation flowchart for Part A and Part B (staggered dosing and 3+3 design)
.................................................................................................................................................. 40 
Figure 4.2: Part A: SOT102 dosing schedule .......................................................................... 44 
Figure 4.4: Part B pancreatic: SOT102 and first-line SoC treatment dosing schedule ............ 46 
Figure 4.5: Part C: SOT102 dosing schedule........................................................................... 48 
Figure 4.7: Part D pancreatic: SOT102 and first-line SoC treatment dosing schedule ........... 49 
 
 

 
 
 
 
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1 PROTOCOL SUMMARY 
1.1 Synopsis 
Full trial title 
A multicentric phase 1/2 trial to evaluate the safety and efficacy of 
SOT102 as monotherapy and in combination with standard of care 
treatment in patients with gastric and pancreatic adenocarcinoma 
Regulatory agency 
identifier numbers 
EUCT number: 2023-504441-31-00 
IND number: 157062 
NCT number: NCT05525286 
Rationale 
CLDN18.2, splice variant 2 of claudin 18, represents a potentially 
attractive tumor-associated antigen. In order to make use of the 
exclusive expression of CLDN18.2 in gastric and pancreatic cells and 
the fact that transient gastrointestinal toxicity is a manageable adverse 
event (AE), SOTIO developed SOT102, an antibody-drug conjugate 
targeting CLDN18.2 with the anthracycline 
 as cytotoxic moiety, 
for the treatment of pancreatic adenocarcinoma. 
The original intention of the trial was to investigate its objectives in 
two indications - gastric/GEJ cancer and pancreatic cancer. Following 
a reassessment of the benefit/risk ratio, it was decided by the sponsor 
to halt the clinical development in gastric/GEJ cancer for the time 
being and proceed only with pancreatic cancer. For more details see 
the IB. 
Objectives and 
endpoints 
Part A and Part B 
Primary 
• To determine the maximum tolerated dose (MTD) and 
recommended phase 2 dose (RP2D) of SOT102 given as 
monotherapy and in combination with first-line standard of care 
(SoC) treatment. MTD is defined as the highest dose level tested 
below the dose level associated with ≥33% of dose-limiting 
toxicity (DLT)-evaluable patients experiencing DLT. The RP2D 
will be selected based on integrated evaluation of the totality of 
clinical and preclinical data, for all dose levels tested. 
Secondary 
• To assess the safety and tolerability of SOT102 in monotherapy 
and in combination with first-line SoC treatment by the 
occurrence of DLTs, occurrence of treatment-emergent AEs 
(TEAEs), SOT102-related AEs, serious AEs (SAEs), AEs leading 
to premature discontinuation of SOT102, deaths, or clinical 
laboratory test abnormalities 
• To characterize the pharmacokinetics (PK) of total SOT102, 
conjugated SOT102, 
 
 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
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• To explore evidence of SOT102 activity in monotherapy and in 
combination with first-line SoC treatment in individual patients 
by anecdotal tumor response per Response Evaluation Criteria in 
Solid Tumors (RECIST) 1.1 by type and CLDN18.2 expression 
• To explore whether patients develop any antibodies against 
SOT102 by the number of patients with detected antibodies 
against any part of SOT102 
Part C and Part D 
Primary 
• To assess the efficacy of SOT102 in monotherapy and in 
combination with first-line SoC treatment by objective response 
rate 
Secondary 
• To evaluate additional measures of efficacy of SOT102 in 
monotherapy and in combination with first-line SoC treatment by 
duration of response, progression-free survival per RECIST 1.1, 
clinical benefit rate per RECIST 1.1 (Part C only), overall survival 
• To assess the safety and tolerability of SOT102 in monotherapy 
and in combination with first-line SoC treatment by the 
occurrence of TEAEs, SOT102-related AEs, SAEs, AEs leading 
to premature discontinuation of SOT102, deaths, or clinical 
laboratory test abnormalities 
• To assess quality of life (QoL) after treatment with SOT102 in 
monotherapy and in combination with first-line SoC treatment by 
assessment of global and disease-specific QoL by patient-
reported questionnaires EORTC QLQ-C30 and EORTC QLQ-
PAN26 for patients with pancreatic cancer 
• To characterize the PK of total SOT102, conjugated SOT102, 
 
 
• To explore whether patients develop any antibodies against 
SOT102 by the number of patients with detected antibodies 
against any part of SOT102 
Exploratory 
• To assess the relationship between the intensity of CLDN18.2 
expression and clinical outcome 
Trial design 
SN201 (CLAUDIO-01) is a multi-modular clinical trial in patients 
with pancreatic adenocarcinoma whose tumor expresses CLDN18.2 
and in ongoing patients with gastric adenocarcinoma or 
adenocarcinoma of the gastroesophageal junction (GEJ), who were 
enrolled in the trial prior to this Protocol Amendment and are allowed 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 17 of 131 
to continue SoC therapy until criteria for discontinuation the SoC 
therapy are met. The trial combines dose finding of SOT102 in 
monotherapy (Part A) and in combination with first-line standard of 
care (SoC) treatment (Part B), followed by respective expansion 
cohorts (Part C in monotherapy, Part D in combination with first-line 
SoC treatment). The SoC treatment for pancreatic cancer will be nab-
paclitaxel with gemcitabine. The SoC treatment for gastric/GEJ 
cancer is modified oxaliplatin + leucovorin + 5-fluorouracil 
containing chemotherapy regimen (mFOLFOX6) with nivolumab. 
Trial population 
Part A 
Patients with histologically or cytologically confirmed evidence of 
gastric/GEJ or CLDN18.2-positive pancreatic adenocarcinoma that is 
advanced or metastatic, who received and/or have been determined to 
be intolerant of all standard of care therapy known to confer clinical 
benefit 
Part B (separate cohorts for gastric/GEJ and pancreatic cancer) 
• Gastric/GEJ adenocarcinoma: Patients with histologically or 
cytologically confirmed evidence of advanced or metastatic 
gastric/GEJ adenocarcinoma with human epidermal growth factor 
receptor 2 (HER2)-negative tumors, who had no earlier treatment 
for advanced, systemic disease 
• Pancreatic adenocarcinoma: Patients with histologically or 
cytologically confirmed evidence of advanced or metastatic 
CLDN18.2-positive pancreatic adenocarcinoma, who had no 
earlier treatment for advanced, systemic disease 
Part C 
• Pancreatic adenocarcinoma: Patients with CLDN18.2-positive 
tumors who received one or more prior lines of systemic therapy 
Part D 
• Pancreatic adenocarcinoma: Patients with CLDN18.2-positive 
tumors and no prior systemic treatment for advanced disease 
Interventions 
SOT102 will be given once every 14 days via the intravenous route 
over 45 (±15) minutes. 
Patients will receive premedication with corticosteroids (4 mg 
dexamethasone twice daily) the day before, the day of (at least one 
hour prior), and the day after each SOT102 administration. 
Nab-paclitaxel (125 mg/m2) will be given as a 30- to 40-minute 
infusion followed by gemcitabine (1000 mg/m2) given as a 30-minute 
infusion on days 1, 8, and 15. This treatment will be repeated every 
28 days. 
For patients in Part B gastric/GEJ cohort who are continuing on SoC 
therapy, nivolumab (240 mg) is given as a 30-minute infusion 
followed by oxaliplatin (85 mg/m2) given as a 2-hour infusion and 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 18 of 131 
leucovorin (400 mg/m2) given as a 30-minute infusion, followed by  
a 5-fluorouracil bolus of 400 mg/m2 followed by 2400 mg/m2  
5-fluorouracil given as a 46-hour continuous infusion (mFOLFOX6). 
This treatment is repeated every 14 days. 
Ethical 
considerations 
Based on preclinical toxicology and efficacy studies, it is assumed 
that the clinical benefits of SOT102 will outweigh the potential risks. 
More detailed information about the known and anticipated benefits 
and risks and potential AEs that could be associated with the 
administration of SOT102 may be found in the IB. 
Trial duration 
It is expected that active enrollment duration will be 30 months in Part 
A, 14 months in Part B, 18 months in Part C, and 18 months in Part 
D. Patients who will respond to therapy will continue with treatment 
until any of the criteria for treatment discontinuation are met. The 
planned overall trial duration is approximately 6 years. The trial will 
end when the last patient completes the last visit or procedure, 
including follow-up calls. 
Estimated sample 
size 
Part A: 55 patients 
Part B: 32 patients 
Part C and Part D: 40 patients in each part 
Site distribution 
Multi-site and multi-regional 
Statistical 
considerations 
Each trial part will be analyzed separately following its objectives. 
Each indication (cohort) in Part B will be analyzed separately. 
The analyses will be descriptive. No formal testing of statistical 
hypotheses is planned in this open-label, single-arm trial. 
Committees 
Independent committees 
A data monitoring committee will be established for trial Part C and 
Part D to safeguard the interest and safety of the patients participating 
in the trial and to provide independent review and assessment of the 
available data in a systematic manner. 
 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
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1.2 Schema 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
DL1 in Part A =  
DL1 in Part B 
Note: In Part B and Part D, the patient must not have prior therapies in metastatic setting 
*Only patients with gastric/ GEJ cancer (gastric B) enrolled in the trial prior to this Protocol Amendment are allowed to continue SoC therapy in the trial until SoC therapy 
discontinuation criteria are met. 
DLn, dose level number; GEJ, gastroesophageal junction; mFOLFOX6, modified FOLFOX6; MTD, maximum tolerated dose; RP2D, recommended phase 2 dose; SoC, standard of care 
Part C (SOT102 monotherapy, cohort expansion at 
the monotherapy RP2D identified in Part A, 
CLDN18.2-positive) 
 
‒ Second+ line pancreatic cancer (pancreatic C) 
 
Estimated sample size: 40 patients 
SAFE
SAFE
DL1 
DL2 
MTD/RP2D 
Part B (SOT102 and first-line SoC, dose escalation) 
 
‒ First-line CLDN18.2-agnostic gastric/GEJ cancer (gastric B); SoC: mFOLFOX6 and 
nivolumab* 
‒ First-line CLDN18.2-positive pancreatic cancer (pancreatic B); SoC: Nab-
paclitaxel/gemcitabine 
 
d
l
Part D (SOT102 and first-line SoC, cohort expansion  
at the combination RP2D identified in Part B,  
CLDN18.2-positive) 
 
‒ First-line pancreatic cancer (pancreatic D);  
SoC: Nab-paclitaxel/gemcitabine 
 
Estimated sample size: 40 patients 
Part A (SOT102 monotherapy, dose escalation) 
 
‒ Locally advanced/metastatic gastric/GEJ (CLDN18.2-agnostic) or 
pancreatic (CLDN18.2-positive) cancer 
 
Estimated sample size: 55 patients 
MTD/RP2D  
SAFE
SAFE
SAFE
SAFE
SAFE
DL1 
DL2 
DL3 
DL5 
DL4 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 20 of 131 
1.3 Schedule of activities 
1.3.1 
Schedule of activities, Part A (SOT102 monotherapy, dose escalation, CLDN18.2-positive) 
Visit 
Screening 
Day -1 
of each 
14-day 
cycle 
Day 1a 
of each 14-day cycle 
Day 2 
of each 
14-day 
cycle 
Day 8 
(±1 day) 
of each 14-day 
cycle 
Follow-up 
21 days 
before day 
1 of cycle 1 
Within 21 days 
before day 1 of 
cycle 1 
30 (+5) days after the last dose 
of SOT102 
Every 6 weeks (±2 weeks) until 
disease progression or start of 
new anticancer therapy 
Informed consent1 
X 
 
 
 
 
 
 
 
Demography2 
 
X 
 
 
 
 
 
 
Cancer3 and medical history 
 
X 
 
 
 
 
 
 
Height 
 
X 
 
 
 
 
 
 
Pregnancy test  
 
X (blood)4 
 
Every other cycle before SOT102 
administration (urine or blood) 
 
 
X 
 
Physical examination 
 
X 
 
X5 
 
 
X 
 
Body weight and body surface area 
 
X 
 
X5 
 
 
X 
 
Vital signs6 
 
X 
 
X6 
 
X 
X 
 
SaO2 
 
X 
 
X12 
 
 
X 
 
Clinical chemistry 
 
X4 
 
X5,17 
 
X 
X 
 
Hematology 
 
X4 
 
X5,17 
 
X 
X 
 
Coagulation (Quick) 
 
X4 
 
X5,17 
 
 
X 
 
Immunogenicity 
 
 
 
X5,7 
 
 
X 
 
Urinalysis8 
 
X4 
 
X5,17 
 
X 
X 
 
Creatinine clearance9 
 
X4 
 
X 
 
X 
X 
 
HIV, hepatitis B 
 
 
 
X12 (HIV, HBV-positive patients 
only) 
 
 
 
 
ECG 
 
X 
 
X5,10,12 
 
 
X 
 
LVEF11 
 
X14 
 
Every 2 months (±2 weeks) 
 
 
X 
 
Esophagogastroduodenoscopy 
 
X14 
 
X12 
 
 
 
 
ECOG performance status 
 
X 
 
X 
 
X 
X 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 21 of 131 
Visit 
Screening 
Day -1 
of each 
14-day 
cycle 
Day 1a 
of each 14-day cycle 
Day 2 
of each 
14-day 
cycle 
Day 8 
(±1 day) 
of each 14-day 
cycle 
Follow-up 
21 days 
before day 
1 of cycle 1 
Within 21 days 
before day 1 of 
cycle 1 
30 (+5) days after the last dose 
of SOT102 
Every 6 weeks (±2 weeks) until 
disease progression or start of 
new anticancer therapy 
Tumor tissue or cytology sample 
(FFPE blocks) or unstained slides 
from archival biopsy or fresh biopsy 
X18 
 
 
 
 
 
 
 
Tumor assessment (CT, MRI)13 
 
X14 
 
Every 6 weeks (±2 weeks) after cycle 1 day 1 
Dexamethasone administration 
 
 
X 
X5 
X 
 
 
 
SOT102 administration15 
 
 
 
X 
 
 
 
 
AEs 
 
X 
 
X 
 
X 
X 
X16 
Concomitant medication/non-drug 
therapies 
 
X 
 
X 
 
X 
X 
X16 
Blood and urine for pharmacokinetic 
studies 
 
 
 
X7 
 
 
 
 
a. D1 is the day of SOT102 administration. Patients may be hospitalized for 24 hours on day 1 of cycle 1, cycle 3, and cycle 5 for observation of AEs and PK sampling 
1. No trial-specific procedures are to be performed prior to ICF signature 
2. Demography includes the collection of information on age at screening, gender, race, and ethnicity 
3. Histology/cytology, initial diagnosis date, details about previous systemic and non-systemic treatment together with the associated disease response and date of last disease progression, and any prior mutations/genetic 
analysis 
4. To be done ≤ 7 days prior to day 1 of cycle 1 
5. Before SOT102 administration in each cycle 
6. Vital signs include body temperature, blood pressure (systolic and diastolic, after ≥15 minutes of rest), and heart rate. To be measured before SOT102 administration, 15 (±5) minutes after the end of SOT102 infusion 
and 60 (±5) minutes after the end of SOT102 infusion. 
7. As specified in section 1.3.6 
8. Urine analysis laboratory test other than dipstick must be performed. Entry limit at screening is grade 1 proteinuria (<1 g/24 hours). A test will be performed prior to each day 1 of each cycle and in case of ≥100 
mg/dL proteinuria, a 24-hour urine analysis will have to be performed (prior to the start of SOT102 treatment) to document 24-hour proteinuria levels. 
9. From serum creatinine, calculated by the Cockcroft-Gault formula; prior to SOT102 administration 
10. Within 15 minutes after the end of SOT102 infusion in each cycle; additionally, 24 (±2) hours after the end of SOT102 infusion in cycle 1 and cycle 3 
11. Using either echocardiography or nuclear medicine methodology (MUGA scan). However, the method chosen needs to stay the same throughout the trial. 
12. As clinically indicated 
13. Until disease progression or until the start of a new anticancer therapy. CT will focus on the chest, abdomen, and pelvis. 
14. Assessments obtained prior the ICF signature as a part or standard of care/routine practice can be used for screening and trial purposes, provided the timelines for screening and cycle 1 day 1 are met 
15. Time to be recorded; starting from cycle 6, SOT102 can be administered on day 1 ±1 day 
16. Applicable only for AEs considered as having a suspected causal relationship to SOT102 per the investigator’s judgment 
17. Starting from cycle 2, safety laboratory samples can be collected 1 day early 
18. Refer to section 8.6 
 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
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1.3.2 
Schedule of activities, Part B gastric (SOT102 combination with first-line SoC treatment, dose escalation, CLDN18.2-agnostic) 
Visit 
Day 1 
Of each 14-day SoC cycle 
Day 8  
(±1 day) 
Of each 14-day SoC cycle 
Follow-up 
Every 6 weeks (±2 weeks) until disease progression or start of new 
anticancer therapy 
Pregnancy test 
Every other cycle (urine or blood)1 
 
 
Physical examination 
X1 
 
 
Body weight and body surface area 
X1 
 
 
Vital signs2 
X2 
X 
 
SaO2 
X7 
 
 
Clinical chemistry 
X1,10 
 
 
Hematology 
X1,10 
X 
 
Coagulation (Quick) 
X1,10 
 
 
Immunogenicity 
X1,3 
 
 
Urinalysis 
X1,10 
 
 
Creatinine clearance4 
X 
 
 
HIV, hepatitis B 
X6 (HIV, HBV-positive patients only) 
 
 
TSH 
Every 6 weeks (±2 weeks), otherwise as per note 6 
 
ECG 
X6 
 
 
LVEF5 
Every 2 months (±2 weeks) 
 
 
Esophagogastroduodenoscopy 
X6 
 
 
ECOG performance status 
X 
X 
 
Tumor assessment (CT, MRI)7 
Every 6 weeks (±2 weeks) after cycle 1 day 1 
mFOLFOX6 and nivolumab administration8 
X 
 
 
AEs 
X 
X 
X9 
Concomitant medication/non-drug therapies 
X 
X 
X9 
Blood and urine for pharmacokinetic studies 
X3 
 
 
1. To be measured in each cycle 
2. Vital signs include body temperature, blood pressure (systolic and diastolic, after ≥15 minutes of rest), and heart rate. To be measured in each cycle. 
3. As specified in section 1.3.6 
4. From serum creatinine, calculated by the Cockcroft-Gault formula 
5. Using either echocardiography or nuclear medicine methodology (MUGA scan). However, the method chosen needs to stay the same throughout the trial. 
6. As clinically indicated 
7. Until disease progression or until the start of a new anticancer therapy. CT will focus on the chest, abdomen, and pelvis. 
8. Time to be recorded; starting from cycle 6, SOT102 and/or first-line SoC treatment can be administered on day 1 ±1 day 
9. Applicable only for AEs considered as having a suspected causal relationship to SOT102 per the investigator’s judgment 
10. Starting from cycle 2, safety laboratory samples can be collected 1 day early 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 23 of 131 
1.3.3 
Schedule of activities, Part B pancreatic (SOT102 combination with first-line SoC treatment, dose escalation, CLDN18.2-positive) 
Visit 
Screening 
Day -1 
of each 
28-day 
SoC 
cycle 
Day 1a,b 
Of each 28-day SoC cycle 
Day 2 
of each 
28-day 
SoC 
cycle 
Day 8 
Of each 
28-day 
SoC 
cycle 
(±1 day) 
Day 15b 
Of each 28-day 
SoC cycle 
(±1 day) 
Day 21  
Of each 28-
day SoC 
cycle 
(±1 day) 
Follow-up 
21 days 
before 
day 1 of 
cycle 1 
Within 21 
days before 
day 1 of 
cycle 1 
30 (+5) 
days after 
the last dose 
of SOT102 
Every 8 weeks (±2 
weeks) until disease 
progression or start of 
new anticancer therapy 
Informed consent1 
X 
 
 
 
 
 
 
 
 
 
Demography2 
 
X 
 
 
 
 
 
 
 
 
Cancer3 and medical history 
 
X 
 
 
 
 
 
 
 
 
Height 
 
X 
 
 
 
 
 
 
 
 
Pregnancy test 
 
X (blood) 4 
 
Each cycle (urine or blood)5 
 
 
 
 
X 
 
Physical examination 
 
X 
 
X5 
 
 
X 
 
X 
 
Body weight and body surface area 
 
X 
 
X5 
 
 
X (weight only)  
 
X 
 
Vital signs6 
 
X 
 
X6 
 
X 
X6 
X 
X 
 
SaO2 
 
X 
 
X12 
 
 
 
 
X 
 
Clinical chemistry 
 
X4 
 
X5,17 
 
X 
X5,17 
X 
X 
 
Hematology 
 
X4 
 
X5,17 
 
X 
X5,17 
X 
X 
 
Coagulation (Quick) 
 
X4 
 
X5,17 
 
 
 
 
X 
 
Immunogenicity 
 
 
 
X5,7 
 
 
 
 
X 
 
Urinalysis8 
 
X4 
 
X5,17 
 
X 
X5,17 
X 
X 
 
Creatinine clearance9 
 
X4 
 
X 
 
X 
X 
X 
X 
 
HIV, hepatitis B 
 
 
 
X12 (HIV, HBV-positive patients only) 
 
 
 
 
 
 
ECG 
 
X 
 
X5,10,12 
 
 
X5,10,12 
 
X 
 
LVEF11 
 
X14 
 
Every 2 months (±2 weeks) 
 
 
 
 
X 
 
Esophagogastroduodenoscopy 
 
X14 
 
X12 
 
 
 
 
 
 
ECOG performance status 
 
X 
 
X 
 
X 
X 
X 
X 
 
Tumor tissue or cytology sample (FFPE blocks) or 
unstained slides from archival biopsy or fresh biopsy 
X19 
 
 
 
 
 
 
 
 
 
Tumor assessment (CT, MRI)13 
 
X14 
 
Every 8 weeks (±2 weeks) after cycle 1 day 1 
Dexamethasone administration 
 
 
X 
X5 
X 
 
X18 
 
 
 
SOT102 administration15 
 
 
 
X 
 
 
X 
 
 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 24 of 131 
Visit 
Screening 
Day -1 
of each 
28-day 
SoC 
cycle 
Day 1a,b 
Of each 28-day SoC cycle 
Day 2 
of each 
28-day 
SoC 
cycle 
Day 8 
Of each 
28-day 
SoC 
cycle 
(±1 day) 
Day 15b 
Of each 28-day 
SoC cycle 
(±1 day) 
Day 21  
Of each 28-
day SoC 
cycle 
(±1 day) 
Follow-up 
21 days 
before 
day 1 of 
cycle 1 
Within 21 
days before 
day 1 of 
cycle 1 
30 (+5) 
days after 
the last dose 
of SOT102 
Every 8 weeks (±2 
weeks) until disease 
progression or start of 
new anticancer therapy 
Nab-paclitaxel/gemcitabine administration15 
 
 
 
X 
 
X 
X 
 
 
 
AEs 
 
X 
 
X 
 
X 
X 
X 
X 
X16 
Concomitant medication/non-drug therapies 
 
X 
 
X 
 
X 
X 
X 
X 
X16 
Blood and urine for pharmacokinetic studies 
 
 
 
X7 
 
 
 
 
 
 
a. Patients may be hospitalized for 24 hours on day 1 of cycle 1, cycle 3, and cycle 5 for observation of AEs and PK sampling 
b. D1 and D15 are the days of SOT102 administration 
1. No trial-specific procedures are to be performed prior to ICF signature 
2. Demography includes the collection of information on age at screening, gender, race, and ethnicity 
3. Histology/cytology, initial diagnosis date, details about previous systemic and non-systemic treatment together with the associated disease response and date of last disease progression, and any prior mutations/genetic 
analysis 
4. To be done ≤ 7 days prior to day 1 of cycle 1 
5. Before SOT102 administration in each cycle 
6. Vital signs include body temperature, blood pressure (systolic and diastolic, after ≥15 minutes of rest), and heart rate. To be measured before SOT102 administration, 15 (±5) minutes after the end of SOT102 infusion 
and 60 (±5) minutes after the end of SOT102 infusion. 
7. As specified in section 1.3.6 
8. Urine analysis laboratory test other than dipstick must be performed. Entry limit at screening is grade 1 proteinuria (<1 g/24 hours). A test will be performed prior to each day 1 of each cycle and in case of ≥100 
mg/dL proteinuria, a 24-hour urine analysis will have to be performed (prior to the start of SOT102 treatment) to document 24-hour proteinuria levels. 
9. From serum creatinine, calculated by the Cockcroft-Gault formula; prior to SOT102 administration 
10. Within 15 minutes after the end of SOT102 infusion in each cycle; additionally, 24 (±2) hours after the end of SOT102 infusion in cycle 1 and cycle 3 
11. Using either echocardiography or nuclear medicine methodology (MUGA scan). However, the method chosen needs to stay the same throughout the trial. 
12. As clinically indicated 
13. Until disease progression or until the start of a new anticancer therapy. CT will focus on the chest, abdomen, and pelvis. 
14. Assessments obtained prior the ICF signature as a part or standard of care/routine practice can be used for screening and trial purposes, provided the timelines for screening and cycle 1 day 1 are met 
15. Time to be recorded; starting from cycle 6, SOT102 and/or first-line SoC treatment can be administered on day 1 ±1 day 
16. Applicable only for AEs considered as having a suspected causal relationship to SOT102 per the investigator’s judgment 
17. Starting from cycle 2, safety laboratory samples can be collected 1 day early 
18. To be done also on day 14 and day 16 
19. Refer to section 8.6 
 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 25 of 131 
1.3.4 
Schedule of activities, Part C (SOT102 monotherapy, cohort expansion, CLDN18.2-positive tumors; pancreatic cancer second- or 
further-line) 
Visit 
Screening 
Day -1 
of 
each 
14-day 
cycle 
Day 1a 
Of each 14-day cycle 
Day 2 
of each 14-
day cycle 
Follow-up 
21 days 
before 
day 1 of 
cycle 1 
Within 21 
days before 
day 1 of 
cycle 1 
30 (+5) days 
after the last 
dose of SOT102 
Every 6 weeks (±2 weeks) until 
disease progression or start of 
new anticancer therapy 
Every 3 months (±2 weeks) during 
year 1 and then every 6 months 
(±2 weeks) until the end of the trial 
Informed consent1 
X 
 
 
 
 
 
 
 
Demography2 
 
X 
 
 
 
 
 
 
Cancer3 and medical history 
 
X 
 
 
 
 
 
 
Height 
 
X 
 
 
 
 
 
 
Pregnancy test 
 
X (blood)4 
 
Every other cycle (urine or blood)5 
 
X 
 
 
Physical examination 
 
X 
 
X5 
 
X 
 
 
Body weight and body surface area 
 
X 
 
X5 
 
X 
 
 
Vital signs6 
 
X 
 
X6 
 
X 
 
 
SaO2 
 
X 
 
X9 
 
X 
 
 
Clinical chemistry 
 
X4 
 
X5,20 
 
X 
 
 
Hematology 
 
X4 
 
X5,20 
 
X 
 
 
Coagulation (Quick) 
 
X4 
 
X5,20 
 
X 
 
 
Immunogenicity 
 
 
 
X5 
 
 
 
 
Urinalysis7 
 
X4 
 
X5,20 
 
X 
 
 
Creatinine clearance8 
 
X4 
 
X 
 
X 
 
 
HIV, hepatitis B 
 
 
 
X9 (HIV, HBV-positive patients 
only) 
 
 
 
 
ECG 
 
X 
 
X9 
 
X 
 
 
LVEF10 
 
X11 
 
X9 
 
X 
 
 
Esophagogastroduodenoscopy 
 
X12 
 
X9 
 
 
 
 
ECOG performance status 
 
X 
 
X 
 
X 
 
 
Tumor tissue or cytology sample (FFPE 
blocks) or unstained slides from archival 
biopsy or fresh biopsy 
X21 
 
 
 
 
 
 
 
Quality of life questionnaire – EORTC 
 
X 
 
X13 
 
X 
 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 26 of 131 
Visit 
Screening 
Day -1 
of 
each 
14-day 
cycle 
Day 1a 
Of each 14-day cycle 
Day 2 
of each 14-
day cycle 
Follow-up 
21 days 
before 
day 1 of 
cycle 1 
Within 21 
days before 
day 1 of 
cycle 1 
30 (+5) days 
after the last 
dose of SOT102 
Every 6 weeks (±2 weeks) until 
disease progression or start of 
new anticancer therapy 
Every 3 months (±2 weeks) during 
year 1 and then every 6 months 
(±2 weeks) until the end of the trial 
Quality of life questionnaire – EQ-5D-3L 
 
X 
 
X14 
 
 
X15 
Tumor assessment (CT, MRI)16 
 
X11 
 
Every 6 weeks (±2 weeks) after cycle 1 day 1 
Dexamethasone administration 
 
 
X 
X5 
X 
 
 
 
SOT102 administration17 
 
 
 
X 
 
 
 
 
AEs 
 
X 
 
X 
 
X 
  
 
Concomitant medication/non-drug 
therapies 
 
X 
 
X 
 
X 
 
X18 
Survival information 
 
 
 
 
 
 
 
X 
Blood for pharmacokinetic studies 
 
 
 
X19 
 
 
 
 
a. D1 is the day of SOT102 administration 
1. No trial-specific procedures are to be performed prior to ICF signature 
2. Demography includes the collection of information on age at screening, gender, race, and ethnicity 
3. Histology/cytology, initial diagnosis date, details about previous systemic and non-systemic treatment together with the associated disease response and date of last disease progression, and any prior mutations/genetic 
analysis 
4. To be done ≤ 7 days prior to enrollment 
5. Before SOT102 administration 
6. Vital signs include body temperature, blood pressure (systolic and diastolic, after ≥15 minutes of rest), and heart rate. To be measured before SOT102 administration, 15 (±5) minutes after the end of SOT102 infusion 
and 60 (±5) minutes after the end of SOT102 infusion. 
7. Urine analysis laboratory test other than dipstick must be performed. Entry limit at screening is grade 1 proteinuria (<1 g/24 hours). A test will be performed prior to each day 1 of each cycle and in case of ≥100 
mg/dL proteinuria, a 24-hour urine analysis will have to be performed (prior to the start of SOT102 treatment) to document 24-hour proteinuria levels. 
8. From serum creatinine, calculated by the Cockcroft-Gault formula; prior to SOT102 administration 
9. As clinically indicated 
10. Using either echocardiography or nuclear medicine methodology (MUGA scan). However, the method chosen needs to stay the same throughout the trial. 
11. Assessments obtained prior the ICF signature as a part or standard of care/routine practice can be used for screening and trial purposes, provided the timelines for screening and cycle 1 day 1 are met 
12. Up to 6 months before cycle 1 day 1 
13. Only in SOT102 cycle 1 and cycle 4 
14. Every other SOT102 treatment cycle (starting from cycle 1 day 1) 
15. Every 4 months (±2 weeks) until the end of trial (after year 1, every 6 months [±2 weeks] until the end of the trial) 
16. Until disease progression or until the start of a new anticancer therapy. CT will focus on the chest, abdomen, and pelvis. 
17. Time to be recorded; starting from cycle 2, SOT102 can be administered on day 1 ±1 day 
18. After 30 days after the last dose of SOT102, only further-line therapies are collected 
19. As specified in section 1.3.7 
20.  Starting from cycle 2, safety laboratory samples can be collected 1 day early 
21. Refer to section 8.6 
 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
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1.3.5 
Schedule of activities, Part D pancreatic (SOT102 combination with first-line SoC treatment, cohort expansion, CLDN18.2-
positive tumors; pancreatic cancer first-line) 
Visit 
Screening 
Day -1 
of each 
28-day 
SoC 
cycle 
Day 1a 
Of each 28-day 
SoC cycle 
Day 2 
of each 
28-day 
SoC 
cycle 
Day 8 
Of each 28-
day SoC 
cycle (±1 
day) 
Day 15a 
Of each 28-
day SoC cycle 
(±1 day) 
Day 21 
Of each 28-
day SoC 
cycle (±1 
day) 
Follow-up 
21 days 
before 
day 1 of 
cycle 1 
Within 21 
days before 
day 1 of 
cycle 1 
30 (+5) days 
after the last 
dose of 
SOT102 
Every 8 weeks (±2 
weeks) until 
disease progression 
or start of new 
anticancer therapy 
Every 3 months (±2 
weeks) during year 1 and 
then every 6 months 
(±2 weeks) until the end 
of the trial 
Informed consent1 
X 
 
 
 
 
 
 
 
 
 
 
Demography2 
 
X 
 
 
 
 
 
 
 
 
 
Cancer3 and medical history 
 
X 
 
 
 
 
 
 
 
 
 
Height 
 
X 
 
 
 
 
 
 
 
 
 
Pregnancy test 
 
X (blood)4  
 
Each cycle 
(urine or blood)5 
 
 
 
 
X 
 
 
Physical examination 
 
X 
 
X5 
 
 
X 
 
X 
 
 
Body weight and body surface area 
 
X 
 
X5 
 
 
X (weight 
only) 
 
X 
 
 
Vital signs6 
 
X 
 
X6 
 
X 
X6 
X 
X 
 
 
SaO2 
 
X 
 
X9 
 
 
 
 
X 
 
 
Clinical chemistry 
 
X4 
 
X5,20 
 
 
X5,20 
 
X 
 
 
Hematology 
 
X4 
 
X5,20 
 
X 
X5,20 
X 
X 
 
 
Coagulation (Quick) 
 
X4 
 
X5,20 
 
 
 
 
X 
 
 
Immunogenicity 
 
 
 
X5 
 
 
 
 
 
 
 
Urinalysis7 
 
X4 
 
X5,20 
 
 
X5,20 
 
X 
 
 
Creatinine clearance8 
 
X4 
 
X 
 
 
X 
 
X 
 
 
HIV, hepatitis B 
 
 
 
X9 (HIV, HBV-
positive patients 
only) 
 
 
 
 
 
 
 
ECG 
 
X 
 
X9 
 
 
X9 
 
X 
 
 
LVEF10 
 
X11 
 
X9 
 
 
 
 
X 
 
 
Esophagogastroduodenoscopy 
 
X12 
 
X9 
 
 
 
 
 
 
 
ECOG performance status 
 
X 
 
X 
 
X 
X 
X 
X 
 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 28 of 131 
Visit 
Screening 
Day -1 
of each 
28-day 
SoC 
cycle 
Day 1a 
Of each 28-day 
SoC cycle 
Day 2 
of each 
28-day 
SoC 
cycle 
Day 8 
Of each 28-
day SoC 
cycle (±1 
day) 
Day 15a 
Of each 28-
day SoC cycle 
(±1 day) 
Day 21 
Of each 28-
day SoC 
cycle (±1 
day) 
Follow-up 
21 days 
before 
day 1 of 
cycle 1 
Within 21 
days before 
day 1 of 
cycle 1 
30 (+5) days 
after the last 
dose of 
SOT102 
Every 8 weeks (±2 
weeks) until 
disease progression 
or start of new 
anticancer therapy 
Every 3 months (±2 
weeks) during year 1 and 
then every 6 months 
(±2 weeks) until the end 
of the trial 
Tumor tissue or cytology sample (FFPE 
blocks) or unstained slides from archival 
biopsy or fresh biopsy 
X22 
 
 
 
 
 
 
 
 
 
 
Quality of life questionnaire – EORTC 
 
X 
 
X13 
 
 
 
 
X 
 
 
Quality of life questionnaire – EQ-5D-3L 
 
X 
 
X14 
 
 
 
 
 
X15 
Tumor assessment (CT, MRI)16 
 
X11 
 
Every 8 weeks (±2 weeks) after cycle 1 day 1 
Dexamethasone administration 
 
 
X 
X5 
X 
 
X21 
 
 
 
 
SOT102 administration17 
 
 
 
X 
 
 
X 
 
 
 
 
Nab-paclitaxel/gemcitabine administration17 
 
 
 
X 
 
X 
X 
 
 
 
 
AEs 
 
X 
 
X 
 
X 
X 
X 
X 
 
 
Concomitant medication/non-drug therapies 
 
X 
 
X 
 
X 
X 
X 
X 
 
X18 
Survival information 
 
 
 
 
 
 
 
 
 
 
X 
Blood for pharmacokinetic studies 
 
 
 
X19 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 29 of 131 
a. D1 and D15 are the days of SOT102 administration 
1. No trial-specific procedures are to be performed prior to ICF signature 
2. Demography includes the collection of information on age at screening, gender, race, and ethnicity 
3. Histology/cytology, initial diagnosis date, details about previous systemic and non-systemic treatment together with the associated disease response and date of last disease progression, and any prior mutations/genetic 
analysis 
4. To be done ≤ 7 days prior to enrollment 
5. Before SOT102 administration 
6. Vital signs include body temperature, blood pressure (systolic and diastolic, after ≥15 minutes of rest), and heart rate. To be measured before SOT102 administration, 15 (±5) minutes after the end of SOT102 infusion 
and 60 (±5) minutes after the end of SOT102 infusion. 
7. Urine analysis laboratory test other than dipstick must be performed. Entry limit at screening is grade 1 proteinuria (<1 g/24 hours). A test will be performed prior to each day 1 of each cycle and in case of ≥100 
mg/dL proteinuria, a 24-hour urine analysis will have to be performed (prior to the start of SOT102 treatment) to document 24-hour proteinuria levels. 
8. From serum creatinine, calculated by the Cockcroft-Gault formula; prior to SOT102 administration 
9. As clinically indicated 
10. Using either echocardiography or nuclear medicine methodology (MUGA scan). However, the method chosen needs to stay the same throughout the trial. 
11. Assessments obtained prior the ICF signature as a part or standard of care/routine practice can be used for screening and trial purposes, provided the timelines for screening and cycle 1 day 1 are met 
12. Up to 6 months before cycle 1 day 1 
13. Only in SOT102 cycle 1 and cycle 4 
14. Every other SOT102 treatment cycle (starting from cycle 1 day 1) 
15. Every 4 months (±2 weeks) until the end of trial (after year 1, every 6 months [±2 weeks] until the end of the trial) 
16. Until disease progression or until the start of a new anticancer therapy. CT will focus on the chest, abdomen, and pelvis. 
17. Time to be recorded; starting from cycle 2, SOT102 can be administered on day 1 ±1 day 
18. After 30 days after the last dose of SOT102, only further-line therapies are collected 
19. As specified in section 1.3.7 
20. Starting from cycle 2, safety laboratory samples can be collected 1 day early 
21. To be done also on day 14 and day 16 
22. Refer to section 8.6 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
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1.3.6 
PK and ADA sampling (SOT102), Part A and Part B 
All attempts should be made to collect the samples on time. Missed sample collections are considered 
Protocol deviations. The numbers in parentheses are the expected blood/urine sampling volumes in mL. 
Patients may be hospitalized for 24 hours in cycles 1, 3, and 5 for collection of PK samples. 
An additional PK sample must be collected at the occurrence of any grade ≥3 AE or an intolerable 
persistent grade 2 AE after the DLT evaluation period in Part A and Part B and at the time (pre-dose) 
when these events have resolved and SOT102 treatment is resumed. In particular, a PK sample must be 
collected in the event of a grade 4 AE leading to permanent discontinuation of SOT102. 
Purpose 
Cycle 
Day 
of 
cycle 
Time point  
(pre-dose or time after the end of SOT102 infusion) 
SOT102 PK 
Part A 
Part B 
PK analytes 
PK parameters 
- blood 
1 
1 
Cycle 1 day 1 pre-dose 
X (5) 
X (5) 
1 
1 
Within 15 minutes after end of SOT102 infusion 
X (5) 
X (5) 
1 
1 
3 hours (±15 minutes) 
X (5) 
X (5) 
1 
1 
6 hours (±15 minutes) 
X (5) 
X (5) 
1 
2 
24 hours (±2 hours) 
X (5) 
X (5) 
1 
4 
72 hours (±2 hours) 
X (5) 
X (5) 
1 
5 
Day 5 
X (5) 
X (5) 
1 
8 
Day 8 
X (5) 
X (5) 
1 
11 
Day 11 
X (5) 
X (5) 
1 
15 
Day 15 (in case cycle 2 day 1 is postponed) 
X (5) 
X (5) 
2 
1 
Cycle 2 day 1 pre-dose (can be replaced by sample 
collected on day 15 unless cycle 2 day 1 is postponed) 
X (5) 
X (5) 
2 
1 
Within 15 minutes after end of SOT102 infusion 
X (5) 
X (5) 
3 
1 
Cycle 3 day 1 pre-dose 
X (5) 
X (5) 
3 
1 
Within 15 minutes after end of SOT102 infusion 
X (5) 
X (5) 
3 
1 
3 hours (±15 minutes) 
X (5) 
X (5) 
3 
1 
6 hours (±15 minutes) 
X (5) 
X (5) 
3 
2 
24 hours (±2 hours) 
X (5) 
X (5) 
3 
4 
72 hours (±2 hours) 
X (5) 
X (5) 
3 
5 
Day 5 
X (5) 
X (5) 
3 
8 
Day 8 
X (5) 
X (5) 
3 
11 
Day 11 
X (5) 
X (5) 
3 
15 
Day 15 (in case cycle 4 day 1 is postponed) 
X (5) 
X (5) 
4 
1 
Cycle 4 day 1 pre-dose (can be replaced by sample 
collected on day 15) 
X (5) 
X (5) 
4 
1 
Within 15 minutes after end of SOT102 infusion 
X (5) 
X (5) 
5 
1 
Cycle 5 day 1 pre-dose 
X (5) 
X (5) 
5 
1 
Within 15 minutes after end of SOT102 infusion 
X (5) 
X (5) 
5 
1 
3 hours (±15 minutes) 
X (5) 
X (5) 
5 
1 
6 hours (±15 minutes) 
X (5) 
X (5) 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 31 of 131 
Purpose 
Cycle 
Day 
of 
cycle 
Time point  
(pre-dose or time after the end of SOT102 infusion) 
SOT102 PK 
Part A 
Part B 
5 
2 
24 hours (±2 hours) 
X (5) 
X (5) 
5 
4 
72 hours (±2 hours) 
X (5) 
X (5) 
5 
5 
Day 5 
X (5) 
X (5) 
5 
8 
Day 8 
X (5) 
X (5) 
5 
11 
Day 11 
X (5) 
X (5) 
5 
15 
Day 15 (can be collected prior to cycle 6 day 1 if 
timing matches the desired schedule) 
X (5) 
X (5) 
 
Additional PK sample to be collected at the time of occurrence of grade ≥3 
AE, at the time SOT102 treatment resumes, and at the time of occurrence of 
grade 4 AE 
X (5) 
X (5) 
 
Additional PK sample to be collected in conjunction with ADA sample at the 
time of disease progression (clinical or radiological per RECIST 1.1) ** 
X (5) 
X (5) 
PK 
concentrations 
- urine 
1 
1 
Up to 24-hour collection (starting cycle 1 day 1 pre-
dose)* 
X  
(approx. 50) 
X  
(approx. 50) 
ADA 
assessment** 
1 
1 
Cycle 1 day 1 pre-dose 
X (5) 
X (5) 
1 
15 
Day 15 
X (5) 
X (5) 
2 
1 
Cycle 2 day 1 pre-dose (can be collected together with 
day 15 sample unless cycle 2 day 1 is postponed) 
X (5) 
X (5) 
3 
1 
Cycle 3 day 1 pre-dose 
X (5) 
X (5) 
3 
15 
Day 15 (in case cycle 2 day 1 is postponed) 
X (5) 
X (5) 
4 
1 
Cycle 4 day 1 pre-dose (can be replaced by sample 
collected on day 15) 
X (5) 
X (5) 
- 
- 
Every 2 months in subsequent cycles 
X (5) 
X (5) 
- 
- 
30 days after the last dose of SOT102 
X (5) 
X (5) 
 
Additional ADA sample to be collected at the time of disease progression 
(clinical or radiological per RECIST 1.1) ** 
X (5) 
X (5) 
*Exact time points will be specified in the Laboratory Manual 
**This sample can be substituted by regular sampling, if performed within ±14 days of the disease progression. 
 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
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1.3.7 
PK and ADA sampling (SOT102), Part C and Part D 
All attempts should be made to collect the samples on time. Missed sample collections are considered 
Protocol deviations. The numbers in parentheses are the expected blood/urine sampling volumes in mL. 
In Part C and Part D, sparse PK sampling will be performed to allow for population PK modeling and 
exposure-response analysis in order to facilitate dose selection for further trials. The exact time points 
will be based on an analysis of PK parameters in parts A and B and will at least include the below time 
points. 
An additional PK sample must be collected at the occurrence of any grade ≥3 AE or an intolerable 
persistent grade 2 AE after the first cycle in Part C and Part D and at the time (pre-dose) when these 
events have resolved and SOT102 treatment is resumed. In particular, a PK sample must be collected 
in the event of a grade 4 AE leading to permanent discontinuation of SOT102. 
Purpose 
Day of 
each cycle 
Time point  
(pre-dose or time after the end of SOT102 
infusion) 
SOT102 PK 
Part C 
Part D 
PK analytes 
PK parameters - 
blood 
1 
Day 1 pre-dose 
X (5) 
X (5) 
1 
Within 15 minutes after end of SOT102 
infusion 
X (5) 
X (5) 
8 
Day 8 
X (5) 
X (5) 
 
Additional PK sample to be collected at the time of 
occurrence of grade ≥3 AE, at the time SOT102 treatment 
resumes, and at the time of occurrence of grade 4 AE 
X (5) 
X (5) 
 
Additional PK sample to be collected in conjunction with 
ADA sample at the time of disease progression (clinical or 
radiological per RECIST 1.1) ** 
X (5) 
X (5) 
ADA assessment* 
1 
Day 1 pre-dose 
X (5) 
X (5) 
1 
Within 15 minutes after end of SOT102 
infusion 
X (5) 
X (5) 
 
Additional ADA sample to be collected at the time of 
disease progression (clinical or radiological per RECIST 
1.1) ** 
X (5) 
X (5) 
*Exact time points will be specified in the Laboratory Manual 
**This sample can be substituted by regular sampling, if performed within ±14 days of the progression. 
 
 

 
 
 
 
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2 INTRODUCTION 
2.1 Trial rationale 
CLDN18.2, splice variant 2 of claudin 18, represents a potentially attractive tumor-associated 
antigen. In order to make use of the exclusive expression of CLDN18.2 in gastric and 
pancreatic cells and the fact that transient gastrointestinal toxicity is a manageable adverse 
event (AE), SOTIO developed SOT102, an antibody-drug conjugate (ADC) targeting 
CLDN18.2 with the anthracycline 
 as cytotoxic moiety for the treatment of 
CLDN18.2-positive pancreatic adenocarcinoma. SOT102 was potent in killing of CLDN18.2-
positive tumor cells in vitro and inhibited tumor growth in vivo. These findings offer preclinical 
proof-of-principle that SOT102 is highly specific and potent and warrant exploration in a 
clinical trial. 
The original intention of the trial was to investigate its objectives in two indications - 
gastric/GEJ cancer and pancreatic cancer. Following a reassessment of the benefit/risk ratio, it 
was decided by the sponsor to halt the clinical development in gastric/GEJ cancer for the time 
being and proceed only with pancreatic cancer. For more details see the IB. 
2.2 Background 
Despite recent advances in the treatment of many types of cancer, the prognosis of gastric and 
pancreatic adenocarcinomas remains disappointing. Each year, gastric cancer is diagnosed in 
over one million people worldwide.1 The disease is only rarely cured2,3 and has a high case 
fatality rate. 
With approximately 500,000 new cases each year worldwide, pancreatic cancer is not as 
prevalent as gastric cancer, but it is one of the most lethal tumors.1 Pancreatic surgery of 
resectable disease and chemotherapy with a combination of folinic acid (leucovorin),  
5-fluorouracil (5-FU), irinotecan, and oxaliplatin; gemcitabine monotherapy; gemcitabine and 
erlotinib; gemcitabine and capecitabine, or gemcitabine plus albumin-bound paclitaxel with or 
without chemoradiation are the current treatments for the different stages of pancreatic cancer, 
but their outcomes are dismal. About 92% of patients with pancreatic cancer die within 5 years 
of their diagnosis.4 
Limited treatment options are available for patients with metastatic pancreatic cancer, where 
the existing second-line therapy has only a modest treatment effect in such patients.5 Therefore, 
there is a high unmet medical need for therapeutic options in patients with pancreatic cancer 
who are eligible for treatment with advanced lines. 
The current standard of care (SoC) for first-line treatment of advanced pancreatic cancer is 
dependent on disease stage and the patient’s performance status. Gemcitabine as monotherapy 
or in combination with various other agents is often the first choice for treatment of this disease. 
Paclitaxel protein-bound (nab-paclitaxel)/gemcitabine was recently approved for first-line 
treatment of metastatic pancreatic cancer. Nab-paclitaxel plus gemcitabine led to a significant 
improvement in survival.6 Therefore, the nab-paclitaxel plus gemcitabine regimen has been 
selected as an appropriate choice for first-line treatment of advanced pancreatic cancer, which 
will be explored in Part B and in Part D. 
With treatment options in the first-line setting in gastric/GEJ and pancreatic cancers well-
established, the development of SOT102 in this setting required a combination therapy. 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 34 of 131 
Modified oxaliplatin + leucovorin + 5-FU containing chemotherapy regimen (mFOLOFOX6) 
regimen has been shown to demonstrate comparable efficacy with another standard of care 
(SoC) treatment in patients with advanced gastric/GEJ cancer, while showing more favorable 
safety profile with less non-hematologic toxicities.7 mFOLFOX6 treatment is widely accepted 
and also recommended by the European Society for Medical Oncology guidelines.2 Recently, 
nivolumab in combination with mFOLFOX6 has been approved in the US and in the EU8,9; 
therefore, this combination has been selected as an appropriate choice for first-line treatment 
of locally advanced inoperable and metastatic gastric or GEJ cancer, which is explored in Part 
B. 
The poor prognosis of these cancer types warrants exploration of additional treatment options. 
One such option is that of targeted therapies, including ADCs. The covalent linking of a 
cytotoxic “payload”, such as DNA-damaging agents or tubulin polymerization inhibitors, to an 
antibody to form an ADC provides a mechanism for selective delivery of the cytotoxic agent 
to cancer cells via the specific binding of the antibody to cancer-selective cell surface 
molecules. ADC strategies do not only enhance the therapeutic window of potent cytotoxic 
drugs, but also minimize chemotherapy-associated side effects. Antibodies, payloads, and 
cleavable or non-cleavable linkers can be combined so that the resulting ADCs have various 
characteristics.10 
The US Food and Drug Administration’s approval of brentuximab vedotin (Adcetris®) in 
201111 has validated the ADC concept in cancer treatment and stimulated intensive research 
which led to regulatory approvals of ADCs now used in clinical practice.12-20 
The claudin multigene family encodes proteins with four membrane-spanning domains that are 
crucial structural and functional components of tight junctions. In mammals, there are at least 
27 claudin members identified and they exhibit complex tissue-specific patterns of 
expression.21 CLDN18.2 is highly expressed in the normal stomach, is strictly confined to 
short-lived gastric epithelial cells, and is absent from the vast majority of healthy tissues. 
Furthermore, CLDN18.2 is expressed in a significant proportion of primary gastric cancers (up 
to 96%), GEJ cancers (up to 78%), and ductal pancreatic cancers (up to 80%) and their 
metastases.22 
The strong antitumor activity of SOT102 was demonstrated in vivo in several relevant mouse 
models, engrafted with patient-derived gastric, pancreatic, colon, lung, and liver tumors. 
Importantly, SOT102 was active in vivo against tumors expressing CLDN18.2 at high, 
intermediate, and low levels. The beneficial effect of SOT102 treatment supports the clinical 
evaluation of this treatment approach. For more detailed information please see the 
Investigator’s Brochure (IB). 
2.3 Benefit/risk assessment 
Based on preclinical toxicology and efficacy studies, it is assumed that the clinical benefits of 
SOT102 will outweigh the potential risks. More detailed information about the known and 
anticipated benefits and risks and potential AEs that could be associated with the administration 
of SOT102 may be found in the IB. The original intention of the trial was to investigate its 
objectives in two indications - gastric/GEJ cancer and pancreatic cancer. Following a 
reassessment of the benefit/risk ratio, it was decided by the sponsor to halt the clinical 
development in gastric/GEJ cancer for the time being and proceed only with pancreatic cancer. 
For more details see the IB. 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 35 of 131 
3 OBJECTIVES AND ENDPOINTS 
Table 3.1: Part A (SOT102, monotherapy, dose escalation) 
Objective 
Endpoint 
Primary 
• To determine the maximum tolerated 
dose (MTD) and recommended phase 2 
dose (RP2D) of SOT102 given as 
monotherapy. 
• MTD is defined as the highest dose level 
tested below the dose level associated 
with ≥33% of dose-limiting toxicity 
(DLT)-evaluable patients experiencing 
DLT. The RP2D will be selected based on 
integrated evaluation of the totality of 
clinical and preclinical data, for all dose 
levels tested. 
Secondary 
• To assess the safety and tolerability of 
SOT102 in monotherapy. 
• The occurrence of DLTs, occurrence of 
treatment-emergent 
AEs 
(TEAEs), 
SOT102-related 
AEs, 
serious 
AEs 
(SAEs), AEs leading to premature 
discontinuation of SOT102, deaths, or 
clinical laboratory test abnormalities 
• To characterize the pharmacokinetics 
(PK) of total SOT102, conjugated 
SOT102, 
 
 
 
 
 
• PK of total SOT102, conjugated SOT102, 
 
 
 
 
• To explore evidence of SOT102 activity 
in monotherapy in individual patients. 
• Anecdotal tumor response per Response 
Evaluation Criteria in Solid Tumors 
(RECIST) 1.123 by type and CLDN18.2 
expression 
• To explore whether patients develop any 
antibodies against SOT102. 
• The number of patients with detected 
antibodies against any part of SOT102 
Table 3.2: Part B (SOT102 combined with first-line SoC treatment, dose escalation) 
Objective 
Endpoint 
Primary 
• To determine the MTD and RP2D of 
SOT102 in combination with first-line 
SoC treatment. 
• MTD is defined as the highest dose level 
tested below the dose level associated 
with ≥33% of DLT-evaluable patients 
experiencing DLT. The RP2D will be 
selected based on integrated evaluation of 
the totality of clinical and preclinical data, 
for all dose levels tested. 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 36 of 131 
Objective 
Endpoint 
Secondary 
• To assess the safety and tolerability of 
SOT102 in combination with first-line 
SoC treatment. 
• The occurrence of DLTs, occurrence of 
TEAEs, SOT102-related AEs, SAEs, AEs 
leading to premature discontinuation of 
SOT102, deaths, or clinical laboratory 
test abnormalities 
• To characterize the PK of total SOT102, 
conjugated SOT102, 
 
 
 
 
• PK of total SOT102, conjugated SOT102, 
 
 
 
 
• To explore evidence of SOT102 activity 
in combination with first-line SoC 
treatment in individual patients. 
• Anecdotal tumor response per RECIST 
1.1 by type and CLDN18.2 expression 
• To explore whether patients develop any 
antibodies against SOT102. 
• The number of patients with detected 
antibodies against any part of SOT102 
Table 3.3: Part C (SOT102 monotherapy, cohort expansion) 
Objective 
Endpoint 
Primary 
• To assess the efficacy of SOT102 in 
monotherapy. 
• Objective response rate (ORR) 
Secondary 
• To evaluate additional measures of 
efficacy of SOT102 in monotherapy. 
• Duration of response (DoR), progression-
free survival (PFS) and clinical benefit 
rate per RECIST 1.1, overall survival 
(OS) 
• To assess the safety and tolerability of 
SOT102 in monotherapy. 
• The occurrence of TEAEs, SOT102-
related AEs, SAEs, AEs leading to 
premature discontinuation of SOT102, 
deaths, 
or 
clinical 
laboratory 
test 
abnormalities 
• To assess quality of life (QoL) after 
treatment with SOT102 in monotherapy. 
• Assessment of global and disease-specific 
QoL by patient-reported questionnaires 
EORTC QLQ-C30 and EORTC QLQ-
PAN26 for patients with pancreatic 
cancer 
• To characterize the PK of total SOT102, 
conjugated SOT102, 
 
 
 
 
• PK of total SOT102, conjugated SOT102, 
 
 
 
 
• To explore whether patients develop any 
antibodies against SOT102. 
• The number of patients with detected 
antibodies against any part of SOT102 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
Page 37 of 131 
Objective 
Endpoint 
Exploratory 
• To assess the relationship between the 
intensity of CLDN18.2 expression and 
clinical outcome 
• Relationship between the intensity of 
CLDN18.2 
expression 
and 
clinical 
outcome 
Table 3.4: Part D (SOT102 combined with first-line SoC treatment, cohort expansion) 
Objective 
Endpoint 
Primary 
• To assess the efficacy of SOT102 in 
combination 
with 
first-line 
SoC 
treatment. 
• ORR 
Secondary 
• To evaluate additional measures of 
efficacy of SOT102 in combination with 
first-line SoC treatment. 
• DoR and PFS per RECIST 1.1, OS 
• To assess the safety and tolerability of 
SOT102 in combination with first-line 
SoC treatment. 
• The occurrence of TEAEs, SOT102-
related AEs, SAEs, AEs leading to 
premature discontinuation of SOT102, 
deaths, 
or 
clinical 
laboratory 
test 
abnormalities 
• To assess QoL after treatment with 
SOT102 in combination with SoC 
treatment. 
• Assessment of global and disease-specific 
QoL by patient-reported questionnaires 
EORTC QLQ-C30 and EORTC QLQ-
PAN26 for patients with pancreatic 
cancer 
• To characterize the PK of total SOT102, 
conjugated SOT102, 
 
 
 
 
• PK of total SOT102, conjugated SOT102, 
 
 
 
 
• To explore whether patients develop any 
antibodies against SOT102 
• The number of patients with detected 
antibodies against any part of SOT102 
Exploratory 
• To assess the relationship between the 
intensity of CLDN18.2 expression and 
clinical outcome 
• Relationship between the intensity of 
CLDN18.2 
expression 
and 
clinical 
outcome 
 

 
 
 
 
SN201_Protocol_Amendment 5_Final_04Jun2024 
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4 TRIAL DESIGN 
4.1 Overall design 
This trial will assess the MTD and RP2D of SOT102 administered as monotherapy (Part A) 
and in combination with first-line SoC treatment (nab-paclitaxel/gemcitabine for pancreatic 
cancer, mFOLFOX6 with nivolumab for gastric/GEJ cancer; Part B) and efficacy of SOT102 
administered as monotherapy (Part C) and in combination with first-line SoC treatment (Part 
D) in patients with inoperable or metastatic pancreatic adenocarcinoma whose tumor expresses 
CLDN18.2 and in ongoing patients with advanced inoperable or metastatic gastric/GEJ 
adenocarcinoma, who were enrolled in the trial prior to this Protocol Amendment, and are 
allowed to continue SoC therapy without SOT102 until criteria for SoC therapy discontinuation 
are met. 
CLDN18.2 positivity is determined by immunohistochemistry (IHC) assay. Pancreatic tumor 
must have medium to high (2+3+) CLDN18.2 membranous staining on ≥75% of tumor cells 
by IHC. 
The trial has the following parts: 
• Part A: Dose escalation, first in human, single-agent phase 1 trial of SOT102 in 
advanced/metastatic gastric/GEJ or CLDN18.2-positive pancreatic cancer patients with 
unmet medical need. Gastric/GEJ cohort is currently halted, and no new patients will be 
enrolled (for details see the IB). 
• Part B gastric cohort: Phase 1b dose escalation combination trial of SOT102 in 
combination with mFOLFOX6 and nivolumab as SoC regimen for first-line treatment of 
patients with advanced/metastatic gastric/GEJ cancer which that started once monotherapy 
SOT102 dose level 3 in Part A was successfully completed and was safe; the starting dose 
of Part B was dose level 1 of Part A. This part is currently halted, and no new patients will 
be enrolled (for details see the IB). 
Part B pancreatic cohort: Phase 1b dose escalation combination trial of SOT102 in 
combination with nab-paclitaxel/gemcitabine as SoC regimen for first-line treatment of 
CLDN18.2-positive patients with advanced/metastatic pancreatic cancer which will start 
once monotherapy SOT102 dose level 3 in Part A is successfully completed and is safe; 
the starting dose of Part B will be dose level 1 of Part A 
Once an RP2D in the respective phase 1 evaluation (Part A and Part B) has been identified, 
expansion cohorts for pancreatic cancer (Part C and Part D) are planned: 
• Part C: Single-agent SOT102 expansion at RP2D identified in Part A in CLDN18.2-
positive pancreatic cancer after one or more prior systemic therapies (second+ line) for 
locally advanced or metastatic disease 
Part D: SOT102 in combination with nab-paclitaxel/gemcitabine for first-line treatment 
expansion at RP2D identified in Part B in CLDN18.2-positive pancreatic cancer 
4.1.1 
Dose escalation plan (Part A and Part B) 
The DLT evaluation period is 28 days counted from day 1 of cycle 1 of SOT102. 
A patient evaluable for DLT will be a patient who has received 2 doses of SOT102 per schedule 
(day 1 of cycle 1 and day 1 of cycle 2) with the maximum postponement of cycle 2 by 1 day 

 
 
 
 
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(as agreed by the sponsor) and who completed the evaluation period of 28 days. Patients who 
do not fulfill these criteria for any reason other than DLT will be replaced. 
In addition to above-mentioned requirements for SOT102 monotherapy, a DLT-evaluable 
patient in Part B must also meet the following requirements regarding SoC treatment: 
• Pancreatic patient who has received three doses of SoC (days 1, 8, and 15 of cycle 1) 
After completion of the DLT evaluation period with the adequate number of evaluable patients, 
all data as specified in a Dose Escalation Committee (DEC) Charter will be reviewed during a 
Dose Escalation Meeting (DEM) by the DEC. The decision as to whether an AE should be 
considered as DLT and/or whether a dose level is to be considered intolerable will be made by 
the DEC. The DEC membership is defined in the DEC Charter. 
In the event of a confirmed non-tolerable dose at any dose level, the sponsor will inform all 
sites immediately. Patients who will not be DLT-evaluable will be replaced. Replaced patients 
can continue with trial treatment if there is clinical benefit and upon consent with the sponsor. 
The dose escalation plan will follow a 3+3 design as described by Hanauske and von Hoff24 
and will include a safety observation period. 
If one of the first three patients of a dose level experiences DLT, three more patients will be 
treated at the same dose level. 
The dose escalation continues until DLTs are observed in ≥2 DLT-evaluable patients at a given 
dose level. The MTD will be declared as the highest dose level tested below that particular 
dose level. At least 6 DLT-evaluable patients will be included to assess the RP2D before the 
respective expansion parts C and D are initiated. 
Staggered enrollment of patients: 
For each dose level, the first patient will be observed for safety starting from day 1 of cycle 1 
(see section 8.2.3.1). If there are no safety concerns after 28 days, the responsible investigator 
will notify the sponsor’s medical monitor and the second and third patients will be allowed to 
be dosed according to the following: if the first patient experiences ≤ grade 1 toxicity, the two 
subsequent patients can be dosed. If the first patient experiences ≥ grade 2 toxicity, each of the 
two subsequent patients will have an observational period of one week before the next patient 
can be dosed. 
For more details see Figure 4.1.

 
 
 
 
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Figure 4.1: Dose escalation flowchart for Part A and Part B (staggered dosing and 3+3 design) 
 
 
 
 
 
 
 
 
 
 
 
* The DEC will review, discuss, and decide on the next steps of the trial. 
** In the case of 1 DLT only, additional patients may be enrolled without a formal DEC meeting (notification to DEC about the additional enrollment is sufficient) 
DEC, Dose Escalation Committee; DLT, dose-limiting toxicity 
 
≥2 DLTs in 
evaluable 
patients 
First patient at 
each dose 
level 
28 days safety 
observation 
period 
≤ grade 1 
toxicity in first 
patient 
 ≥ grade 2 
toxicity in first 
patient 
DLT assessment  
at the end of the 
DLT evaluation 
period (28 days) 
in all 3 patients 
Dose second and third 
patients at the same dose 
level, no waiting period 
Enroll additional  
3 patients (no waiting 
period) to  
a total of 6 evaluable 
patients or 2 DLTs, 
whichever occurs earlier 
≥2 DLTs in 
evaluable 
patients 
**1 DLT in 
evaluable 
patients 
0 DLT  
in 3 patients 
1 DLT in 6 
patients 
STOP dose escalation 
*Review 
by DEC 
Next higher 
dose level 
Dose second and third 
patients at the same dose 
level, 1 week waiting 
period 
*Review 
by DEC 
DLT assessment 
at the end of the 
DLT evaluation 
period in all 6 
patients OR 2 
DLTs observed 
(whichever 
occurs earlier)  

 
 
 
 
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4.1.1.1 Dose-limiting toxicities definitions 
DLTs will be AEs as specified below and graded according to National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. The AEs listed 
below will be considered DLTs unless clearly not related to SOT102 (e.g., events clearly due 
to cancer disease, other comorbid illness, or unequivocally related to concomitant medications 
or SoC treatment in Part B). The DLT evaluation period is 28 days counted from day 1 of cycle 
1. Every DLT in the trial will be discussed between the trial investigators and sponsor and 
every effort will be made to ensure all clinical assessments are carried out and documented 
appropriately. 
AEs that are considered DLTs: 
• All grade 5 events not clearly related to disease progression, or any other causes will be 
considered DLTs. 
• Any grade 3 or higher non-hematologic toxicity regardless of duration will be considered 
a DLT. The exceptions below are NOT considered DLTs: 
o Grade 3 nausea, vomiting, or diarrhea that can be controlled within 72 hours 
o Grade 3 fatigue less than 5 days 
o Grade 3 or higher correctable electrolyte abnormalities that last less than 72 hours and 
not associated with clinical complications 
o Grade 3 or higher amylase or lipase not associated with symptoms, or clinical 
manifestations, or radiological evidence of pancreatitis 
• Grade 2 or higher serum creatinine elevation 
• Hy’s law cases will be considered DLTs (see section 10.2) 
• Hematologic DLTs will include the following: 
o Grade 4 neutropenia lasting more than 7 days 
o Febrile neutropenia 
o Grade 3 thrombocytopenia with bleeding 
o Grade 4 thrombocytopenia 
• Any grade 2 pneumonitis that does not resolve to grade 1 within 3 days of the initiation of 
maximal supportive care 
• Recurrent grade 2 pneumonitis 
• Grade 2 or higher proteinuria 
Other clinically significant toxicities, including a single event or multiple occurrences of the 
same event, may be considered as DLTs. 
AEs occurring after the DLT evaluation period may be considered DLT-like events upon DEC 
discussion. If required, a DEM will be set up to assess these events. 
Patients who develop toxicities qualified as DLTs will be discontinued from therapy, unless 
the investigator determines that the patient has a clear and demonstrable clinical benefit from 
treatment at the same time. 

 
 
 
 
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4.1.1.2 Maximum tolerated dose and selection of the recommended phase 2 dose 
If the MTD is reached, the RP2D will be defined based on all available clinical and preclinical 
information. At least 6 DLT-evaluable patients will be included to assess the RP2D before the 
respective expansion parts C and D are initiated. 
4.1.1.3 Dose escalation meetings 
A DEM will regularly take place after the last patient of the dose level has completed the DLT 
evaluation period (28 days counted from day 1 of cycle 1) with or without DLTs and is 
evaluable for DLT assessment. In case of unforeseen severe toxicities, a DEM can be called at 
any time. 
The decision as to whether AEs should be considered as DLTs and/or whether a dose level is 
to be considered intolerable will be made by the DEC. In the event of a confirmed non-tolerable 
dose at any dose level, the sponsor will inform all sites immediately. 
At every DEM, the totality of clinical and preclinical data will be reviewed by the DEC and 
will be taken into consideration by the DEM panel. 
4.1.1.4 Safety monitoring 
4.1.1.4.1 Part A 
Patients will be monitored for all AEs which might be associated with SOT102 administration 
for 30 days after the last dose of SOT102 and for AEs considered as having a suspected causal 
relationship to SOT102 per the investigator’s judgment until disease progression or start of 
new anticancer therapy. These AEs will be monitored every 6 weeks (±2 weeks) during the 
follow-up period (see section 4.1.2.4). Any late toxicities will be considered in the 
determination of the MTD/RP2D and dose schedules for Part A. 
4.1.1.4.2 Part B 
Patients will be monitored at the same visits and with assessments as specified in Part A (for 
30 days after the last dose of SOT102 and every 6 weeks [±2 weeks] until disease progression 
or start of new anticancer therapy) during the combination treatment with SOT102 (see section 
4.1.3.4). Any late toxicities will be considered in the determination of the MTD/RP2D and dose 
schedules for Part B. 
The following immune-related reactions were reported in patients treated with nivolumab: 
immune-mediated pneumonitis, immune-mediated colitis, immune-mediated hepatitis and 
hepatotoxicity, immune-mediated endocrinopathies, immune-mediated nephritis with renal 
dysfunction, immune-mediated dermatologic adverse reactions, and other immune-mediated 
adverse reactions (including myocarditis, pericarditis, vasculitis, uveitis, iritis, and other ocular 
inflammatory toxicities, pancreatitis, myositis/polymyositis, rhabdomyolysis, and associated 
sequelae including renal failure, arthritis, polymyalgia rheumatic, hypoparathyroidism, 
hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic 
inflammatory 
response 
syndrome, 
histiocytic 
necrotizing 
lymphadenitis 
[Kikuchi 
lymphadenitis], sarcoidosis, immune thrombocytopenic purpura, and solid organ transplant 
rejection).9,25 All immune-related reactions should be managed according to local standards. 
No 
immune-related 
reactions 
were 
reported 
in 
patients 
treated 
with 
nab-
paclitaxel/gemcitabine.26,27 

 
 
 
 
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The following immune-related reactions were reported in patients treated with mFOLFOX6: 
allergic reactions/allergy (including anaphylactoid/anaphylactic reactions and urticaria); 
hypersensitivity reactions; bronchospasm, immunosuppression with an increased risk of 
infection.28-30 All immune-related reactions should be managed according to local standards. 
4.1.1.5 Patient recruitment management 
The trial will recruit patients to all ongoing trial parts in parallel. 
The sponsor will allocate slots for the patients to be recruited to the dose-escalation trial parts. 
Potentially eligible patients will be communicated to the sponsor (on an ad-hoc basis and/or at 
regular meetings) and will be assessed for enrollment with the aim of recruiting patients to a 
specific dose level as quickly as the rules set out in the dose escalation flowchart allow  
(Figure 4.1). Available slots will be distributed by the sponsor upon discussion with specific 
sites to ensure appropriate distribution of patients (e.g., regionally). Back-up slots for screen 
failure patients or potential failure to manage the DLT evaluation period will also be secured 
in advance, if possible. 
4.1.1.6 Communication plan 
Trial investigators will inform the sponsor’s medical monitor via an immediate phone call in 
case of an urgent safety signal, including but not limited to DLTs, life-threatening immune 
reactions, unexpected event likely to seriously affect the benefit-risk balance of SOT102, and 
serious safety-related Protocol deviations. The sponsor’s medical monitor will ensure all sites 
are informed immediately, and any preventive measure is put in place, including stopping 
recruitment temporarily, if required. In case of a DLT, this immediate phone call will be 
followed by submission of required information within 24 hours via an electronic case report 
form (eCRF) or via email. The sponsor’s medical monitor will immediately inform all sites and 
a DEM may be arranged. The DEM will assess whether the type and extent of toxicities 
observed warrants informing all patients enrolled in the trial and will work with investigators 
to share findings as appropriate. 
Regular trial teleconferences will be held between trial investigators (or designated 
sub-investigators) and the sponsor’s medical monitor. In addition to a review of potential 
patients for recruitment and updates on the status of ongoing patients, any emerging safety 
issues will be discussed. At these regular teleconferences, the trial investigator or designated 
sub-investigator will also inform the sponsor’s medical monitor of any important toxicities or 
DLT-like events occurring in the subsequent cycles, i.e., beyond the DLT evaluation period. 
This will allow appropriate actions to be taken. 
Ad-hoc meetings with the trial investigators or designees may also be arranged to discuss any 
safety concerns during the trial. 
4.1.2 
Part A (SOT102 monotherapy, dose escalation) 
In Part A, patients with CLDN18.2-positive pancreatic adenocarcinoma will be treated with 
escalating doses of SOT102 given once every 14 days via the intravenous (IV) route over 45 
(±15) minutes. If medically indicated, an extension of the infusion time up to 120 minutes is 
allowed. In this case, the sponsor must be informed. However, a total duration of 120 minutes 
should not be exceeded. 
A starting dose of 0.032 mg/kg was selected in Part A of this trial. If only grade ≤1 therapy-
related toxicities are observed during cycle 1 in the first three patients at a given dose level, the 

 
 
 
 
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dose will be increased by 100% for the next dose level. If grade ≥2 therapy-related toxicities 
are observed during cycle 1 in any patient at a particular dose level, the dose will be increased 
by de-escalating dose increases following a modified Fibonacci scheme. These adjustments of 
the planned dose levels and dose increments will be considered by the DEC. 
SOT102 monotherapy dose escalation will continue until DLTs are observed in ≥2 DLT-
evaluable patients at a given dose level. The MTD will be declared as the highest dose level 
tested below that particular dose level. Based on the MTD assessment results, additional doses 
and schedules may be opened as required to define the dose and schedule of the RP2D. 
Please also see Figure 4.2. 
Figure 4.2: Part A: SOT102 dosing schedule 
 
Patients with gastric/GEJ cancer were treated according to the same dosing schedule. No 
patients with gastric/GEJ cancer will be enrolled in the current amended trial (for details see 
the IB). 
4.1.2.1 Screening period 
Patients will be screened within a period of not more than 21 days, which will start when the 
informed consent form (ICF) has been signed and end on the day before day 1 of cycle 1. All 
Protocol-required screening laboratory tests must be done within 7 days before day 1 of cycle 1. 
Patients may be rescreened once. Rescreening is subject to the same requirements as screening, 
including a new ICF signature. 
A sample of tumor tissue is required during screening for confirmation of CLDN18.2 
expression and measurement of CLDN18.2 levels (per immunohistochemistry [IHC]). 
4.1.2.2 DLT evaluation period 
The DLT evaluation period will be 28 days starting from day 1 of cycle 1 of SOT102 treatment. 
4.1.2.3 Continued treatment period 
During the treatment period, the trial assessments will be performed as outlined in the Schedule 
of activities. Trial interventions will be administered as described in section 6. 
Patients without DLT during the DLT evaluation period will continue treatment with SOT102 
monotherapy until any of the criteria for treatment discontinuation are met (see section 7.1). 

 
 
 
 
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4.1.2.4 Follow-up period 
Every effort should be made to monitor all AEs and concomitant medications for 30 days after 
the final dose of SOT102; whenever possible, all patients will come to the clinic 30 (+5) days 
after the final dose of SOT102. 
Trial participation of patients who discontinue SOT102 therapy after progression of the disease 
will end by the Follow-up visit 30 (+5) days after the final dose of SOT102. 
Patients who discontinue SOT102 therapy prior to progression of the disease will continue to 
have regular efficacy (tumor) assessments until disease progression or until the start of a new 
anticancer therapy unless patients withdraw their consent. Trial participation of these patients 
will end either by the Follow-up visit 30 (+5) days after the final dose of SOT102 or by the last 
efficacy (tumor) assessment, whichever occurs later. 
In addition, the following events must be collected until disease progression or start of new 
anticancer therapy and monitored via phone calls every 6 weeks (±2 weeks) during the follow-
up period: 
• AEs considered as having a suspected causal relationship to SOT102 per the investigator’s 
judgment (including collection of any concomitant medications) 
4.1.3 
Part B (SOT102 combined with first-line SoC treatment, dose escalation) 
In Part B, patients with CLDN18.2-positive pancreatic adenocarcinoma will be treated with 
escalating doses of SOT102 given once every 14 days via the IV route over 45 (±15) minutes. 
If medically indicated, an extension of the infusion time up to 120 minutes is allowed. In this 
case, the sponsor must be informed. However, a total duration of 120 minutes should not be 
exceeded. SOT102 will be administered in combination with first-line SoC treatment as 
follows: 
• Nab-paclitaxel (125 mg/m2) will be given as a 30- to 40-minute infusion followed by 
gemcitabine (1000 mg/m2) given as a 30-minute infusion on days 1, 8, and 15. This 
treatment will be repeated every 28 days.6 
Hematologic growth factor support is allowed as medically indicated and must be documented. 
SOT102 will be administered first and upon completion of the SOT102 infusion, patients will 
be observed for any acute side effects for 120 minutes. After the observation period, first-line 
SoC treatment will be administered. 
If the SoC treatment needs to be discontinued for medical reasons that do not fulfill the criteria 
for trial treatment discontinuation, single-agent therapy with SOT102 will continue until any 
of the trial treatment discontinuation criteria are met (see section 7.1). 
Part B will start once monotherapy SOT102 dose level 3 in Part A is successfully completed 
and is safe. The starting dose of SOT102 in Part B will be Part A dose level 1. 
If an MTD in Part A is reached before dose level 3, then the starting dose of SOT102 in Part B 
will be decided based on review of all available safety/PK data. 
The Part B SOT102 dose levels will stay within the safe dose levels of SOT102 monotherapy 
from Part A. Under no circumstances will the Part B SOT102 dose levels exceed the highest 
dose deemed safe in Part A. 
Dose escalation will follow a modified Fibonacci scheme. Adjustments of the planned dose 
levels and dose increments will be considered by the DEC. 

 
 
 
 
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SOT102 dose escalation in combination with first-line SoC treatment will continue until DLTs 
are observed in ≥2 DLT-evaluable patients at a given dose level. The MTD will be declared as 
the dose level below that particular dose level. Based on the MTD assessment results, 
additional doses and schedules may be opened as required to define the dose and schedule of 
the RP2D. Please also see Figure 4.4. 
Figure 4.4: Part B pancreatic: SOT102 and first-line SoC treatment dosing schedule 
 
Patients with gastric/GEJ cancer were treated according to the same dosing schedule, with the 
SoC as follows: 
• Nivolumab8 (240 mg) will be given as a 30-minute infusion followed by oxaliplatin (85 
mg/m2) given as a 2-hour infusion and leucovorin (400 mg/m2) given as a 30-minute 
infusion, followed by a 5-FU bolus of 400 mg/m2 followed by 2400 mg/m2  
5-FU given as a 46-hour continuous infusion (mFOLFOX6).7 This treatment will be 
repeated every 14 days. 
No patients with gastric/GEJ cancer will be enrolled in the current amended trial (for details 
see the IB). 
4.1.3.1 Screening period 
Patients will be screened within a period of not more than 21 days, which will start when the 
ICF has been signed and end on the day before day 1 of cycle 1. All Protocol-required screening 
laboratory tests must be done within 7 days before day 1 of cycle 1. Patients may be rescreened 
once. Rescreening is subject to the same requirements as screening, including a new ICF 
signature. 
A sample of tumor tissue is required during screening for confirmation of CLDN18.2 
expression and measurement of CLDN18.2 levels (per IHC). 
4.1.3.2 DLT evaluation period 
The DLT evaluation period will be 28 days starting from day 1 of cycle 1 of SOT102 treatment. 
4.1.3.3 Continued treatment period 
During the treatment period, the trial assessments will be performed as outlined in the Schedule 
of activities. Trial interventions will be administered as described in section 6. 

 
 
 
 
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Patients without DLT during the DLT evaluation period will continue treatment with SOT102 
together with first-line SoC until any of the criteria for treatment discontinuation are met (see 
section 7.1). 
In case SOT102 needs to be discontinued for reasons other than disease progression, first-line 
SoC treatment will continue until any of the criteria for treatment discontinuation are met. If 
first-line SoC treatment needs to be discontinued for reasons other than disease progression, 
SOT102 treatment will continue until any of the criteria for treatment discontinuation are met 
(see section 7.1). 
4.1.3.4 Follow-up period 
Every effort should be made to monitor all AEs and concomitant medications for 30 days after 
the final dose of SOT102; whenever possible, all patients will come to the clinic 30 (+5) days 
after the final dose of SOT102. 
Trial participation of patients who discontinue SOT102 therapy after progression of the disease 
will end by the Follow-up visit 30 (+5) days after the final dose of SOT102. 
Patients who discontinue SOT102 therapy prior to progression of the disease will continue to 
have regular efficacy (tumor) assessments until disease progression or until the start of a new 
anticancer therapy unless patients withdraw their consent. Trial participation of these patients 
will end either by the Follow-up visit 30 (+5) days after the final dose of SOT102 or by the last 
efficacy (tumor) assessment, whichever occurs later. 
In addition, the following events must be collected until disease progression or start of new 
anticancer therapy and monitored via phone calls every 6 weeks (±2 weeks) during the follow-
up period: 
• AEs considered as having a suspected causal relationship to SOT102 per the investigator’s 
judgment (including collection of any concomitant medications) 
4.1.4 
Part C (SOT102 monotherapy, cohort expansion) 
Part C will commence once Part A has established an RP2D. Part C will be performed in 
patients with CLDN18.2-positive tumors: 
• Patients with CLDN18.2-positive pancreatic adenocarcinoma who have received at least 
one prior line of systemic therapy 
Patients will be treated with SOT102 monotherapy at the RP2D identified in Part A given once 
every 14 days via the IV route over 45 (±15) minutes. If medically indicated, an extension of 
the infusion time up to 120 minutes is allowed. In this case, the sponsor must be informed. 
However, a total duration of 120 minutes should not be exceeded. 
Please also see Figure 4.5. 
 
 

 
 
 
 
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Figure 4.5: Part C: SOT102 dosing schedule 
 
4.1.4.1 Screening period 
Patients will be screened within a period of not more than 21 days, which will start when the 
ICF has been signed and end at the time the patient is deemed eligible and enrolled. All 
Protocol-required screening laboratory tests must be done within 7 days before enrollment. 
Patients may be rescreened once. Rescreening is subject to the same requirements as screening, 
including a new ICF signature. 
A sample of tumor tissue is required during screening for confirmation of CLDN18.2 
expression and measurement of CLDN18.2 levels (per IHC). 
4.1.4.2 Treatment period 
During the treatment period, the trial assessments will be performed as outlined in the Schedule 
of activities. Trial interventions will be administered as described in section 6. 
Trial treatment should be initiated as soon as possible after the patient is deemed eligible and 
enrolled in the trial, but no later than 7 days after the enrollment. Patients will be treated with 
SOT102 until any of the criteria for treatment discontinuation are met (see section 7.1). 
4.1.4.3 Follow-up 
Every effort should be made to monitor all AEs and concomitant medications for 30 days after 
the final dose of SOT102; whenever possible, all patients will come to the clinic 30 (+5) days 
after the final dose of SOT102. 
Patients who discontinue SOT102 therapy prior to progression of the disease will continue to 
have regular efficacy (tumor) assessments until disease progression or until the start of a new 
anticancer therapy unless patients withdraw their consent. 
Patients will be followed up for survival every 3 months (±2 weeks) during year 1 and then 
every 6 months (±2 weeks) until the end of the trial. 
4.1.5 
Part D (SOT102 combined with first-line SoC treatment, cohort expansion) 
Part D will commence once Part B has established an RP2D. Part D will be performed in 
patients with CLDN18.2-positive tumors: 
• Patients with CLDN18.2-positive pancreatic adenocarcinoma 
Patients will be treated with SOT102 at the RP2D identified in Part B given once every 14 days 
via the IV route over 45 (±15) minutes. If medically indicated, an extension of the infusion 

 
 
 
 
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time up to 120 minutes is allowed. In this case, the sponsor must be informed. However, a total 
duration of 120 minutes should not be exceeded. SOT102 will be administered in combination 
with first-line SoC treatment as follows: 
• Nab-paclitaxel (125 mg/m2) will be given as a 30- to 40-minute infusion followed by 
gemcitabine (1000 mg/m2) given as a 30-minute infusion; on days 1, 8, and 15. This 
treatment will be repeated every 28 days. 
Hematologic growth factor support is allowed as medically indicated and must be documented. 
SOT102 will be administered first and upon completion of the SOT102 infusion, first-line SoC 
treatment will be administered. 
If the SoC treatment needs to be discontinued for medical reasons that do not fulfill the criteria 
for trial treatment discontinuation, single-agent therapy with SOT102 will continue until any 
of the trial treatment discontinuation criteria are met (see section 7.1). 
Please also see Figure 4.7. 
Figure 4.7: Part D pancreatic: SOT102 and first-line SoC treatment dosing schedule 
 
4.1.5.1 Screening period 
Patients will be screened within a period of not more than 21 days, which will start when the 
ICF has been signed and end at the time the patient is deemed eligible and enrolled. All 
Protocol-required screening laboratory tests must be done within 7 days before enrollment. 
Patients may be rescreened once. Rescreening is subject to the same requirements as screening, 
including a new ICF signature. 
A sample of tumor tissue is required during screening for confirmation of CLDN18.2 
expression and measurement of CLDN18.2 levels (per IHC). 
4.1.5.2 Treatment period 
During the treatment period, the trial assessments will be performed as outlined in the Schedule 
of activities. Trial interventions will be administered as described in section 6. 
Trial treatment should be initiated as soon as possible once the patient is deemed eligible and 
enrolled in the trial, but no later than 7 days after the enrollment. Patients will be treated with 
SOT102 in combination with first-line SoC treatment until any of the criteria for treatment 
discontinuation are met (see section 7.1). 

 
 
 
 
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In case SOT102 needs to be discontinued for reasons other than disease progression, first-line 
SoC treatment will continue until any of the criteria for treatment discontinuation are met. If 
first-line SoC treatment needs to be discontinued for reasons other than disease progression, 
SOT102 treatment will continue until any of the criteria for treatment discontinuation are met 
(see section 7.1). 
4.1.5.3 Follow-up period 
Every effort should be made to monitor all AEs and concomitant medications for 30 days after 
the final dose of SOT102; whenever possible, all patients will come to the clinic 30 (+5) days 
after the final dose of SOT102. 
Patients who discontinue SOT102 therapy prior to progression of the disease will continue to 
have regular efficacy (tumor) assessments until disease progression or until the start of a new 
anticancer therapy unless patients withdraw their consent. 
Patients will be followed up for survival every 3 months (±2 weeks) during year 1 and then 
every 6 months (±2 weeks) until the end of the trial. 
4.2 Scientific rationale for trial design 
Malignant transformation of the gastric/GEJ adenocarcinoma cell results in a disruption of cell 
polarity, causing CLDN18.2 to become exposed, which then becomes accessible to antibody 
binding. Moreover, CLDN18.2 is aberrantly expressed in malignancies of several other organs, 
such as pancreatic cancer. SOTIO hypothesizes that targeting predominantly CLDN18.2-
expressing tumor cells will avoid the toxic impact on tissue that lacks CLDN18.2 expression, 
exhibiting a favorable safety profile of SOT102, coupled with a strong cytotoxic effect of 
linked payload, leading to eradication of tumor cells and thus effective cancer control. Based 
on CLDN18.2 prevalence in the literature4,5,31 and sponsor’s internal IHC analysis, pancreatic 
adenocarcinoma was selected as a tumor type with sufficient likelihood of desired IHC 
positivity and an unmet clinical need for new treatments. 
The modular Protocol allows for development of SOT102 in pancreatic patients in advanced 
lines of therapy as well as exploring efficacy when combined with existing established first-
line SoC therapies. Initiation of the combination dose-finding part at the time of dose level 3 
of the SOT102 monotherapy is considered adequate to ensure that patients enrolled in the 
combination (with SoC) dose-finding part of the trial will not be exposed to unreasonable risk. 
The original intention of the trial was to investigate its objectives in two indications - 
gastric/GEJ cancer and pancreatic cancer. Following a reassessment of the benefit/risk ratio, it 
was decided by the sponsor to halt clinical development in gastric/GEJ cancer for the time 
being and proceed only with pancreatic cancer. For more details see the IB. 
4.3 Justification for dose 
4.3.1 
Starting dose and dose escalation steps in Part A 
The starting dose of the planned trial is based on 1/10 of the body surface-adjusted severely 
toxic dose in 10% of the animals (STD10) observed in rats and on 1/6 of the body surface-
adjusted highest non-severely toxic dose (HNSTD) observed in cynomolgus monkeys.32 
Considering current data from the rat and cynomolgus monkey dose range finding and Good 
Laboratory Practice toxicology studies with dose administrations on days 1, 15, and 29 (every 

 
 
 
 
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2 weeks), the STD10 in rats and the HNSTD in cynomolgus monkeys were determined to be at 
2 mg/kg and 0.6 mg/kg, respectively. The conversion according to body surface (allometric 
scaling factor of 6.2 for rats and 3.1 for and cynomolgus monkeys) and application of the safety 
margins (1/10 for rats and 1/6 for cynomolgus monkeys) result in both cases in a human starting 
dose of 0.032 mg/kg. Based on animal PK, exposure at this starting dose is predicted to be 
approximately 70 µg*h/ml in patients which is about 20-fold and 58-fold lower as observed at 
the HNSTD in cynomolgus monkeys and at the STD10 in rats, respectively. 
Based on in vivo mouse efficacy studies, strong antitumor activity was observed in patient-
derived xenograft models of both pancreatic and gastric carcinoma at the lowest tested dose of 
0.2 mg/kg. Based on the allometric scaling factor of 12 for mouse, the human equivalent would 
be 0.016 mg/kg and thus about 2-fold lower than the selected human starting dose. A 
comparison by means of exposure concludes that the exposure in mice was about 2.4-fold 
higher than the expected human exposure. Based on this, SOTIO expects the human starting 
dose of 0.032 mg/kg to be sufficiently safe with the potential for pharmacological activity and 
thus considers the starting dose relevant for the treatment of patients. 
The choice of dose escalation steps is justified through careful evaluation of toxicities and 
tolerability of all prior doses administered and is made after consideration of the totality of data 
available from both clinical and preclinical research. 
4.3.2 
Starting dose and dose escalation steps in Part B 
Part B of the trial will only be initiated once dose level 3 of Part A has been shown to be safe. 
The choice of the starting dose of SOT102 for Part B rests on the assumption that the difference 
of three dose levels between Part A and Part B provides an acceptable safety margin for patients 
about to receive the combination treatment with SoC. 
If an MTD in Part A is reached before dose level 3, then the starting dose of SOT102 in Part B 
will be decided based on the review of all available safety/PK data. 
Dose escalation steps in Part B are justified because SOT102 dose levels will stay within the 
safe dose levels of monotherapy SOT102 from Part A. Under no circumstances will the Part B 
SOT102 dose levels exceed the highest dose deemed safe in Part A. 
4.4 Trial and site start and closure 
The first act of recruitment is the signing of the ICF by the first patient, which will also be the 
trial start date. 
A patient is considered to have completed the trial if s/he has completed all periods of the trial, 
including follow-up calls. 
It is expected that the enrollment duration will be 21 months in Part A, 14 months in Part B, 
18 months in Part C, and 18 months in Part D. Patients who will respond to therapy will 
continue with treatment until any of the criteria for treatment discontinuation are met (see 
section 7.1). The planned overall trial duration is approximately 6 years. The trial will end 
when the last patient completes the last visit or procedure, including follow-up calls. 
The sponsor reserves the right to terminate the trial for medical reasons or any other reason at 
any time. If the trial is prematurely terminated or suspended, the sponsor will promptly inform 
the investigators/institutions, regulatory agencies, and institutional review board (IRB) / 
independent ethics committee (IEC; in the US) / ethics committee (EC; in the EU), or 

 
 
 
 
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equivalent committees (outside the US and EU) of the termination or suspension and the 
reason(s) for the termination or suspension. 
The investigator reserves the right to discontinue the trial should his/her judgment so dictate. 
If the investigator terminates or suspends the trial without prior agreement with the sponsor, 
the investigator must inform the institution, and the investigator/institution must promptly 
inform the sponsor and the IRB/IEC (in the US)/EC (in the EU)/equivalent committees (outside 
the US and EU) and provide the sponsor and the IRB/IEC (in the US)/EC (in the EU)/equivalent 
committees (outside the US and EU) with a detailed written explanation of the termination or 
suspension. 
 

 
 
 
 
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5 TRIAL POPULATION 
5.1 Inclusion criteria 
5.1.1 
Inclusion criteria applicable to all trial parts 
1. Age ≥18 years 
2. Written informed consent given prior to any trial-specific procedures 
3. Adequate organ function: 
3.1. Hematologic: Absolute neutrophil count ≥1.5×109/L, platelets ≥100×109/L, 
hemoglobin ≥9 g/dL 
3.2. Hepatic: Bilirubin ≤1.5× upper limits of normal (ULN), ALT and AST ≤2.5×ULN; in 
case of liver involvement: AST and ALT ≤5×ULN 
3.3. Renal: Creatinine clearance ≥60 mL/min calculated by Cockcroft-Gault formula (see 
section 10.3) 
3.4. Prothrombin time/international normalized ratio (INR) ≤1.5×ULN 
3.5. Albumin ≥3.0 mg/dL 
3.6. Proteinuria <1 g/24 hours 
3.7. Serum concentrations of potassium, magnesium, and calcium within normal range 
4. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 
5. Estimated life expectancy ≥3 months as per investigator’s assessment 
6. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and one 
of the following conditions applies: 
6.1. Not a woman of childbearing potential (WOCBP). A WOCBP is defined as fertile, 
following menarche and until becoming postmenopausal unless permanently sterile. 
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and 
bilateral oophorectomy. A postmenopausal state is defined as no menses for 
12 months without an alternative medical cause. A high follicle stimulating hormone 
level in the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or hormonal replacement therapy. 
However, in the absence of 12 months of amenorrhea, a single follicle stimulating 
hormone measurement is insufficient. 
6.2. A WOCBP who agrees to use a highly effective contraceptive method during the 
treatment period and for at least 9 months after the last dose of SOT102 or first-line 
SoC treatment (whichever occurs later) 
• WOCBP can only be included after a negative serum pregnancy test at screening. 
• Highly effective contraception includes: 
o Combined (estrogen- and progestogen-containing) hormonal contraception 
associated with inhibition of ovulation: 
▪ Oral 

 
 
 
 
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▪ Intravaginal 
▪ Transdermal 
o Progestogen-only hormonal contraception associated with inhibition of 
ovulation: 
▪ Oral 
▪ Injectable 
▪ Implantable 
o Intrauterine device 
o Intrauterine hormone-releasing system 
o Bilateral tubal occlusion 
o Vasectomized partner provided the partner is the sole sexual partner of the 
WOCBP trial participant and that the vasectomized partner has received 
medical assessment of the surgical success 
o Sexual abstinence is defined as refraining from heterosexual intercourse 
during the entire treatment period and for at least 9 months after the last dose 
of SOT102 or first-line SoC treatment. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the patient. 
7. Male patients must agree to use a condom during treatment and for 9 months after SOT102 
or first-line SoC treatment discontinuation. Male patients wishing to become a father 
during or after the trial should consider sperm preservation. WOCBP partner of male 
participant should use highly effective contraception methods for 9 months after SOT102 
or first-line SoC treatment discontinuation. 
8. Left ventricular ejection fraction (LVEF) ≥50% as determined by echocardiography or 
nuclear medicine methodology (multiple gated acquisition scanning [MUGA]) 
9. QTcF interval <450 msec on screening electrocardiogram (ECG) 
10. Patient is, in the judgment of the investigator, an appropriate candidate for experimental 
therapy 
11. Patient agrees not to participate in other interventional clinical trials while enrolled in the 
present trial (with the exception of survival follow-up period) 
12. All previous cancer therapies for locally advanced pancreatic cancer and any agents that 
have not received regulatory approval for any indication must have been discontinued prior 
to day 1 of cycle 1 (Note: not applicable in France, see section 10.8 ). Patients must have 
recovered from the acute effects of therapy and treatment-related toxicities must have 
reached grade ≤1 (exception: alopecia). Mitomycin-C and nitrosoureas must have been 
discontinued for ≥42 days. 
13. Adequate tumor tissue from biopsy or fine needle aspiration (FNA) (formalin-fixed 
paraffin-embedded [FFPE] blocks), or unstained slides from archival biopsy available or 
willingness to undergo a fresh tumor biopsy. Pancreatic tumor must have medium to high 
(2+3+) CLDN18.2 membranous staining on ≥75% of tumor cells by IHC. 

 
 
 
 
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Note: Tumor samples will be sent to a central laboratory for CLDN18.2 expression 
analysis. 
5.1.2 
Inclusion criteria specific to Part A 
14. Patient has advanced inoperable or metastatic disease 
15. Patient has received and/or has been determined to be intolerant of all SoC therapy known 
to confer clinical benefit 
16. Measurable or non-measurable disease according to RECIST 1.1 
17. Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced 
or metastatic 
5.1.3 
Inclusion criteria specific to Part B 
14. Patient has advanced inoperable or metastatic disease 
15. Patient must have at least one measurable lesion according to RECIST 1.1 
16. Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced or 
metastatic 
5.1.4 
Inclusion criteria specific to Part C 
13. Patient has advanced inoperable or metastatic disease 
14. Measurable disease according to RECIST 1.1. At least one measurable lesion must be 
outside of an earlier radiation field or must have progressed after radiation therapy. 
15. Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced or 
metastatic 
16. Must have received at least one prior systemic therapy for advanced or metastatic disease 
5.1.5 
Inclusion criteria specific to Part D 
14. Patient must have at least one measurable lesion according to RECIST 1.1. At least one 
measurable lesion must be outside of an earlier radiation field or must have progressed after 
radiation therapy. 
15. Histological or cytological evidence of adenocarcinoma of the pancreas that is advanced 
inoperable or metastatic 
5.2 Exclusion criteria 
5.2.1 
Exclusion criteria applicable to all trial parts 
1. Patient has received radiation therapy ≤14 days before day 1 of cycle 1 or has not recovered 
to grade ≤1 from treatment-related side effects 
2. Patient has been previously treated with the maximum cumulative dose of anthracyclines 
3. Severe preexisting medical conditions as per judgment of the investigator (e.g., active 
gastric or GEJ ulcer with or without bleeding, complete or incomplete gastric outlet 
syndrome with persistent or repetitive bleeding) 
4. History of interstitial pneumonitis or pulmonary fibrosis 

 
 
 
 
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5. Symptomatic central nervous system malignancy. Patients with asymptomatic or treated 
central nervous system metastases may be eligible if they are not treated with 
corticosteroids or anticonvulsants and the disease is stable for at least 60 days. 
6. Patient has peripheral sensory neuropathy grade ≥2 
7. Active infection requiring systemic therapy that is not clinically controlled before the 
signature of the ICF 
8. Patients with HIV will be eligible if: 
• CD4+ T-cell (CD4+) counts ≥350 cells/uL 
• they have no history of AIDS-defining opportunistic infections 
• they are not currently on HIV therapy 
Patients with hepatitis B will be eligible if: 
• there is serologic evidence of a resolved prior HBV infection (HBsAg-negative 
and anti-HBc–positive) 
Patients with hepatitis C will be eligible if: 
• they have completed curative antiviral treatment and have HCV viral load below 
the limit of quantification 
9. Alcohol or drug abuse as determined by the investigator 
10. Psychiatric condition or social situation that, in the opinion of the investigator, preclude 
that the patient is able to comply with trial requirements 
11. New York Heart Association class ≥2 heart failure, unstable angina, coronary angioplasty, 
coronary stenting, coronary artery bypass graft, myocardial infarction, cerebrovascular 
accident or hypertensive crisis within 6 months prior to day 1 of cycle 1 
12. History of major ventricular arrhythmias (e.g., ventricular tachycardia, ventricular 
fibrillation, Torsades de Pointes) 
13. History or family history of congenital long QT syndrome 
14. Bradycardia (<50 beats per minute) 
15. Family history of sudden cardiac death before age 50 
16. Major surgical intervention ≤28 days prior to ICF signature or incomplete wound healing 
after surgical intervention 
17. Time since last transfusion of RBCs ≤14 days before cycle 1 day 1 
18. Hypersensitivity or intolerance to any component of trial intervention 
19. Vaccination with a live or live-attenuated vaccine within 30 days prior the first dose of 
trial interventions; the full series (e.g., both doses of a two-dose vaccination series) should 
be completed prior to dosing if feasible and if delaying enrollment would not put the study 
subject at risk 

 
 
 
 
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5.2.2 
Exclusion criteria specific to Part A 
20. Any prior systemic therapy for metastatic cancer other than pancreatic cancer. Exception: 
stable disease under hormonal treatment for prostate cancer, stable disease under hormonal 
treatment for breast cancer. Prior therapy with fluoropyrimidine or gemcitabine as 
radiosensitizer during radiation therapy is allowed if such treatment is completed at least 
4 weeks prior to day 1 of cycle 1. Patients must have recovered to grade ≤1 from all side 
effects (exception: alopecia). 
5.2.3 
Exclusion criteria specific to Part B 
20. Patients have received any systemic therapy for metastatic disease. Neoadjuvant and/or 
adjuvant therapy for pancreatic cancer is allowed if completed ≥3 months prior to day 1 of 
cycle 1 AND patients must have recovered to grade ≤1 from all side effects (exception: 
alopecia). Prior therapy with fluoropyrimidine or gemcitabine as radiosensitizer during 
radiation therapy is allowed if such treatment is completed at least 4 weeks prior to day 1 
of cycle 1. Patients must not have received any prior systemic therapy for metastatic cancer 
other than pancreatic cancer. Exception: stable disease under hormonal treatment for 
prostate cancer, stable disease under hormonal treatment for breast cancer. 
21. Patients with contraindications to any component of the first-line SoC treatment 
22. Patients with clinically active inflammatory bowel disease 
23. Patients more clinically suitable (e.g., with BRCA1/2 mutation) to receive treatment with 
leucovorin 
calcium, 
fluorouracil, 
irinotecan 
hydrochloride, 
and 
oxaliplatin 
(FOLFIRINOX) as compared to nab-paclitaxel and gemcitabine according to the 
investigator’s opinion 
5.2.4 
Exclusion criteria specific to Part C 
20. Any prior systemic therapy for cancer other than pancreatic cancer. Exception: stable 
disease under hormonal treatment for prostate cancer, stable disease under hormonal 
treatment for breast cancer. Patients must have recovered to grade ≤1 from all side effects 
(exception: alopecia). 
5.2.5 
Exclusion criteria specific to Part D 
20. Patients have received any systemic therapy for metastatic disease. Neoadjuvant and/or 
adjuvant systemic therapy for pancreatic cancer respectively is allowed if completed ≥3 
months prior to day 1 of cycle 1 AND patients must have recovered to grade ≤1 from all 
side effects (exception: alopecia). Prior therapy with fluoropyrimidine or gemcitabine as 
radiosensitizer during radiation therapy is allowed if such treatment is completed at least 
4 weeks prior to day 1 of cycle 1. Patients must not have received any prior systemic 
therapy for metastatic cancer other than pancreatic cancer. Exception: stable disease under 
hormonal treatment for prostate cancer, stable disease under hormonal treatment for breast 
cancer. 
21. Patients with contraindications to any component of the first-line SoC treatment 
22. Patients with clinically active inflammatory bowel disease 

 
 
 
 
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24. Patients more clinically suitable (e.g., with BRCA1/2 mutation) to receive treatment with 
FOLFIRINOX as compared to nab-paclitaxel and gemcitabine according to the 
investigator’s opinion 
5.3 Lifestyle considerations 
5.3.1 
Meals and dietary restrictions 
Star fruit and grapefruit juice showed inhibition of cytochrome P3A (CYP3A), St. John’s wort 
showed induction thereof. Therefore, co-administration of SOT102 with these foods should be 
avoided. 
5.3.2 
Contraception 
SOT102 or any of its components may have adverse effects on a fetus in utero. Furthermore, 
it is not known if SOT102 has transient adverse effects on the composition of sperm. 
Patients should be informed that taking the trial medication may involve unknown risks to the 
fetus (unborn baby) if pregnancy was to occur during the trial. If there is any concern whether 
a patient of childbearing potential will reliably comply with the requirements for contraception, 
that patient should not be entered into the trial. 
Please also see section 5.1. 
5.3.3 
Use in nursing women 
It is unknown whether SOT102 or any of its components are excreted in human milk. Since 
many drugs are excreted in human milk, and because of the potential for serious adverse 
reactions in the nursing infant, patients who are breastfeeding are not eligible for enrollment. 
Please also see section 5.1. 
5.4 Screen failures 
Screen failures are defined as patients who consent to participate in the clinical trial by signed 
ICF but fail to meet the eligibility criteria and are not subsequently enrolled into the trial. A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
failure patients to meet the Consolidated Standards of Reporting Trials publishing requirements 
and to respond to queries from regulatory authorities. Minimal information includes 
demography, reason for screen failure, and AE/SAE as listed in section 8.3.2. Screening 
assessments, including laboratory tests, may be repeated, if necessary, provided they are carried 
out within the timelines defined for the screening period. Patients who fail screening due to 
any reason may be rescreened once. Patients who are rescreened are required to sign a new 
ICF. 
5.5 Criteria for temporarily delaying enrollment/administration of trial 
intervention 
See section 4.1.1 for information on staggered dosing in Part A and Part B. 
If a patient experiences an immediately life-threatening or fatal DLT at any dose level (Part A 
and Part B) or a life-threatening or fatal SAE considered by the investigator to have a suspected 
causal relationship to SOT102 (i.e., excluding events unequivocally related to cancer) or if 

 
 
 
 
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>30% of the treated patients discontinue because of toxicities considered by the investigator to 
be related to SOT102, the dosing of all patients in the trial will be temporarily stopped until the 
independent data monitoring committee (IDMC; or DEC for dose escalation parts only) have 
reviewed the safety data and determined if it is safe to continue and at which dose. 

 
 
 
 
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6 TRIAL INTERVENTIONS AND CONCOMITANT THERAPY 
6.1 Trial interventions administered 
6.1.1 
SOT102 (all trial parts) 
SOT102 will be administered IV on day 1 of the 14-day cycle. The IV infusion will take 
45 (±15) minutes. If medically indicated, an extension of the infusion time up to 120 minutes 
is allowed. In this case, the sponsor must be informed. However, a total duration of 120 minutes 
should not be exceeded. One treatment cycle will be 14 days. 
Patients will receive premedication with corticosteroids (4 mg dexamethasone twice daily) the 
day before, the day of (at least one hour prior), and the day after each SOT102 administration. 
SOT102 will be supplied in a vial containing lyophilized powder to be reconstituted in water 
for injection and later diluted in an infusion bag or perfusor syringe containing saline. Also see 
section 6.2. SOT102 is to be administered in a hospital setting under supervision of the 
investigator. An intensive care facility and skilled specialists must be available. 
6.1.2 
First-line SoC treatment (Part B and Part D) 
6.1.2.1 Nab-paclitaxel/gemcitabine 
The doses of nab-paclitaxel/gemcitabine will be administered as follows: Nab-paclitaxel 
(125 mg/m2) will be given as a 30- to 40-minute infusion followed by gemcitabine 
(1000 mg/m2) given as a 30-minute infusion on days 1, 8, and 15. This treatment will be 
repeated every 28 days. Nab-paclitaxel/gemcitabine treatment will be administered after 
SOT102 administration on day 1 of each cycle. 
Both nab-paclitaxel and gemcitabine are commercially available. Always refer to the 
current/latest approved package inserts/US prescribing information (for the US) and the 
Summaries of Product Characteristics (SmPC; for the EU) for comprehensive treatment 
information including, but not limited to, treatment preparation and administration as well as 
full pharmacologic and safety information.26,27 
6.1.2.2 mFOLFOX6 and nivolumab 
For patients in Part B gastric/GEJ cohort who are continuing on SoC therapy, the SoC is 
administered as follows: 
The doses of mFOLFOX6 and nivolumab components are administered as follows: Nivolumab 
(240 mg) is given as a 30-minute infusion followed by oxaliplatin (85 mg/m2) given as a 2-
hour infusion and leucovorin (400 mg/m2) given as a 30-minute infusion, followed by a 5-FU 
bolus of 400 mg/m2 followed by 2400 mg/m2 5-FU given as a 46-hour continuous infusion 
(mFOLFOX6). This treatment is repeated every 14 days. mFOLFOX6 and nivolumab 
treatment is administered after SOT102 administration on day 1 of each cycle. 
All products that comprise the mFOLFOX6 and nivolumab regimen are commercially 
available. Nivolumab is to be used as per the approved label in the respective country. Always 
refer to the current/latest approved package inserts/US prescribing information (for the US) 
and the SmPCs (for the EU) for comprehensive treatment information including, but not limited 
to, treatment preparation and administration as well as full pharmacologic and safety 
information.9,25,28-30 

 
 
 
 
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6.1.3 
Investigational medical device 
A medical device manufactured for the sponsor by Roche Tissue Diagnostics provided for use 
in this trial is Roche Tissue Diagnostics CLDN18.2 IHC Clinical Trial Assay. All device 
deficiencies (including malfunction, use error and inadequate labelling) shall be documented 
and reported by the investigator throughout the trial and appropriately managed by the sponsor. 
6.2 Preparation, handling, storage, accountability 
The Pharmacy Manual contains specific instructions for preparation and administration of the 
SOT102 dose. 
SOT102 will be provided by the sponsor as clinical open-labeled supply, labeled in accordance 
with text that is fully compliant with each participating country’s regulations. The primary and 
secondary label will be translated into the required language(s) for each of those countries. 
SOT102 shall be stored in accordance with the labeled storage conditions. Temperature 
monitoring is required at the storage location to ensure that SOT102 is kept within  
2-8°C. The investigator is responsible for ensuring that the temperature is monitored 
throughout the total duration of the trial and that records are maintained; the temperature should 
be monitored continuously using either an in-house validated data acquisition system, a 
mechanical recording device such as a calibrated chart recorder, or manually, so that minimum 
and maximum thermometric values over a specific time period can be recorded and retrieved 
as required. 
The investigator or designee must confirm appropriate temperature conditions were maintained 
during transit for all trial interventions received and any discrepancies are reported and resolved 
before use of the trial interventions. 
Only patients enrolled in the trial may receive trial interventions and only authorized site staff 
may supply or administer the trial interventions. All trial interventions must be stored in a 
secure, environmentally controlled, and monitored (manually or automatically) area in 
accordance with the labeled storage conditions with access limited to the investigator and 
authorized site staff. 
The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for trial intervention accountability, reconciliation, and record maintenance (i.e., 
receipt, reconciliation, and final disposition records). 
Further guidance and information for the final disposition of unused trial interventions are 
provided in the Pharmacy Manual. 
6.3 Measures to minimize bias: randomization and blinding 
This is an open-label trial; the treatment will not be blinded. 
6.4 Trial intervention compliance 
Treatment for each patient will be recorded in the eCRF during the trial. Clinical research 
associates (CRAs) will review treatment compliance during site visits and at the completion of 
the trial. 
Medication errors and uses outside what is foreseen in the Protocol, including misuse and abuse 
of SOT102, must be recorded. An underdose or overdose of SOT102 treatment of 10% over or 
under the dose as defined in section 4.3 needs to be reported. 

 
 
 
 
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6.5 Dose modification 
6.5.1 
Dose modification and toxicity management for SOT102 
No dose reduction or treatment delay of SOT102 will be allowed for any dose levels in Part A 
and Part B in SOT102 cycles 1 and 2. Under exceptional logistics circumstances, and only 
following a discussion with the sponsor, a treatment delay of +1 day is allowed in Part A and 
Part B in SOT102 cycles 1 and 2. In Part A and Part B, starting from cycle 6, SOT102 can be 
administered on day 1 ±1 day. 
In a patient who develops DLT, treatment will be discontinued unless the investigator 
determines that the patient has a clear and demonstrable clinical benefit from treatment at the 
same time. Further continuation of therapy in these specific circumstances must be discussed 
with the sponsor and an adequately customized dose must be agreed upon between the 
investigator and the sponsor. Treatment delay or reduction is only possible after a discussion 
with the sponsor. 
In case a patient develops a grade ≥3 AE or an intolerable persistent grade 2 AE after the DLT 
evaluation period in Part A and Part B, the treatment will be delayed. If the AE reverts to grade 
≤1 within 4 weeks from the day of the previous dose of SOT102, the treatment may resume, 
otherwise the treatment needs to be discontinued permanently. In case the patient develops a 
grade 4 AE, the treatment needs to be discontinued permanently. 
In Part C and Part D, in case a patient develops a grade ≥3 AE or an intolerable persistent grade 
2 AE anytime during the treatment period, the treatment will be delayed. If the AE reverts to 
grade ≤1 within 4 weeks from the day of the previous dose of SOT102, the treatment may 
resume, otherwise the treatment needs to be discontinued permanently. 
Once the treatment is resumed, the next dose of this patient will be reduced initially by 25% of 
the initial dose. If the AE will not resolve or will worsen again, the next dose will be further 
reduced by 50% of the initial dose. If the AE will still not resolve or will worsen, the treatment 
needs to be discontinued permanently. 
In Part C and Part D, starting from cycle 2, SOT102 may be administered on day 1 ±1 day. 
In case a patient develops significant toxicities and at the same time has a demonstrable clinical 
benefit from treatment, further continuation of therapy must be discussed with the sponsor and 
an adequately customized dose must be agreed upon between investigator and sponsor. 
Treatment delay or reduction is only possible after a discussion with the sponsor. 
Any treatment-related toxicity will be managed by concomitant medication (as appropriate) or 
by SoC treatment delay, treatment discontinuation, or a combination of these. 
6.5.2 
Dose modification and toxicity management for first-line SoC treatment 
Treatment modifications of first-line SoC treatment (Part B and Part D) are allowed according 
to the approved labels or as per local or institutional guidelines.9,25-30 In Part B, starting from 
cycle 6, first-line SoC treatment can be administered on day 1 ±1 day. In Part D, starting from 
cycle 2, first-line SoC treatment can be administered on day 1 ±1 day. In case an AE cannot be 
clearly attributed to any of the first-line SoC treatment agents, treatment modifications will 
follow the general principle: 

 
 
 
 
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In the occurrence of grade ≥3 AE, both the treatment with SOT102 and the first-line SoC 
treatment will be delayed, while on the second occurrence of grade ≥3 AE, SOT102 will be 
discontinued permanently. 
If the SoC treatment needs to be discontinued for medical reasons that do not fulfill the criteria 
for trial treatment discontinuation, single-agent therapy with SOT102 will continue until any 
of the trial treatment discontinuation criteria are met (see section 7.1). 
6.6 Continued access to trial intervention after the end of the trial 
No trial intervention is planned to be administered to patients after the end of the trial. 
6.7 Treatment of overdose 
Side effects following administration of SOT102 during the preclinical studies appeared to be 
dose related. Exceeding the prescribed dose in the trial may be associated with increased 
toxicity. Symptoms which persist after stopping the treatment with SOT102 should be closely 
monitored and treated supportively. 
6.8 Concomitant therapy 
The investigator should instruct patients to notify the investigational site about any new 
medications taken since screening. All medications and non-drug therapies (e.g., blood 
transfusions) administered after screening must be listed in the eCRF. 
Concomitant administration of live or live-attenuated vaccines are not allowed within 30 days 
prior to the first dose of trial interventions, during the trial and within 90 days after the last 
dose of SOT102 and/or SoC, whichever is later. Note: Inactivated vaccines are allowed. 
6.8.1 
Rescue medication and supportive care 
Supportive care can be provided based on investigator judgment according to local institutional 
guidelines. For first-line SoC treatment, the approved local labels must be followed.9,25-30 In 
principle, only authorized medicinal products should be used as auxiliary medicinal products 
(AxMP) in clinical trials. In exceptional cases where no authorized AxMP are available in the 
EU or in other countries, or when it cannot reasonably be expected to use an authorized AxMP 
for the acute treatment of serious health problems in trial subjects in the context of management 
of toxicities, non-authorized medicinal products may be used on the basis of clinical 
management guidelines. 
6.8.2 
Drug-drug interaction potential 
In vitro studies addressing cytochrome P450 (CYP450) activities, and their inhibition identified 
 and 
-linker containing metabolites as potential inhibitors of CYP3A4 and 
CYP2D6, respectively. However, based on the absence or low abundance of these structures 
in animals and based on the potentially achievable concentrations following SOT102 
administration, inhibition of CYP3A4 and CYP2D6 in patients seems unlikely. Please refer to 
the IB for more details. 
6.8.3 
Medications requiring special caution 
Considering the potential risk, caution should be exercised when administering SOT102 with 
medications known to inhibit either CYP3A4 or CYP2D6. Caution should be also exercised 

 
 
 
 
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when administering SOT102 with medications known as substrates of CYP2D6 and CYP3A. 
Caution should be also used with medications known to or with the potential to prolong 
QT/QTc interval. For an overview of some of the medications see section 10.5. 
Since 
 is a substrate of CYP2C9 as well, use of concomitant medications that are 
known inhibitors or inducers of CYP3A4 or CYP2C9 should be avoided in Part A and B in 
order to minimize any effect on exposure to 
 or 
-linker-containing 
metabolites. 
Patients in Part C and D receiving SOT102 and comedications that are known inhibitors or 
inducers of CYP3A4 or CYP2C9 need to be closely monitored for AEs. For an overview of 
some of the medications see section 10.5. 
Given the nephrotoxic properties of NSAIDs or other potentially nephrotoxic medications, 
these should be used with caution and at the discretion of the investigator during treatment with 
SOT102. 
Caution should be used with the following medications when administering first-line SoC 
treatment. 
6.8.3.1 mFOLFOX6 
For patients in Part B gastric/GEJ cohort who are continuing on SoC therapy, concomitant use 
of drugs known to prolong the QT/QTc interval is prohibited during the trial. Some of the 
medications that may prolong the QT interval are listed in section 10.5. 
Various agents have been reported to biochemically modulate the antitumor efficacy or toxicity 
of fluorouracil, such as: 
• Methotrexate 
• Folic acid antagonists (e.g., cotrimoxazole, pyrimethamine) 
• Anti-epileptic substances (phenobarbital, primidone, phenytoin and succinimides) 
• Purines (inosine, guanosine, guanosine-5'-phosphate and deoxyinosine), pyrimidines 
(thymidine, uridine and cytidine), and antimetabolites (e.g., hydroxyurea) 
• Tamoxifen, interferon, phosphonoacteyl-L-aspartate, allopurinol, dipyridamole 
• Warfarin 
• Brivudine and sorivudine 
• Levamisole 
• Phenytoin 
6.8.3.2 Nab-paclitaxel 
Caution should be exercised when administering medications known to induce or inhibit either 
cytochrome P2C8 (CYP2C8) or cytochrome P3A/P3A4 (CYP3A/CYP3A4). In the EU (per 
nab-paclitaxel EU SmPC), CYP2C8 and CYP3A4 inducers are not recommended in cohorts 
including nab-paclitaxel. Caution should be also used with medications known to or with the 
potential to prolong QT/QTc interval. For an overview of some of the medications see section 
10.5 and also the EU SmPC.26 
 

 
 
 
 
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7 DISCONTINUATION OF TRIAL INTERVENTION AND PATIENT 
DISCONTINUATION/WITHDRAWAL 
7.1 Discontinuation of trial intervention 
Patients will be discontinued from trial treatment (SOT102 or SOT102/first-line SoC treatment 
respectively) for any of the following events: 
• Radiographic disease progression per RECIST 1.1 
• Clinical disease progression (investigator assessment) 
• AE (intercurrent illness or trial treatment-related toxicity) that would, in the judgment of 
the investigator, affect assessments of clinical status to a significant degree or require 
discontinuation of trial treatment 
• During the DLT evaluation period, any DLT/DLT-equivalent event 
• Following the DLT evaluation period: any DLT-like event, specifically grade 2 or higher 
serum creatinine elevation, grade 2 or higher proteinuria 
• Patient may withdraw from the trial at any time for any reason; the investigator must make 
reasonable effort to determine the reason for this decision and record it in source 
documentation of the patient 
• Death 
• Pregnancy 
• Patient non-compliance 
• Lost to follow-up 
• Trial terminated by the sponsor 
• If, in the opinion of the investigator, continuation of treatment is no longer in the best 
interest of the patient 
See also section 5.5. 
7.2 Patient discontinuation/withdrawal from the trial 
A patient may elect to withdraw from the trial at any time for any reason. All patients who 
withdraw from the trial are to complete the last Follow-up visit as indicated in the Schedule of 
activities. 
A patient who has ceased to return for visits will be followed up by mail, phone, or other means 
to gather information such as the reason for failure to return, the status of treatment compliance, 
the presence or absence of AEs, and clinical courses of signs and symptoms. 
7.3 Lost to follow-up 
A patient will be considered lost to follow-up if s/he repeatedly fails to return for scheduled 
visits and is unable to be contacted by the trial site. 
 

 
 
 
 
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The following actions must be taken if a patient fails to return to the clinic for a required trial 
visit: 
• The site must attempt to contact the patient and reschedule the missed visit as soon as 
possible and counsel the patient on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the patient wishes to and/or should continue in the 
trial. 
• Before a patient is deemed lost to follow-up, the investigator or designee must make every 
effort to regain contact with the patient (where possible, three telephone calls and, if 
necessary, a certified letter to the patient’s last known mailing address or local equivalent 
methods). These contact attempts will be documented in the patient’s medical record. 
• Should the patient continue to be unreachable, s/he will be considered to have withdrawn 
from the trial.  
 

 
 
 
 
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8 TRIAL ASSESSMENTS AND PROCEDURES 
Trial procedures and their timing are summarized in the Schedule of activities. Protocol 
waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the sponsor immediately upon occurrence 
or awareness to determine if the patient should continue or discontinue trial interventions. 
Adherence to the trial design requirements, including those specified in the Schedule of 
activities, is essential and required for trial conduct. 
All screening evaluations must be completed and reviewed to confirm that potential patients 
meet all eligibility criteria. The investigator will maintain a screening log to record details of 
all patients screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 
Procedures conducted as part of the patient’s routine clinical management (e.g., CT scans) and 
obtained before signing of the ICF may be utilized for screening or baseline purposes provided 
the procedures met the Protocol-specified criteria and were performed within the time frame 
defined in the Schedule of activities. 
At screening, demography information will be collected (age at screening, gender, race, and 
ethnicity). Relevant medical and surgical history must be available and noted in the eCRF. 
Information on history of current malignancy will be collected, including histology/cytology, 
initial diagnosis date, details about previous systemic and non-systemic treatment together with 
the associated disease response and date of last disease progression, and any prior 
mutations/genetic analysis. Other baseline assessments will be done as defined in the Schedule 
of activities. 
8.1 Efficacy assessments 
Tumor assessments will be performed by investigators and assessed per RECIST 1.1 for all 
tumor indications. Radiology images acquired for tumor assessments will be provided to a 
dedicated vendor for blinded independent assessment as per RECIST 1.1, for all indications in 
Part C and Part D. 
8.1.1 
Radiologic evaluation of disease 
Disease response and disease progression will be evaluated in this trial using RECIST 1.1 
criteria by contrast-enhanced computed tomography (CT) scans of the chest, abdomen, and 
pelvis and/or magnetic resonance imaging (MRI). Other areas might be assessed during the 
course of the trial, if clinically indicated (e.g., brain). The imaging method used at baseline 
should be used throughout the trial unless otherwise medically indicated. 
Contrast (IV and oral) enhanced spiral CT is a preferred imaging modality. In case of 
hypersensitivity to contrast medium, the thoracic CT should be performed without IV contrast 
medium. In such cases, the abdomen and pelvis should be imaged by MRI, or patients can 
undergo a desensitization procedure, or be pre-medicated as per local guideline. 
CT may be replaced by MRI during the course of the trial for patients with contraindications 
to the administration of contrast agents, or due to other medical reasons, at the discretion of the 
investigator. 

 
 
 
 
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The first scan after the initiation of trial interventions should be performed at 6 weeks (±2 
weeks) from cycle 1 day 1. Subsequent tumor scans should be performed every 6 weeks (±2 
weeks) or more frequently if clinically indicated, as per Schedule of activities. 
The baseline disease assessment will be performed before the initiation of trial treatment and 
response assessments will be performed as indicated in the Schedule of activities. 
8.1.2 
Quality of life assessments (only in Part C and Part D) 
To determine the effect of trial intervention on the QoL, patient-reported questionnaires 
EORTC QLQ-C30 and EORTC QLQ-PAN26 for patients with pancreatic cancer will be 
utilized for this trial. 
A baseline assessment will be done at screening. Patients will complete the questionnaires on 
day 1 of cycles 1 and 4 and at the Follow-up visit 30 days after the last dose of SOT102, as 
indicated in the Schedule of activities. 
EQ-5D-3L questionnaires will be completed. A baseline assessment will be done at screening, 
and subsequent assessments will be completed by patients every other SOT102 treatment cycle, 
until the completion of SOT102 therapy. Afterwards, the frequency will be every 16 weeks 
during year 1 and then every 6 months until the end of trial. 
If feasible, the questionnaires should be completed before trial procedures and/or SOT102 
administration. 
8.1.3 
Survival information assessments (only in Part C and Part D) 
Survival information will be collected as indicated in the Schedule of activities. 
8.2 Safety assessments 
Safety monitoring of the patients during the trial will include assessments, physical 
examinations, vital signs monitoring, and laboratory tests as described below. In Part A and 
Part B, the DLT evaluation period is 28 days starting from day 1 of cycle 1 of SOT102 
treatment. After that period and in Part C and Part D, the assessments, examinations, and 
laboratory tests will continue as specified in the Schedule of activities. 
If patients feel unwell at any point in time during the trial after being discharged from the 
hospital, they should contact their trial investigator. 
All assessments will be carried out in accordance with standard local institutional practice, 
unless otherwise stated in the Protocol. 
8.2.1 
Physical examinations, body height, weight, and surface area, ECOG 
performance status 
General physical examination with organ/system-specific physical examination will be carried 
out by a licensed physician (or the physician’s assistant or a nurse practitioner). 
For screening and subsequent visits, a complete physical examination, laboratory tests as well 
as determination of body height, weight, and surface area will be performed according to the 
Protocol schedule outlined in the Schedule of activities. 
ECOG performance status will be assessed at screening, during the trial, and at the Follow-up 
visit 30 days after the last dose of SOT102, as indicated in the Schedule of activities. 

 
 
 
 
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8.2.2 
Vital signs 
Vital signs will include body temperature, blood pressure (systolic and diastolic, after ≥15 
minutes of rest), and heart rate. See also section 8.2.3. 
8.2.3 
Special assessments on treatment days 
8.2.3.1 Cycle 1 day 1 
In cycle 1 of Part A and Part B, patients may be hospitalized for 24 hours after the first dose of 
SOT102 on day 1, or longer if clinically indicated, and will be closely observed for any AEs. 
Patients in Part C and Part D may be hospitalized only if clinically indicated. 
Vital signs (body temperature, heart rate, and systolic and diastolic blood pressure) will be 
documented at the following frequency at minimum, unless clinically required otherwise: 
• Prior to SOT102 administration 
• 15 (±5) minutes after the end of SOT102 infusion 
• 60 (±5) minutes after the end of SOT102 infusion 
8.2.3.2 Cycle 2 and onwards 
For the subsequent cycles in all trial parts, patients may be observed in the hospital following 
SOT102 administration if clinically indicated. 
During post-SOT102 observation, vital signs (body temperature, heart rate, and systolic and 
diastolic blood pressure) will be documented at the following frequency: 
• Prior to each SOT102 administration 
• 15 (±5) minutes after the end of SOT102 infusion 
• 60 (±5) minutes after the end of SOT102 infusion 
8.2.4 
Electrocardiography 
As outlined in the Schedule of activities, in Part A and Part B, an ECG will be done prior to 
SOT102 infusion and within 15 minutes after the end of SOT102 infusion in each cycle and as 
clinically indicated. In cycle 1 and 3 it will be additionally done 24 (±2) hours after the end of 
SOT102 infusion. The ECG collection plan in Part C and Part D, will be re-evaluated based on 
the emerging data from Part A and Part B. 
In the event of grade ≥3 corrected QT/QTc interval prolongation, close and appropriate ECG 
monitoring (continuously) in hospital will be conducted until a cardiologist’s opinion is issued. 
8.2.5 
Clinical safety laboratory assessments 
The standard clinical laboratory analyses are to be performed by a local laboratory. Results 
from laboratory analysis performed by a local laboratory will be documented in the eCRF. 
Results from laboratory analysis performed by a central laboratory will be provided to the 
sponsor, investigator (where applicable), or a contracted party. Details on the collection, 
handling, storage, and shipment of samples; and reporting of results by the 
laboratory/laboratories are provided to the investigator in the Laboratory Manual. More 
frequent evaluations may be performed at the investigator’s discretion if medically indicated; 
results of these additional tests should be recorded in eCRFs. 

 
 
 
 
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The sponsor must be provided with a copy of the certification and a tabulation of the normal 
ranges for the local laboratory/laboratories. Laboratory values that are out of reference ranges 
will be evaluated for their clinical significance. Laboratory abnormalities that do not meet the 
criteria of clinical relevance as judged by the investigator do not need to be reported as AEs. 
It should be noted that severity and seriousness are different criteria for the evaluation of AEs 
(please see more details in section 8.3.1.4). Therefore, grade 3 and grade 4 laboratory events 
(evaluated per NCI CTCAE [v5.0]) do not automatically classify as SAEs unless they meet 
seriousness criteria as per definition (see section 8.3.1.2). 
The timing of the laboratory tests to be done during the trial is specified in the Schedule of 
activities. From cycle 2 onwards in all trial parts, safety laboratory tests (as listed in the 
Schedule of activities) can be performed one day early before SOT102 or first-line SoC 
treatment scheduled dosing. 
An overview of laboratory tests to be performed is presented in section 10.4. 
8.2.6 
Left ventricular ejection fraction 
LVEF will be assessed using either echocardiography or nuclear medicine methodology 
(MUGA scan) in Part A and Part B at screening, every 2 months during the trial (± 2 weeks), 
and at the Follow-up visit 30 days after the last dose of SOT102; and in Part C, and Part D at 
screening and as clinically indicated. However, the method chosen needs to stay the same 
throughout the trial. 
8.2.7 
Esophagogastroduodenoscopy 
Esophagogastroduodenoscopy will be performed at screening and thereafter if clinically 
indicated. 
8.3 Adverse events, serious adverse events, and other safety reporting 
8.3.1 
Definitions 
8.3.1.1 Adverse events 
International Council for Harmonisation (ICH) guideline E2A defines an AE as any untoward 
medical occurrence in a patient or clinical investigation subject administered a pharmaceutical 
product and which does not necessarily have to have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (e.g., tachycardia, enlarged liver), 
symptom (e.g., nausea, chest pain), abnormal result of an investigation (e.g., laboratory 
finding), or disease temporarily associated with the use of a medicinal product, whether or not 
considered related to the medicinal product. 
According to the US Food and Drug Administration (21CFR312.32), an AE means any 
untoward medical occurrence associated with the use of a drug in humans, whether or not 
considered drug-related. 
8.3.1.2 Serious adverse events 
An SAE is any untoward medical occurrence that at any dose fulfills one or more of the 
following criteria: 
• Results in death 

 
 
 
 
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• Is immediately life-threatening 
• Results in persistent or significant disability/incapacity 
• Is a congenital anomaly/birth defect 
• Requires inpatient hospitalization or prolongation of existing hospitalization 
• Is another medically significant event defined as an event that may not be immediately life-
threatening or result in death or hospitalization but may jeopardize the patient or may 
require intervention to prevent any of the above listed outcomes 
8.3.1.3 Excluded events 
Hospitalization for the following reasons will not be regarded as serious (not immediately 
reportable): 
• Routine treatment or monitoring of the disease under study, including hospitalization due to 
trial-related procedures, not associated with any deterioration of the patient’s status 
• Elective or pre-planned treatment (before signing the ICF) for a preexisting condition that 
is unrelated to the disease under study and has not worsened since signing the ICF 
• Social reasons, respite care, and in the absence of a medical condition (e.g., for observational 
purposes without any intervention) 
8.3.1.4 Severity/intensity vs. seriousness 
ICH E2A: The term “severe” is often used to describe the intensity (severity) of a specific event 
(as mild, moderate, or severe myocardial infarction); the event itself, however, may be of a 
relatively minor medical significance (such as a severe headache). This is not the same as 
“serious”, which is based on patient/event outcome or action criteria usually associated with 
events that pose a threat to a patient’s life or functioning. Seriousness (not severity) serves as 
a guide for defining regulatory reporting obligations. 
8.3.2 
Time period and frequency for collecting AE, SAE, and other reportable safety 
event information 
Every effort should be made to collect all AEs (as listed below) from the date of the patient’s 
signing the ICF until 30 days after the final administration of SOT102: 
• (S)AEs regardless of their causal relationship to SOT102 
In addition, the following events must be collected in Part A and Part B until disease 
progression or start of new anticancer therapy during the follow-up period (i.e., beyond 30 days 
after the final administration of SOT102): 
• AEs considered as having a suspected causal relationship to SOT102 per the investigator’s 
judgment (including collection of any concomitant medications) 
Additionally, any SAE brought to the attention of an investigator at any time outside of the 
time period specified above must be reported immediately to the sponsor if the event is 
considered as having a suspected causal relationship to SOT102 per the investigator’s 
judgment. 
Pregnancies of the patient or patient’s female partner must be reported from the date of the 
patient’s signing the ICF up to 9 months after the final administration of SOT102. 

 
 
 
 
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8.3.3 
Method of detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the patient is the preferred method to inquire about 
AE occurrences. 
8.3.4 
Follow-up of AEs and SAEs 
The investigator assesses at each visit (or more frequently, if necessary) if there are any changes 
in AE diagnosis, severity, suspected causal relationship to clinical trial medication/procedure, 
interventions required to treat the event, and AE outcome. 
AEs are monitored (followed up) until resolution or until 30 days after the last dose of SOT102. 
All SAEs will be followed until resolution, stabilization (becoming a permanent condition), or 
the patient is lost to follow-up as defined in section 7.3. 
8.3.5 
Regulatory reporting requirements for SAEs 
Prompt notification of an SAE by the investigator to the sponsor is essential so that legal 
obligations and ethical responsibilities towards the safety of patients and the safety of an 
investigational medicinal product under clinical investigation are met. 
The sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of an investigational medicinal product under clinical 
investigation. The sponsor or designee will comply with country-specific regulatory 
requirements relating to safety reporting to the regulatory authority, IRB/IEC (in the US)/EC 
(in the EU)/equivalent committees (outside the US and EU), and investigators. 
An investigator who receives a periodic or expedited safety report (e.g., summary or listing of 
suspected unexpected serious adverse reactions [SUSARs]) or other specific safety information 
from the sponsor or designee will review and then file it along with the IB and will notify the 
IRB/IEC (in the US)/EC (in the EU)/equivalent committees (outside the US and EU), if 
appropriate according to local requirements. 
The sponsor will also ensure communication of SUSARs in association with SOT102 to all 
participating investigators in line with the national safety reporting requirements. 
Adverse reactions will be reported to the US FDA according to 21CFR312.32. 
8.3.6 
Pregnancy 
Pregnancy is not considered an (S)AE unless it meets any criteria for becoming serious (see 
the definitions in section 8.3.1.2). However, patients must inform the investigator of any newly 
identified pregnancy or pregnancy of their partners without delay. If a patient or patient’s 
female partner becomes pregnant while on treatment, the treatment must stop immediately. 
Consent to report information on the outcome of the pregnancy of patients or male patients’ 
partners needs to be obtained from the patients or male patient’s pregnant partners. 
Pregnancies will be monitored by the investigator to determine the outcome, including 
spontaneous abortion or voluntary termination, birth details, and the presence or absence of 
any birth defects, congenital abnormalities, or maternal and newborn complications. Every 
infant must be followed up for 2 months after delivery. 
Egg and sperm donation is not allowed during the treatment period and for at least 9 months 
after the last dose of SOT102. 

 
 
 
 
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8.3.7 
Assessing AEs 
Information about adverse reactions (causally related events) known for SOT102 will be found 
in the IB or will be communicated between IB updates in the form of a “Dear Investigator 
Letter”. 
8.3.7.1 Causality 
Investigators should use their knowledge of the patient, the circumstances surrounding the 
event, and an evaluation of any potential alternative causes to determine whether or not an AE 
is considered to be related to the trial intervention. 
The investigator needs to assess and report the causal relationship of any AE to: 
• SOT102 
• First-line SoC treatment (Part B and Part D only) 
• Other suspected cause(s) of the event (e.g., concurrent disease, concomitant medication, 
further-line therapy) 
This assessment is based on the investigator’s clinical judgment, taking into account all 
relevant information available at the time of AE reporting, including (but not limited to): 
• Temporal association of the event onset with administration of the medication/procedure 
• Known type of reaction for any of the administered medication 
• Disappearance or abating of symptoms when the medication is discontinued, or the dose is 
reduced 
• Reappearance of symptoms when the medication is re-administered 
• Event may or may not be caused by the patient’s health condition 
• Presence of risks or factors not related to trial treatment that are known to be associated 
with the occurrence of the event 
Causal relationship of all AEs will be classified as follows: 
• Not suspected: It is not plausible that the AE is caused by medication/procedure and a 
likely alternative explanation exists. 
No reasonable possibility of a causal or temporal relationship. 
• Suspected: It is plausible that the AE is caused by medication/procedure. 
Reasonable possibility of a causal relationship. 
For the purposes of safety reporting, “reasonable possibility” means there is evidence to 
suggest a causal relationship between one of the medications/procedures and the AE. 
8.3.7.2 Severity/intensity 
Severity or intensity of an AE must be assessed according to the NCI CTCAE, version 5.0. 

 
 
 
 
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8.3.8 
Reporting by the investigational site 
8.3.8.1 Adverse events 
Any AE (including SAEs), whether or not considered to be causally related to the trial 
medication and regardless of its seriousness, must be reported (described and recorded) in the 
AE section of the patient’s eCRF on an ongoing basis. 
Only clinically relevant abnormal laboratory values, vital signs, or examination abnormalities 
need to be documented as AEs. Whenever possible, a diagnosis rather than symptoms should 
be provided on the AE eCRF page (e.g., anemia instead of low hemoglobin). 
Clinically relevant here means: induce clinical signs or symptoms, require therapy (e.g., 
hematologic abnormality requiring treatment), require a change in trial medication(s), or 
require a change in the clinical trial schedule or per investigator’s discretion. 
Physical examination findings will be compared with the baseline status and any significant 
change, as assessed by the investigator, must be documented as an AE. 
A surgical procedure is not an AE but a therapeutic measure for a condition that necessitates 
surgery. Therefore, the condition for which the surgery is required must be reported as an AE. 
Any pre-planned surgery (i.e., planned before signature of the ICF) or other intervention 
permitted by this trial Protocol and the condition leading to that measure are not AEs. In such 
cases, the underlying condition needs to be documented in the patient’s medical history in the 
eCRF. 
Death itself is not an AE term but the outcome of an event, which needs to be described using 
medical terminology. Information about death will be captured on the respective eCRF page 
along with relevant details (date of death, immediate and underlying causes of death). 
8.3.8.2 Documenting in eCRFs 
The reported term needs to be a medical diagnosis or sign/symptom of the event, not a 
procedure. Each symptom in a constellation of symptoms should be listed separately if the 
investigator has not set a diagnosis. 
Fluctuations or re-occurrences of a condition, which are considered normal for the patient and 
are recorded in the patient’s eCRF medical history, do not need to be reported as an AE. 
However, if the condition deteriorates during the trial, it needs to be captured as an AE. 
If the same AE occurs repeatedly, it must be assessed and documented separately each time. 
If possible, each AE should be evaluated to determine: 
• Event term or a description of the AE in medical terms (not as reported by the patient) 
• Severity grade or intensity of the event as assessed by the investigator (1-5 according to the 
NCI CTCAE version 5.0) 
• Its causal relationship to SOT102, as assessed by the investigator (suspected; not suspected) 
• Its causal relationship to first-line SoC treatment (Part B and Part D only), as assessed by 
the investigator (suspected; not suspected) 
• Event duration, including onset date and end date 
• Action taken with SOT102 due to the reported event 

 
 
 
 
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• Action taken with first-line SoC treatment due to the reported event 
• Event seriousness (non-serious or serious AE) 
• Event outcome (resolved, resolved with sequelae, not resolved, resolving, fatal, unknown) 
8.3.8.3 Immediately reportable events 
The investigator or any investigational site staff must immediately (within 24 hours of 
awareness at the latest) notify/report to the sponsor’s designated Pharmacovigilance 
department any initial or medically relevant follow-up information about these events: 
• SAE 
• Pregnancy of the patient or patient’s female partner 
The initial notification can be made via email. This notification must be followed within an 
additional 24 hours by a written report (i.e., a completed SAE Report Form or Pregnancy Data 
Collection Form), providing all available information and a detailed narrative description. A 
formless notification (without a report form) is not required if the initial/follow-up information 
is reported on the appropriate form within 24 hours of knowledge. 
The investigator must not wait to receive additional information to fully document the event 
before notifying the sponsor’s designated Pharmacovigilance department primarily via the 
eCRF system; or via: 
Email: 
 
Follow-up information must be sent within the same timelines using the same contact details 
as outlined above. 
Additionally, refer to the Safety Reporting Instructions for Sites for information on how to 
report these events. 
Minimum notification/reporting requirements 
The following information must be provided for a valid notification/report: 
1. Identification of the notifying/reporting person (e.g., name of the reporter) 
2. Identification of the patient (e.g., patient number) 
3. Concerned trial treatment (SOT102) or clinical trial (e.g., SN201, CLAUDIO-01) 
4. Reason for notification/reporting (i.e., SAE, pregnancy of the patient or patient’s female 
partner) 
5. Event term 
In addition, providing an assessment of the causal relationship is necessary for 
comprehensive evaluation by the sponsor and potential regulatory submission. 
8.3.8.4 Report forms 
The SAE Report Form is primarily completed within the eCRF system for the trial and 
submitted to the sponsor’s designated Pharmacovigilance department. In case the eCRF system 
is not available/accessible, a paper SAE Report Form is filled out and sent to the sponsor’s 
designated Pharmacovigilance department (see details above). 

 
 
 
 
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For reporting of pregnancies, the paper Pregnancy Data Collection Form is to be used. 
Completion guidelines provide information on format and details of the information required. 
The originals of the paper report forms must be kept in the site trial file. 
The report forms need to be completed in English. 
All immediately reportable events from the investigational site to the sponsor’s designated 
Pharmacovigilance department (i.e., SAEs and patients’ or partners’ pregnancies) must also 
be recorded in the site’s source documentation and in the eCRF as appropriate. 
8.4 Pharmacokinetics 
Plasma concentrations of SOT102 will be tabulated and summarized by dose level, day, and 
time. 
The following PK parameters will be analyzed for total SOT102, conjugated SOT102, 
 
 
• Maximum concentration observed (Cmax) 
• Time of maximum concentration observed (Tmax) 
• Area under the curve (AUC) 
If possible, also the following will be analyzed: 
• Elimination half-life (t1/2) 
• Total body clearance 
• Volume of distribution 
• Accumulation ratio 
Further details will be specified in the Pharmacokinetic Analysis Plan or similar document as 
applicable. 
The actual date and time (24-hour clock time) of each sample will be recorded. 
Instructions on sample collection, handling, storage, and shipment of samples are detailed in 
the trial-specific Laboratory Manual provided to the trial site. 
8.5 Genetics 
Not applicable. 
8.6 Tumor biopsy 
A sample of tumor tissue is required during screening for assessment of CLDN18.2 levels (per 
IHC) in the tumor. Fresh tissue (in formalin-fixative) or archived formalin-fixed paraffin-
embedded (FFPE) tissue/FNA are acceptable. The tumor must be CLDN18.2-positive for the 
patient to be enrolled in the trial. IHC testing will be performed at a central laboratory. Refer 
to the Laboratory Manual for further details regarding biopsy collection and shipment. 

 
 
 
 
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Note: Given the length of time needed for IHC testing and the approximately 14-36% chance 
that a pancreatic cancer biopsy will meet the positivity threshold, this activity should be 
performed at the initiation of the screening period. 
8.7 Biomarkers 
No other biomarkers than CLDN18.2 will be assessed in this trial. 
8.8 Immunogenicity assessments 
Samples for anti-drug antibodies (ADAs) will be collected to assess SOT102 tolerance, 
correlation with PK, and potential AEs associated with ADAs against SOT102 and for the 
prediction of SOT102 ADA production. 
Instructions on sample collection, handling, storage, and shipment of samples are detailed in 
the trial-specific Laboratory Manual provided to the trial site. 
Samples will be stored for a maximum of 15 years (or according to local regulations) after the 
end of the trial at a facility selected by the sponsor to enable further analysis of immune 
responses to SOT102. 
8.9 Health economics 
Health economics parameters will not be evaluated in this trial. 
 

 
 
 
 
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9 STATISTICAL CONSIDERATIONS 
9.1 Statistical hypotheses 
Each trial part will be analyzed separately following its objectives. Each indication (cohort) in 
Part B, Part C, and Part D will be analyzed separately. 
The analyses will be descriptive. No formal testing of statistical hypotheses is planned in this 
open-label, single-arm trial. 
Descriptive statistics will be performed for continuous variables using the number of available 
observations, mean, standard deviation, median, minimum, and maximum. 
Categorical variables will be summarized as the number (percentage) of patients. 
Time-to-event variables will be analyzed using the Kaplan-Meier method. Median with log-
log confidence intervals (CIs), Q1 (25th percentile) and Q3 (75th percentile) will be presented. 
Statistical analyses will be performed using SAS software or other validated statistical software 
as required. Further details will be provided in the Statistical Analysis Plan. 
9.2 Analysis sets 
9.2.1 
Safety population 
All patients exposed to at least one dose of SOT102. All safety analyses will be performed on 
the safety population. 
9.2.2 
PK population 
All PK-evaluable patients. Evaluation of PK will be performed on the PK population. 
9.2.3 
DLT-evaluable patients (defined for Part A and Part B only) 
The DLT-evaluable patients are defined as in section 4.1.1. This population will be used to 
assess DLT incidence and to estimate the MTD. 
9.2.4 
Efficacy population 
All patients exposed to at least one dose of SOT102 who had at least one evaluable tumor 
assessment per RECIST 1.1 after the initiation of SOT102 treatment. This will be the main 
population for efficacy exploration. 
9.3 Statistical analyses 
9.3.1 
Part A (SOT102 monotherapy, dose escalation) and Part B (SOT102 
combination with first-line SoC treatment, dose escalation) 
9.3.1.1 Primary endpoint analysis 
The incidence of DLTs (in DLT-evaluable patients, see section 4.1.1) by dose level and 
schedule will be tabulated. The MTD will be determined per Protocol definition. The RP2D 
will be selected as described in 4.1.1.2. The details will be provided in the DEC Charter. 

 
 
 
 
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9.3.1.2 Secondary endpoints analysis 
9.3.1.2.1 Safety analyses 
9.3.1.2.1.1 Treatment-emergent AEs 
AEs will be presented by preferred term (PT) nested within a primary system organ class 
according to the Medical Dictionary for Regulatory Activities. A TEAE is defined as an AE 
that: 
• emerges at SOT102 treatment start or afterwards, having been absent at the time of pre-
treatment (screening), or 
• re-emerges at SOT102 treatment start or afterwards, having been present at the time of pre-
treatment (screening), or 
• worsens in severity at SOT102 treatment start or afterwards relative to the pre-treatment 
state if the AE is continuous. 
Only those AEs that were treatment-emergent will be included in the summary tables. All AEs, 
treatment-emergent or otherwise, will be presented in the patient data listings. 
The incidence of TEAEs will be reported as the number (percentage) of patients with TEAEs 
by system organ class and PT. A patient will be counted only once within a system organ class 
and PT, even if the patient experienced more than one TEAE within a particular system organ 
class and PT. The number (percentage) of patients with TEAEs will also be summarized by 
maximum severity (NCI CTCAE grades) and by relationship to SOT102, and, in Part B and 
Part D, to first-line SoC treatment (Suspected [related] and Not suspected [not related]). 
9.3.1.2.1.2 Laboratory values and vital signs 
Laboratory results will be summarized using Système International (SI) units as appropriate. 
Actual value and change from baseline will be explored using descriptive statistics. 
9.3.1.2.2 Efficacy analyses 
CT or MRI tumor assessments prior to or at the date of initiation of further-line therapy will be 
used for the evaluation of tumor response. As defined by RECIST 1.1, skin lesions greater than 
1 cm may be used for disease evaluation. 
All analyses will be descriptive. The evaluation of CLDN18.2 expression status and 
gastrectomy status (gastric/GEJ adenocarcinoma only) will be taken into account. The change 
from baseline in overall tumor burden will be described for individual patients. The tumor 
responses will be tabulated. 
9.3.2 
Part C (SOT102 monotherapy, cohort expansion) 
9.3.2.1 Primary endpoint analysis 
9.3.2.1.1.1 Objective response rate 
The ORR will be defined as the number of complete responses and partial responses from all 
evaluable best overall responses (BORs). ORR will be analyzed descriptively by counts and 
percentages, together with 95% Wald CIs. 

 
 
 
 
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The BOR will be evaluated from the first post-baseline tumor assessment until progression or 
death of patient. Complete and partial response must be confirmed by a subsequent scan, 4 
weeks later at the earliest. Stable disease must last at least 6 weeks since the baseline scan; if 
not, at least one follow-up scan is required to declare stable disease. 
9.3.2.2 Secondary endpoints analysis 
9.3.2.2.1 Safety analyses 
9.3.2.2.1.1 Treatment-emergent AEs 
The analysis of TEAEs will follow the definitions of the analyses for this endpoint in Part A 
and Part B. 
9.3.2.2.1.2 Laboratory values and vital signs 
Laboratory results will be summarized using SI units as appropriate. Actual value and change 
from baseline will be explored using descriptive statistics. 
9.3.2.2.2 Efficacy analyses 
Only CT or MRI tumor assessments prior to or at the date of initiation of further-line therapy 
will be used for the evaluation of tumor response. 
9.3.2.2.2.1 Duration of response 
The DoR will be defined as time from the first achieved response (complete or partial, 
confirmed) until the first date of radiological progression or death. 
Patients with missing data will be censored/considered as having an event as specified below: 
Situation 
Date of event or censoring 
Outcome 
No progression, no death. No start 
of new anticancer therapy. 
Date of the last evaluable tumor 
assessment. 
Censored 
No progression, no death. Start of 
new anticancer therapy. 
Date of the last tumor assessment with 
non-progression before the start of new 
anticancer therapy. 
Censored 
Progression or death after one 
missed adequate tumor assessment. 
Date of progression or death, whichever 
is earliest (if both occur). 
Event 
Progression or death after more 
than one missed adequate tumor 
assessments. 
Date of the last evaluable tumor 
assessment. 
Censored 
The DoR will be summarized using a standard set of summary statistics for time-to-event data. 

 
 
 
 
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9.3.2.2.2.2 Progression-free survival 
PFS will be defined as the time from trial enrollment until the first date of radiological 
progression or death. 
Patients with missing data will be censored/considered as having an event as specified below: 
Situation 
Date of event or censoring 
Outcome 
Incomplete or no baseline tumor 
assessment. 
Eligibility. 
Censored 
Start of new anticancer therapy. 
Date of the last tumor assessment with 
non-progression before the start of new 
anticancer therapy. 
Censored 
Death before the first disease 
progression assessment. 
Date of death. 
Event 
Death between adequate tumor 
assessment visits. 
Date of death. 
Event 
Progression or death after one 
missed adequate tumor assessment. 
Date of progression or death, whichever 
is earliest (if both occur). 
Event 
Progression or death after more 
than one missed adequate tumor 
assessments. 
 
Date of the last evaluable tumor 
assessment. 
Censored 
No progression, no death. 
Date of the last evaluable tumor 
assessment. 
Censored 
PFS will be summarized using a standard set of summary statistics for time-to-event data. 
9.3.2.2.2.3 Overall survival 
OS will be defined as the time from eligibility verification until the date of death. Patients who 
do not die will be censored at the date the patient was last known to be alive. 
OS will be summarized using a standard set of summary statistics for time-to-event data. 
9.3.2.2.2.4 Clinical benefit rate 
Clinical benefit rate will be defined as the number of complete responses, partial responses, 
and stable diseases from all evaluable BORs. 
Clinical benefit rate will be summarized by counts and percentages, along with 95% Wald CIs. 
9.3.3 
Part D (SOT102 combined with first-line SoC treatment, cohort expansion) 
Part D primary and secondary analyses will follow the definitions of Part C analyses. 

 
 
 
 
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9.4 Interim analysis 
No interim analyses are planned in this trial. 
9.5 Sample size determination 
9.5.1 
Part A (SOT102 monotherapy, dose escalation) 
A 3+3 design dose escalation will be applied until the MTD is identified. Therefore,  
3 to 6 DLT-evaluable patients per dose level will be included. Assuming 26 patients have been 
enrolled prior to this Protocol Amendment and expected enrollment upon trial restart of 
additional three patients at dose level 2, followed by two dose levels per 6 patients and 
additional patients for confirmation of the RP2D (acknowledging that at least 6 DLT-evaluable 
patients will be included to assess the RP2D before the respective expansion Part C is initiated), 
the total number of assumed evaluable patients is 47. Assuming 8 patients needed for 
replacement, the estimated number of patients is 55. 
9.5.2 
Part B (SOT102 combined with first-line SoC treatment, dose escalation) 
A 3+3 design dose escalation will be applied until the MTD is identified. Therefore,  
3 to 6 DLT-evaluable patients per dose level will be included. Assuming 5 patients have been 
enrolled prior to this Protocol Amendment and expected enrollment upon trial restart (only 
pancreatic cohort) of one dose level per three patients, two dose levels per 6 patients and 
additional patients for confirmation of the RP2D (acknowledging that at least 6 DLT-evaluable 
patients will be included to assess the RP2D before the respective expansion parts D is 
initiated), the total number of assumed patients is 26. Assuming 6 patients needed for 
replacement, the estimated number of patients per cohort is 32. 
9.5.3 
Part C (SOT102 monotherapy, cohort expansion) and Part D (SOT102 
combination with first-line SoC treatment, cohort expansion) 
Part C and Part D are planned to describe the efficacy and safety of SOT102 as monotherapy 
and in combination with first-line SoC treatment. No statistical testing is planned, only 
descriptive analyses will be performed. Forty patients in each part and in each indication should 
provide an adequate number of patients for preliminary efficacy exploration and safety 
assessment. 
 
 

 
 
 
 
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10 SUPPORTING 
DOCUMENTATION 
AND 
OPERATIONAL 
CONSIDERATIONS 
10.1 Appendix 1: Regulatory, ethical, and trial oversight considerations 
10.1.1 Regulatory and ethical considerations 
The Protocol, ICF, and appropriate related documents must be reviewed and approved by an 
IRB/IEC (in the US)/EC (in the EU)/equivalent committees (outside the US and EU) 
constituted and functioning in accordance with ICH Guideline E6 Good Clinical Practice 
(GCP)33 and any local regulations, and by the competent authority (CA). Any Protocol 
Amendment or revision to the ICF will be resubmitted to the IRB/IEC (in the US)/EC (in the 
EU)/equivalent committees (outside the US and EU) constituted and to the CA for review and 
approval, except for changes involving only logistical or administrative aspects of the trial (e.g., 
change of CRAs, change of telephone numbers). Documentation of IRB/IEC (in the US)/EC 
(in the EU)/equivalent committees (outside the US and EU) constituted compliance with ICH 
E6 and any local regulations regarding constitution and review conduct will be provided to the 
sponsor. 
A signed letter of trial approval from the IRB/IEC (in the US)/EC (in the EU)/equivalent 
committees (outside the US and EU) constituted must be sent to the principal investigator or, 
if regionally required, the head of the medical institution with a copy to the sponsor before trial 
start and the release of trial interventions to the site by the sponsor or its designee. If the 
IRB/IEC (in the US)/EC (in the EU)/equivalent committees (outside the US and EU) 
constituted decides to suspend or terminate the trial, the investigator (or if regionally required, 
the head of the medical institution) will immediately send the notice of trial suspension or 
termination by the IRB/IEC (in the US)/EC (in the EU)/equivalent committees (outside the US 
and EU) constituted to the sponsor. 
Trial progress is to be reported to IRBs/IECs (in the US)/ECs (in the EU)/equivalent 
committees (outside the US and EU) constituted and to CAs annually (or as required) by the 
investigator or sponsor, depending on local regulatory obligations. If the investigator is 
required to report to the IRB/IEC (in the US)/EC (in the EU)/equivalent committees (outside 
the US and EU) constituted, s/he will forward a copy to the sponsor at the time of each periodic 
report. 
The investigator(s) or the sponsor will submit, depending on local regulations, periodic reports 
and inform the IRB/IEC (in the US)/EC (in the EU)/equivalent committees (outside the US and 
EU) constituted (or if regionally required, the investigator and the relevant IRB/IEC (in the 
US)/EC (in the EU)/equivalent committees (outside the US and EU) constituted via the head 
of the medical institution) and the CA of any reportable AEs per ICH guidelines and local 
IRB/IEC (in the US)/EC (in the EU)/equivalent committees (outside the US and EU) 
constituted standards of practice. Upon completion of the trial, the investigator or sponsor will 
provide the IRBs/IECs (in the US)/ECs (in the EU)/equivalent committees (outside the US and 
EU) constituted and the CAs with a brief report of the outcome of the trial, if required. 
At the end of the trial, the sponsor will notify the IRBs/IECs (in the US)/ECs (in the 
EU)/equivalent committees (outside the US and EU) constituted and CAs as regionally 
required. 

 
 
 
 
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This trial will be conducted in accordance with standard operating procedures of the sponsor 
(or designee), which are designed to ensure adherence to applicable regulatory requirements, 
and in accordance with the current version of the Declaration of Helsinki and ICH guidelines 
on GCP. 
10.1.2 Financial disclosure 
Information on potential financial interests will be provided by all participating investigators. 
This information will be collected by the sponsor (or a delegated party) before the initiation of 
the clinical trial, during the course of the clinical trial whenever the financial interests may 
change, and for a period of one year after the completion of the clinical trial, or termination of 
a particular individual’s participation in this trial. 
10.1.3 Informed consent process 
Written informed consent will be given by each patient before any procedure of this clinical 
trial is performed. The process of obtaining the informed consent must comply with applicable 
ICH GCP E6 guidelines as implemented in EU guidelines and national regulatory 
requirements. 
It is the responsibility of the investigator that patients are clearly and fully informed about the 
purpose of the clinical trial, its potential risks and benefits, and other critical issues regarding 
the clinical trial, in which the patient volunteers to participate, before undergoing any clinical 
trial-specific procedure. 
The IRB/IEC (in the US)/EC (in the EU)/equivalent committees (outside the US and EU) 
constituted-approved written ICF, which complies with the above-mentioned regulations, will 
be provided to each patient. The patient should be given ample time to read and to understand 
the ICF, and to get the answers to any inquiry related to the clinical trial they may have. The 
ICF must be signed personally by the patient or their legally acceptable representative, and 
subsequently by the delegated investigator who obtains the consent. The patient will be 
provided with a fully signed ICF printout, and with any other written information, before their 
participation in the clinical trial. 
The process of obtaining informed consent must be documented in the patient’s source 
documents. 
The sponsor will provide the investigator with a master ICF that complies with ICH GCP 
guidelines and regulatory requirements and is considered appropriate for this clinical trial. Any 
changes to this master ICF suggested by the investigator must be agreed to by the sponsor 
before being submitted to the IRB/IEC (in the US)/EC (in the EU)/equivalent committees 
(outside the US and EU) constituted. A copy of the approved version, together with all 
accompanying approvals, must be provided to the sponsor. 
The ICF and any other information provided to patients are subject to changes and revisions 
whenever important new information relevant to patients’ willingness to continue participation 
in the clinical trial becomes available. Once the IRB/IEC (in the US)/EC (in the EU)/equivalent 
committees (outside the US and EU) constituted approval/favorable opinion on this new 
information is obtained, the delegated investigator should inform each patient about this newly 
emerging information as soon as possible. All procedures and regulations to be followed and 
mentioned above apply also to this scenario, and this process must also be documented in the 
patient’s source documents. 

 
 
 
 
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10.1.4 Data protection 
In order to ensure that personal information of each patient is kept confidential and protected, 
names and any other information that allow direct identification of a patient will not be in the 
eCRFs or included in any records or samples provided to the sponsor or sponsor’s authorized 
representatives; such information will be pseudonymized, i.e., all such information will be 
replaced by a specific code (patient number) assigned by the sponsor and all patients will be 
identified in eCRFs or any other records or samples by a patient number only. 
The personal information collected for the purposes of this trial will be held by the trial sites, 
the sponsor and sponsor’s authorized representatives, which together are responsible for 
processing of personal information in accordance with the General Data Protection Regulation 
(EU) 2016/679 and any corresponding local legislation. 
The sponsor and its authorized representatives will analyze and use the personal information 
they receive for the purposes of this trial only. These include: 
• checking patients’ suitability to take part in the trial, 
• monitoring patients’ health during treatment with SOT102 as monotherapy and in 
combination with first-line SoC treatment, 
• comparing and pooling trial results, 
• establishing whether SOT102 as monotherapy and in combination with first-line SoC 
treatment meets the appropriate standards of safety set by the authorities, 
• establishing whether SOT102 as monotherapy and in combination with first-line SoC 
treatment is effective, 
• supporting the clinical development of SOT102 as monotherapy and in combination with 
first-line SoC treatment, 
• supporting the licensing application for regulatory approval of SOT102 as monotherapy 
and in combination with first-line SoC treatment anywhere in the world, 
• supporting the marketing, distribution, sale, and use of SOT102 as monotherapy and in 
combination with first-line SoC treatment anywhere in the world, 
• complying with specific regulations governing clinical trials. 
Participation of patients in this trial is voluntary and they may withdraw from the trial at any 
time by informing the investigator. Their participation in the trial will then end and the trial 
personnel will stop collecting personal information from the patients, but the sponsor will need 
to retain and use the pseudonymized personal information and associated research results that 
have already been collected from the patient. The sponsor must do this to comply with its legal 
and regulatory obligations, to maintain the scientific integrity of the trial, and to complete the 
marketing authorization process for SOT102 as monotherapy and in combination with first-
line SoC treatment. It may be necessary to retain certain aspects of pseudonymized (coded) 
personal information for at least 25 years following the end of the trial to comply with 
applicable laws and regulatory requirements and to ensure the scientific integrity of the trial. 
If necessary for the trial purposes mentioned above, the sponsor may communicate such 
pseudonymized personal information to third parties (such as service providers, contractors, 
and research institutions that support the trial) and regulatory or other governmental agencies 
that need to check the results of the trial. 

 
 
 
 
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These third parties may be located in countries of the European Economic Area (EEA), in the 
US, and in other countries that are outside of the EEA. Some non-EEA countries may not offer 
the same level of privacy protection. However, the sponsor will keep personal information it 
receives as confidential as possible within the limits of the law. The sponsor will implement 
appropriate contractual measures, including the standard data protection contractual clauses, to 
ensure that the relevant recipients outside the EEA provide an adequate level of protection to 
personal information as set out in this form and as required by applicable law. 
The sponsor, either alone or together with other researchers, may publish or present the results 
of the trial; however, personal information will not be disclosed in any publication or 
presentation. 
All persons have certain rights to gain access to and correct any inaccuracies in the personal 
information held about them. In certain circumstances, they can also request restriction of 
processing of their personal information, object to certain types of processing of their personal 
information, request their personal information be erased and have their personal information 
provided to them or a third party in a digital format. The sponsor shall comply with the above 
requests to the fullest extent consistent with other legal and regulatory obligations and where 
required by law. 
Personal data cannot be erased, even after patients finish or terminate their participation in the 
trial, in order to guarantee the validity of the clinical research and to comply with statutory 
duties and drug authorization requirements. 
Representatives from government agencies, the local EC and sponsor or its authorized 
representatives may also need access to medical records and trial records for the purpose of 
checking data collected for the trial. 
The sponsor shall process all personal information of the patients in the trial in accordance with 
the General Data Protection Regulation (EU) 2016/679, any applicable local legislation and the 
internal data protection policies reflecting organizational and technical arrangements to avoid 
unauthorized access, disclosure, dissemination, alteration, or loss of information and personal 
data processed. The organizational and technical measures introduced by the sponsor in relation 
to a protection of personal information of the patients involve the above-mentioned 
pseudonymization of personal information, appropriate controls to restrict its employees access 
to the personal information, a physical access control to any premises where the personal 
information is stored, an electronic access and system control logging for any systems 
containing personal information, data entry and data transfer control, availability control (back-
up and recovery concept), network protection including firewalls and penetration testing 
procedures for regular testing, industry-standard security policies and procedures including 
assessment and evaluation of processes and regular training procedures. In the event of any 
security breach, the incident management procedures would be implemented, and the sponsor 
would notify such breach as applicable. 
10.1.5 Organizational structure of the trial 
The sponsor of the clinical trial, SOTIO Biotech a.s, may delegate certain tasks to designees, 
e.g., a contract research organization (CRO) or other third-party vendors. A list of such 
designated collaborators, including their contact details, will be documented in the 
investigator’s manuals/Investigator Site File. 

 
 
 
 
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10.1.6 Dissemination of clinical trial data 
By signing the Protocol (INVESTIGATOR’S DECLARATION), every participating 
investigator agrees to keep all information and results concerning the clinical trial and the 
investigational product strictly confidential. The confidentiality obligation also applies to all 
personnel involved at the investigational site. 
10.1.7 Risk management and quality assurance 
10.1.7.1 Data quality assurance 
An eCRF is required and must be completed for each patient by qualified and authorized 
personnel. All data in the eCRF must reflect the corresponding source document. Any 
correction to entries made in the eCRF must be documented in a valid audit trail where the 
correction is dated, the individual making the correction is identified, the reason for the change 
is stated, and the original data are not obscured. Only data required by the Protocol for the 
purposes of the trial should be collected. The investigator must sign the eCRFs. 
10.1.8 Trial monitoring, access to source documentation, and data retention 
Before trial initiation, at the investigators’ meeting or during the Site initiation visit, a 
representative of the sponsor or a CRO will review the Protocol and eCRFs with the site staff. 
During the clinical trial, delegated CRA will oversee the progress of the clinical trial and will 
visit the site regularly to verify the completeness of patient records, reliability and accuracy of 
entries in eCRFs, the site’s adherence to the Protocol and GCP, the progress of enrollment, and 
that trial interventions are being stored, dispensed, and accounted for according to 
specifications. The CRA will also verify that the safety and rights of the patients are not 
compromised. Key clinical trial personnel must be available to assist the CRA during these 
visits. 
For each patient recruited into the clinical trial, the investigator must maintain source 
documents, which should consist of case and visit notes (hospital or outpatient clinic medical 
records) containing demographic and medical information, laboratory data, and results of any 
other tests or assessments. All information in eCRFs must be traceable to these source 
documents in the patient’s file. The investigator must also keep the original of the ICF signed 
by the patient or their legally acceptable representative (the second signed original must be 
given to the patient). 
The investigator must allow the CRAs or other delegated representatives to visit all site 
locations, and to allow direct access to all clinical trial-related documentation and data, as well 
as to the patient’s source documents and other charts and records. 
Monitoring standards of the sponsor require full verification for the presence of a fully signed 
and dated ICF, adherence to the inclusion/exclusion criteria, documentation of SAEs, and 
recording of data that will be used for all primary and safety variables. Additional verification 
of the consistency of the source data with the eCRFs will be performed according to a clinical 
trial-specific Monitoring Plan. 
Monitoring details describing strategy (e.g., risk-based initiatives in operations and quality 
such as risk management and mitigation strategies and analytical risk-based monitoring), 
methods, responsibilities and requirements, including handling of non-compliance issues and 
monitoring techniques (central, remote, or on-site monitoring) are provided in the Monitoring 
Plan. 

 
 
 
 
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The sponsor assumes accountability for actions delegated to other individuals (e.g., CROs). 
The trial may also be evaluated by any other designee delegated by the sponsor, IRB/IEC (in 
the US)/EC (in the EU)/equivalent committees (outside the US and EU) constituted 
representatives, or by any independent institutional or government inspectors, who must be 
given direct access to the same as mentioned above. Such a possibility must also be clearly 
mentioned in the patient’s ICF. 
The investigator must promptly notify the sponsor or its delegated representatives any time the 
request for inspection is raised by any regulatory agency, and provide copies of all 
documentation received from such an agency. 
The investigator or institution must retain all trial-related records, materials provided by the 
sponsor or its delegated collaborators, copies of eCRFs, and source documents of patients for 
a specified period of time. This period of time is derived from the locally applicable regulation 
guidelines or requirements, institution procedures, or requirements stipulated by the sponsor or 
its representatives, whichever is longer. 
It is requested that at the completion of the required retention period, or should the investigator 
retire or relocate, the investigator must contact the sponsor, allowing the sponsor the option of 
permanently retaining the trial records. 
10.1.9 Publication policy 
The results of this clinical trial will be published and/or presented at scientific meetings in their 
totality in a timely manner. No single institution presentation/publication of data is foreseen if 
not agreed by the sponsor and all relevant investigators of the trial. Any formal publication of 
clinical trial results will be a collaborative effort between the sponsor and the investigator(s). 
All manuscripts or abstracts will be reviewed and approved in written by the sponsor before 
submission. The sponsor may request a delay in publication if there are important intellectual 
property concerns but does not have the right to suppress the publication of the clinical trial 
results indefinitely. 
Authorship will be determined by mutual agreement, with the coordinating investigator of this 
clinical trial being given priority for first authorship. Publications will include all clinical trial 
investigators in the order of their relative patient contribution, taking into account also 
contributions during Protocol development and data analyses. 
10.1.10 Committees 
10.1.10.1 
Independent committees 
10.1.10.1.1 
Data monitoring committee 
An IDMC will be established for trial Part C and Part D to safeguard the interest and safety of 
the patients participating in the trial. The IDMC will provide independent review and 
assessment of the interim efficacy and safety results on a regular basis in a systematic manner. 
The efficacy data will include descriptive analysis as described in the IDMC Charter. 
The membership, key responsibilities of the IDMC, and corresponding procedures will be 
defined in the IDMC Charter. 

 
 
 
 
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10.1.11 Future research 
Biological samples collected during this trial may be stored for future research by the sponsor. 
Storage conditions will be in compliance with the standards for repositories of biological 
samples, according to the “Recommendation CM/Rec (2016)6 of the Committee of Ministers 
to member States on research on biological materials of human origin”.34 
The repository will have independent monitoring that will guarantee protection of the data and 
the patients’ interests (also see section 10.1.4). Except for contractors of the sponsor, the 
samples will not be transferred to third parties, and they will not be sold to third parties. The 
exploratory studies that will be conducted with the samples will undergo a rigorous 
independent review evaluating both ethical and scientific aspects. 
10.2 Appendix 2: Hy’s law 
Drugs are likely to cause a high rate (10-50%) of fatal liver injury or need for transplant in 
patients with acute hepatocellular injury sufficient to cause jaundice. Hy’s law is a rule of 
thumb that a patient is at high risk of a fatal drug-induced liver injury if given a medication that 
causes hepatocellular injury (not cholestatic injury) with jaundice. 
Hy’s law cases have three components: 
• The drug causes hepatocellular injury, generally defined as an elevated ALT or AST by  
3-fold or greater above the ULN. Often with aminotransferases much greater (5-10×ULN). 
• Among patients showing such aminotransferase elevations, they also have elevation of their 
serum total bilirubin of greater than 2×ULN, without findings of cholestasis (defined as 
serum alkaline phosphatase (ALP) activity less than 2×ULN). 
No other reason can be found to explain the combination of increased aminotransferase and 
serum total bilirubin, such as viral hepatitis, alcohol abuse, ischemia, preexisting liver disease, 
or another drug capable of causing the observed injury. 
10.3 Appendix 3: Cockcroft-Gault formula 
For males, creatinine clearance is estimated using the Cockcroft-Gault formula as follows: 
Creatinine clearance = [(140 − age) × weight]/(72 × serum creatinine) 
Where age is in years, weight is in kilograms, and serum creatinine is in mg/dL. Actual, not 
ideal weight is to be used. 
For females, creatinine clearance is estimated by multiplying the result of the above formula 
by 0.85. 
10.4 Appendix 4: Laboratory parameters to be assessed 
10.4.1 Coagulation 
Coagulation tests will include prothrombin time and INR. 
10.4.2 Hematology 
• Leukocytes 
• Erythrocytes 
• Hemoglobin 

 
 
 
 
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• Hematocrit 
• Platelets 
• Differential: 
o Neutrophils 
o Lymphocytes 
o Monocytes 
o Eosinophils 
o Basophils 
Treatment decisions will be based on local laboratory results. 
10.4.3 Clinical chemistry 
• ALT 
• Albumin, serum albumin* 
• ALP 
• Amylase 
• AST 
• Bilirubin 
• Blood urea nitrogen or blood urea 
• Calcium 
• Creatinine 
• Glucose (fasting) 
• Lactate dehydrogenase 
• Lipase 
• Magnesium 
• Potassium 
• Serology (HIV, HBV-positive patients only) 
• Sodium 
• TSH (for Part B gastric only) 
• Urea* 
* Parameters to be measured on D8 of each cycle 
Note: For country-specific requirements, see section 10.8. 
10.4.4 Urinalysis 
• Leukocytes 
• Blood 
• Glucose 
• Ketones 
• pH 
• Protein 

 
 
 
 
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• Specific gravity 
• Urine leukocyte esterase 
 
Urine analysis must be performed in a laboratory. Urine dipstick test alone is not allowed. Entry 
limit at screening is grade 1 proteinuria (<1 g/24 hours; see section 5.1.1). Urinalysis will be 
performed prior to each day 1 of each cycle and in case of detection of ≥100 mg/dL proteinuria, 
a 24-hour urine analysis will have to be performed (prior to the start of SOT102 treatment) to 
document 24-hour proteinuria levels. 

 
 
 
 
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10.5 Appendix 5: List of medications requiring special caution 
Medications that may prolong the QT interval are:35 
Known risk 
Conditional risk 
Possible risk 
Amiodarone 
Amantadine 
Alfuzosin 
Azithromycin 
Amisulpride 
Aripiprazole 
Chlorpromazine 
Amitriptyline 
Asenapine 
Ciprofloxacin 
Fluoxetine 
Atazanavir 
Citalopram 
Furosemide 
Clomipramine 
Domperidone 
Hydrochlorothiazide 
Clozapine 
Donepezil 
Hydroxychloroquine 
Imipramine 
Escitalopram 
Indapamide 
Lithium 
Fluconazole 
Ivabradine 
Mirtazapine 
Haloperidol 
Metoclopramide 
Nortriptyline 
Levofloxacin 
Pantoprazole 
Olanzapine 
Levomepromazine 
Paroxetine 
Paliperidone 
Methadone 
Quetiapine 
Rilpivirine 
Ondansetron 
Ritonavir 
Risperidone 
Sulpiride 
Sertraline 
Saquinavir 
 
Trazodone 
Tamoxifen 
 
Ziprasidone 
Tetrabenazine 
 
 
Trimipramine 
 
 
Venlafaxine 
Medications that may induce CYP2C8, CYP2C9, and/or CYP3A4/CYP3A are:36 
Cytochrome 
Strong induction 
Moderate induction 
Weak induction 
CYP2C8 
 
Rifampin 
 
CYP2C9 
 
Enzalutamide 
Apalutamide 
 
 
Rifampin 
Aprepitant 
 
 
 
Carbamazepine 
 
 
 
Ritonavir 
CYP3A 
Apalutamide 
Bosentan 
Armodafinil 
 
Carbamazepine 
Efavirenz 
Modafinil 
 
Enzalutamide 
Etravirine 
Rufinamide 
 
Mitotane 
Phenobarbital 
 

 
 
 
 
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Cytochrome 
Strong induction 
Moderate induction 
Weak induction 
 
Nevirapine 
Primidone 
 
 
Rifampin 
 
 
 
St. John’s wort 
 
 
Medications that may inhibit CYP2C8, CYP2C9, CYP2D6, and/or CYP3A4/CYP3A are:36 
Cytochrome 
Strong inhibition 
Moderate inhibition 
Weak inhibition 
CYP2C8 
Gemfibrozil 
Clopidogrel 
Trimethoprim 
 
 
Deferasirox 
 
 
 
Teriflunomide 
 
CYP2C9 
 
Amiodarone 
Diosmin 
 
Fluconazole 
Disulfiram 
 
Miconazole 
Fluvastatin 
 
Piperine 
Fluvoxamine 
 
 
Voriconazole 
CYP2D6 
Bupropion 
Abiraterone 
Amiodarone 
 
Fluoxetine 
Cinacalcet 
Celecoxib 
 
Paroxetine 
Duloxetine 
Cimetidine 
 
Quinidine 
Lorcaserin 
Clobazam 
 
Terbinafine 
Mirabegron 
Cobicistat 
 
 
 
Escitalopram 
 
 
 
Fluvoxamine 
 
 
 
Labetalol 
 
 
 
Ritonavir 
 
 
 
Sertraline 
 
 
 
Vemurafenib 
CYP3A4 
Boceprevir 
Aprepitant 
Chlorzoxazone 
 
Clarithromycin 
Ciprofloxacin 
Cilostazol 
 
Cobicistat 
Conivaptan 
Cimetidine 
 
Danoprevir and 
ritonavir 
Crizotinib 
Clotrimazole 
 
Elvitegravir and 
ritonavir 
Cyclosporine 
Fosaprepitant 
 
Grapefruit juice 
Diltiazem 
Istradefylline 

 
 
 
 
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Cytochrome 
Strong inhibition 
Moderate inhibition 
Weak inhibition 
 
Idelalisib 
Dronedarone 
Ivacaftor 
 
Indinavir and 
ritonavir 
Erythromycin 
Lomitapide 
 
Itraconazole 
Fluconazole 
Ranitidine 
 
Ketoconazole 
Fluvoxamine 
Ranolazine 
 
Lopinavir and 
ritonavir 
Imatinib 
Ticagrelor 
 
Nefazodone 
Tofisopam 
 
 
Nelfinavir 
Verapamil 
 
 
Paritaprevir and 
ritonavir and 
(ombitasvir and/or 
dasabuvir) 
 
 
 
Posaconazole 
 
 
 
Ritonavir 
 
 
 
Saquinavir and 
ritonavir 
 
 
 
Telaprevir 
 
 
 
Telithromycin 
 
 
 
Tipranavir and 
ritonavir 
 
 
 
Troleandomycin 
 
 
 
Voriconazole 
 
 
Medications that are substrates of CYP2D6, and/or CYP3A are:36 
Cytochrome 
Sensitive substrates 
Moderate sensitive substrates 
CYP2D6 
Atomoxetine 
Desipramine 
Dextromethorphan 
Eliglustat 
Nebivolol 
Nortriptyline 
Perphenazine 
Tolterodine 
R-venlafaxine 
Encainide 
Imipramine 
Metoprolol 
Propafenone 
Propranolol 
Tramadol 
Trimipramine 
S-venlafaxine 
CYP3A 
Alfentanil 
Avanafil 
Alprazolam 
Aprepitant 

 
 
 
 
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Cytochrome 
Sensitive substrates 
Moderate sensitive substrates 
Budesonide 
Buspirone 
Conivaptan 
Darifenacin 
Darunavir 
Dasatinib 
Dronedarone 
Ebastine 
Eletriptan 
Eplerenone 
Everolimus 
Felodipine 
Ibrutinib 
Indinavir 
Lomitapide 
Lovastatin 
Lurasidone 
Maraviroc 
Midazolam 
Naloxegol 
Nisoldipine 
Quetiapine 
Saquinavir 
Sildenafil 
Simvastatin 
Sirolimus 
Tacrolimus 
Ticagrelor 
Tipranavir 
Tolvaptan 
Triazolam 
Vardenafil 
Atorvastatin 
Colchicine 
Eliglustat 
Pimozide 
Rilpivirine 
Rivaroxaban 
Tadalafil 
 
 

 
 
 
 
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10.6 Appendix 6: Abbreviations 
Abbreviation 
Term 
5-FU 
Fluorouracil 
ADA 
Anti-drug antibody 
ADC 
Antibody-drug conjugate 
AE 
Adverse event 
AIDS 
Acquired immunodeficiency syndrome 
ALT 
Alanine transaminase  
ALP 
Alkaline phosphatase 
AST 
Aspartate transaminase 
AxMP 
Auxiliary medicinal product 
BOR 
Best overall response 
BRCA 
Breast cancer gene 
CA 
Competent authority 
CD 
Cluster of differentiation 
CI 
Confidence interval 
CLDN18.2 
Claudin 18 splice variant 2 
CRA 
Clinical research associate 
CRO 
Contract research organization 
CT 
Computed tomography 
CYP2C8 
Cytochrome P2C8 
CYP2C9 
Cytochrome P2C9 
CYP2D6 
Cytochrome P2D6 
CYP3A(4) 
Cytochrome P3A(4) 
CYP450 
Cytochrome P450 
DEC 
Dose Escalation Committee  
DEM 
Dose Escalation Meeting  
DLn 
Dose level number 
DLT 
Dose-limiting toxicity 
DNA 
Deoxyribonucleic acid 
DoR 
Duration of response  
DPD 
Dihydropyrimidine dehydrogenase  
EC 
Ethics committee  
ECG 
Electrocardiogram 
ECOG  
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
EDA 
Ethylene diamine  
EEA 
European Economic Area  
EU 
European Union 
FFPE 
Formalin-fixed paraffin-embedded  

 
 
 
 
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Abbreviation 
Term 
FOLFIRINOX 
Leucovorin calcium, fluorouracil, irinotecan hydrochloride, and 
oxaliplatin 
GCP 
Good Clinical Practice  
GEJ 
Gastroesophageal junction  
HBV 
Hepatitis B 
HCV 
Hepatitis C 
HER2 
Human epidermal growth factor receptor 2 
HIV 
Human immunodeficiency virus 
HNSTD 
Highest non-severely toxic dose 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
IDMC 
Independent data monitoring committee  
IEC 
Independent ethics committee 
ICH 
International Council for Harmonisation  
IHC 
Immunohistochemistry 
INR 
International normalized ratio 
IRB 
Institutional review board  
IV 
Intravenous 
LVEF 
Left ventricular ejection fraction  
mFOLFOX6 
Modified oxaliplatin + leucovorin + 5-fluorouracil-containing 
chemotherapy regimen 
MRI 
Magnetic resonance imaging 
MTD 
Maximum tolerated dose  
MUGA 
Multiple gated acquisition scanning 
Nab-paclitaxel 
Paclitaxel protein-bound 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse 
Events  
ORR 
Objective response rate  
OS 
Overall survival 
PFS 
Progression-free survival  
PK 
Pharmacokinetics 
PT 
Preferred term 
QoL 
Quality of life 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
Recommended phase 2 dose  
SAE 
Serious adverse event 
SaO2 
Arterial oxygen saturation 
SI 
Système International 
SmPC 
Summary of Product Characteristics 

 
 
 
 
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Abbreviation 
Term 
SoC 
Standard of care 
SOT102 
CLDN18.2-specific monoclonal antibody SOT102.1 conjugated to 
 
STD10 
Severely toxic dose in 10% of the animals 
SUSAR 
Suspected unexpected serious adverse reaction 
TEAE 
Treatment-emergent adverse event 
ULN 
Upper limits of normal  
US 
United States of America 
WOCBP 
Woman of childbearing potential 
*Abbreviations of commonly used weight, height, and volume measures are not listed above. 

 
 
 
 
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10.7 Appendix 7: Protocol Amendment history 
The PROTOCOL AMENDMENT SUMMARY OF CHANGES for the current amendment is located directly before the TABLE OF CONTENTS. 
10.7.1 Amendment 4 (08Mar2024): Protocol changes implemented 
Change 
number 
Description of change  
Rationale for change 
Section in Amendment 4 
1 
The population of the trial was changed to include only 
patients with pancreatic cancer in the future. Gastric/GEJ 
cohorts were removed from parts C and D. Relevant 
information was modified throughout the document. 
Sample size was updated accordingly. 
 
For patients ongoing in gastric cohort, notes specifying 
time windows for some assessments have been updated to 
reflect that no SOT102 will be administered. 
Enrollment of patients with gastric/GEJ 
cancer was stopped by the decision of the 
sponsor. Due to gastric/GEJ patients being 
enrolled and continuing in Part B at the time 
of the Protocol update, relevant information 
has been kept in the Protocol. 
 
SOT102 will not be administered to patients 
anymore, some assessments do not need to 
be made or do not need to be made within a 
related time window. 
Throughout the document; 1.3.2 Schedule of 
activities Part B gastric; 
2 
Introduction of premedication with corticosteroids a day 
before, on the day of (at least 1 hour prior), and the day 
after SOT102 administration 
To reflect renal toxicity safety signals, and to 
prevent and/or ameliorate any inflammatory 
stimulation of podocytes 
1.1 Synopsis; 1.3.1, Schedule of activities Part A; 
1.3.3 Schedule of activities Part B pancreatic; 1.3.4 
Schedule of activities Part C;1.3.5 Schedule of 
activities Part D pancreatic; 6.1.1 SOT102 (all trial 
parts); 
3 
Assessment of clinical chemistry with focus on renal 
function, urinalysis and creatinine clearance added on day 
8 of each cycle in parts A and B. Urine spot analysis 
added before SOT102 administration and every day 8 of 
each cycle in parts A and B. Assessment of clinical 
chemistry, urinalysis, and creatinine clearance added on 
day 21 in Part B. 
To monitor renal function of patients more 
closely 
1.3.1, Schedule of activities Part A; 1.3.3 Schedule 
of activities Part B pancreatic; 10.4.3 Clinical 
chemistry; 10.4.4 Urinalysis 
4 
For LVEF and tumor assessments: assessments obtained 
prior the ICF signature as a part or standard of 
care/routine practice may be used for screening and trial 
purposes 
To allow use of earlier assessments for the 
purpose of the trial 
1.3.1, Schedule of activities Part A; 1.3.2 Schedule 
of activities Part B gastric; 1.3.3 Schedule of 
activities Part B pancreatic; 1.3.4 Schedule of 
activities Part C; 1.3.5 Schedule of activities Part D 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment 4 
gastric; 1.3.6 Schedule of activities Part D 
pancreatic 
5 
Clarification added that urine dipstick cannot be used for 
assessment of urinalysis 
To inform investigators not to use qualitative 
assessments of urinalysis. 
1.3.1, Schedule of activities Part A; 1.3.2 Schedule 
of activities Part B gastric; 1.3.3 Schedule of 
activities Part B pancreatic; 1.3.4 Schedule of 
activities Part C; 1.3.5 Schedule of activities Part D 
gastric; 1.3.6 Schedule of activities Part D 
pancreatic; 10.4.4 Urinalysis 
6 
Addition of a 2-hour window for ECG at 24 hours after 
the end of SOT102 infusion in cycles 1 and 3 
To add time allowance for measurement of 
ECG after drug administration 
1.3.1, Schedule of activities Part A; 1.3.2 Schedule 
of activities Part B gastric; 1.3.3 Schedule of 
activities Part B pancreatic; 8.2.4 
Electrocardiography 
7 
Esophagogastroduodenoscopy at screening is to be done 
up to 6 months before cycle 1 day 1 in parts C and D 
To clarify screening/eligibility conditions 
1.3.4 Schedule of activities Part C; 1.3.5 Schedule 
of activities Part D gastric; 1.3.6 Schedule of 
activities Part D pancreatic 
8 
Addition of PK samples to be collected at occurrence of 
grade ≥3 AE and at the time SOT102 treatment resumes 
and at occurrence of grade 4 AE 
 
Addition of PK sample to be collected at time of disease 
progression 
 
Addition of dense PK sampling to cycle 5 of SOT102 
therapy 
To collect PK data at the time of occurrence 
of toxicity and at the time the treatment is 
resumed 
 
To allow more precise assessment of 
presence and role of ADA 
 
To obtain more precise PK data at a later 
time of SOT102 exposure 
1.3.6 PK and ADA sampling (SOT102), Part A and 
Part B; 1.3.7 PK and ADA sampling (SOT102), Part 
C and Part D 
9 
Addition of ADA sample collection at the time of disease 
progression in parts A and B 
To explore the dynamics of ADA at the time 
of disease progression and also to investigate 
if those ADAs are potentially neutralizing at 
that time 
1.3.6 PK and ADA sampling (SOT102), Part A and 
Part B 
10 
Definition of DLT-evaluable patient in Part B extended 
with information on SoC 
To include patients who also receive 
corresponding SoC treatment  
4.1.1 Dose escalation plan (Part A and Part B) 
11 
Grade ≥2 serum creatinine elevation and grade ≥2 
proteinuria added to the list of AEs considered DLTs 
To reflect renal toxicity safety signals and 
ensure safety of patients 
4.1.1.1 Dose-limiting toxicities definitions 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment 4 
12 
End of trial definition updated to include information on 
trial start. Section 10.1.8 Trial start and closure removed. 
To better define trial start 
4.4 Trial and site start and closure 
13 
Inclusion criteria on availability of tumor biopsy samples 
in sections with trial parts specifics were merged into 
criterion no. 13  
To clarify screening/eligibility conditions 
5.1.1 Inclusion criteria applicable to all trial parts; 
5.1.2 Inclusion criteria specific to Part A; 5.1.3 
Inclusion criteria specific to Part B; 5.1.4 Inclusion 
criteria specific to Part C; 5.1.5 Inclusion criteria 
specific to Part D 
14 
Exclusion criterion no. 1 on prior therapy with 
CLDN18.2-directed agents removed 
To clarify screening/eligibility conditions 
5.2.1 Exclusion criteria applicable to all trial parts 
15 
Exclusion criterion no. 19 updated to include information 
on completion of full vaccination series if feasible 
To provide more clarity to investigators 
5.2.1 Exclusion criteria applicable to all trial parts 
16 
Exclusion criterion on time since last transfusion before 
cycle 1 day 1 added to all trial parts (no. 17) and related 
restriction removed from inclusion criterion no. 3.1 
To clarify screening/eligibility conditions 
5.1.1 Inclusion criteria applicable to all trial parts; 
5.2.1 Exclusion criteria applicable to all trial parts 
17 
Clarification added to definition of screen failures that 
these are patients who fail to meet the eligibility criteria 
To provide better guidance to investigators 
5.4 Screen failures 
18 
Addition of reporting of medication errors, including 
abuse, misuse and/or over/underdose 
To comply with regulatory guidance 
6.4 Trial intervention compliance 
19 
Rules for dose modification in case of a grade ≥3 AE 
clarified 
To provide better guidance to investigators 
6.5.1 Dose modification and toxicity management of 
SOT102 
20 
Clarification on auxiliary medicinal products added 
To provide better guidance to investigators 
and to comply with regulatory guidance 
6.8.1 Rescue medication and supportive care 
21 
NSAIDs and other potentially nephrotoxic medications 
should be used with caution when administered with 
SOT102 
To provide more safety for patients 
6.8.3 Medications requiring caution 
22 
DLT conditions added to causes for discontinuation of 
trial intervention  
To provide better guidance for investigators 
7.1 Discontinuation of trial intervention 
23 
All safety assessments should be carried out according to 
standard local institutional practice unless otherwise 
stated in the Protocol 
To provide more clarity to investigators 
8.2 Safety assessments 
24 
Specific timelines for reporting SUSARs replaced with 
information on the need to follow national safety 
reporting requirements for reporting 
To provide more clarity to investigators 
8.3.5 Regulatory reporting requirements for SAEs 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment 4 
25 
Restrictions for egg and sperm donations after SOT102 
treatment added 
To provide more safety for patients 
8.3.6 Pregnancy 
26 
Addition of clarification on AE causality assessment 
To provide better guidance for investigators 
8.3.7.1 Causality 
27 
Section on tumor biopsy added  
To provide more clarity to investigators 
8.6 Tumor biopsy 
28 
Clarification added that skin lesions may be used for 
disease evaluation as defined by RECIST 1.1 
To provide better guidance for investigators 
9.3.1.2.2 Efficacy analyses 
29 
Reporting of neutrophils by automated differential 
instruments and the final count including segmented and 
band forms removed 
To provide more clarity to investigators 
10.4.2 Hematology 
30 
EudraCT number updated to EUCT number, NCT 
number added 
To update regulatory identifiers 
Title page; 1.1 Synopsis 
31 
Change of sponsor address 
Administrative change 
Title page 
32 
Overview of Objectives and Endpoints was converted to 
a table 
For better clarity 
3 Objectives and Endpoints 
33 
Update of contact information or reporting of 
SAEs/pregnancies. Removal of fax/telephone number for 
reporting SAEs/pregnancies. 
Administrative change 
8.3.8.3 Immediately reportable events 
34 
Minor wording and punctuation corrections 
To align Protocol with new regulatory 
guidance and to improve clarity and 
readability  
Throughout the document 
10.7.2 Amendment 3 (27Apr2023): Protocol changes implemented 
Change 
number 
Description of change  
Rationale for change 
Section in Amendment 3 
1 
Trial Protocol synopsis adjusted to follow the CTR 
recommended order of information 
To align format of synopsis with global 
recommendations (no content change, only 
updated order of information and addition of 
Ethical considerations) 
1.1 Synopsis 
2 
A correction was made to the Schedule of activities for 
Part D pancreatic – body weight is to be collected on 
D15, not D21 
To correct an error 
1.3.6 Schedule of activities, Part D pancreatic 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment 3 
3 
Inclusion criterion no. 12 harmonized between global 
Amendment 2 (01Sep2022) and local amendment FR-3 
(01Sep2022) 
To include French local specificity requested 
by ANSM into one consolidated Protocol 
5.1.1 Inclusion criteria applicable to all trial parts; 
10.8 Appendix 8: Country-specific 
requirements/differences 
4 
Information on country-specific set of laboratory tests to 
be made was added 
To include French local specificity requested 
by ANSM into one consolidated Protocol 
10.4.3 Clinical chemistry; 10.8 Appendix 8: 
Country-specific requirements/differences 
5 
Adding the possibility of having the trial assessed by 
committee equivalent to IRB/IEC/EC (outside the US and 
EU) 
To allow the trial to be conducted outside of 
US/EU 
Throughout the document 
6 
Minor wording and punctuation corrections 
To improve clarity and readability  
Throughout the document 
10.7.3 Amendment FR-3 (01Sep2022): Protocol changes implemented 
Change 
number 
Description of change  
Rationale for change 
Section in Amendment FR-3 
1 
Objectives and endpoints were updated to include 
additional analytes in PK analyses 
To better characterize the PK of the trial drug 
1.1 Synopsis ; 3.1.1 – 3.1.4 Objectives (Part A, Part 
B, Part C, Part D) ; 3.2.1 – 3.2.4 Endpoints (Part A, 
Part B, Part C, Part D) 
2 
A note was modified in Schedule of activities for 
all parts to day 1 to allow a window of ±1 day 
starting from cycle 6 (note 14 for Part A and Part 
B) or cycle 2 (note 15 for Part C and Part D) for 
dosing of SOT102 and/or first-line SoC treatment; 
a window of 1 day early was added for the 
collection of safety laboratory samples starting 
from cycle 2 for all trial parts (note 16 for Part A 
and Part B, note 18 for Part C and Part D) 
To provide more operational flexibility to trial sites 
1.3.1 – 1.3.6 Schedule of activities (Part A, Part B, 
Part C, Part D); 6.5.1 Dose modification and 
toxicity management for SOT102; 6.5.2 Dose 
modification and toxicity management for first-line 
SoC treatment; 8.2.5 Clinical safety laboratory 
assessments 
3 
Schedule of collection of immunogenicity 
sampling was clarified for all trial parts 
Revised for better clarity 
1.3.1 – 1.3.6 Schedule of activities (Part A, Part B, 
Part C, Part D) 
4 
Time period and frequency for collecting 
AEs/TEAEs was clarified 
Revised for better clarity 
4.1.1.4.1 Part A; 4.1.1.4.2 Part B; 8.3.2 Time period 
and frequency for collecting AE, SAE, and other 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment FR-3 
reportable safety event information; 9.3.1.2.1.1 
Treatment-emergent AEs 
5 
Schedule of pregnancy testing during the trial was 
clarified in Part B pancreatic and Part D pancreatic 
Revised according to the AFMPS’s request/ 
recommendation (06Apr2022) 
1.3.3 Schedule of activities (Part B pancreatic), 
1.3.6 Schedule of activities (Part D pancreatic) 
6 
Schedule of physical exams, vital signs, 
biochemistry, urinalysis, creatinine clearance, and 
ECG determinations was clarified in Part B 
pancreatic and Part D pancreatic; body weight 
measurement added to day 15 
Revised according to the AFMPS’s request/ 
recommendation (06Apr2022) 
1.3.3 Schedule of activities (Part B pancreatic), 
1.3.6 Schedule of activities (Part D pancreatic) 
7 
Schedule of QoL assessments was clarified 
Revised for better clarity 
1.3.4 – 1.3.6 Schedule of activities (Part C, Part C 
gastric, Part D pancreatic; 8.1.2 Quality of life 
assessments (only in Part C and Part D) 
8 
In schedules of activities for Part A and Part B 
urine was added to PK sampling. In PK sampling 
schedule correction was made to specify that for 
urine, only concentrations will be measured. Urine 
PK sample collection timing was clarified, a note 
was added that urine PK sample collection 
schedule will be specified in the Laboratory 
Manual. 
Revised for better clarity 
1.3.1 – 1.3.3 Schedule of activities (Part A, Part B); 
1.3.7 PK and ADA sampling (SOT102), Part A and 
Part B 
9 
Discontinuation from therapy mandated for 
patients who develop toxicities qualified as DLTs 
unless they demonstrate a clear clinical benefit 
Revised according to the AFMPS’s request/ 
recommendation (06Apr2022) 
4.1.1.1 Dose-limiting toxicities definitions 
10 
Inclusion criterion 7 was modified to recommend 
sperm preservation for males 
Revised according to the AFMPS’s 
request/recommendation (06Apr2022) 
5.1.1 Inclusion criteria applicable to all trial parts 
11 
Addition of exclusion criterion no. 19 for all trial 
parts to exclude patients treated with a live or live-
attenuated vaccine 30 days before treatment 
administration; information about not allowing 
vaccination with live or live-attenuated vaccines 
Revised according to the SUKL’s recommendation 
(SUKL RFI 11Feb2022) 
5.2.1 Exclusion criteria applicable to all trial parts; 
6.8.3 Medications requiring special caution 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment FR-3 
during the trial and within 90 days after the last 
dose of SOT102 and/or SoC added 
12 
Information was added that caution should be 
exercised when administering trial medication 
with medications known as substrates of CYP2D6 
and CYP3A, when administering trial medication 
or nab-paclitaxel with QT/QTc interval-
prolonging medications; recommendation against 
use of CYP2C8 and CYP3A4 inducers added for 
EU in cohorts including nab-paclitaxel 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022), AFMPS’s 
request/recommendation (11May2022), and 
AFMPS’s request/ recommendation (06Apr2022) 
6.8.3 Medications requiring special caution; 6.8.3.2 
Nab-paclitaxel 
13 
Clarification was added of the timing of radiology 
assessments throughout the study 
Revised for better clarity 
8.1.1 Radiologic evaluation of disease 
14 
ECOG collection moved from section on efficacy 
measures (8.1.2) to section on safety (8.2.1) 
Revised for better clarity 
8.2.1 Physical examinations, body height, weight, 
and surface area, ECOG performance status 
15 
Information on what needs to be documented in 
eCRF on AE page specified (Other suspected 
cause and Other action taken are not to be 
recorded) 
Revised for better clarity 
8.3.8.2 Documenting in eCRFs 
16 
Clarification on sponsor’s contractors being 
excluded from third parties added 
Revised for better clarity 
10.1.12 Future research 
17 
List of CYP2D6 and/or CYP3A substrates 
included in list of medications requiring special 
caution 
Revised according to the AFMPS’s request/ 
recommendation (06Apr2022) 
10.5 Appendix 5: List of medications requiring 
special caution 
18 
Change of Statistician 
Change of personnel 
SIGNATURES/PROTOCOL APPROVAL AND 
RELEASE SOTIO 
19 
Minor wording and punctuation corrections 
To improve clarity and readability  
Throughout the document 

 
 
 
 
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10.7.4 Amendment 2 (01Sep2022): Protocol changes implemented 
Change 
number 
Description of change  
Rationale for change 
Section in Amendment 2 
1 
Objectives and endpoints were updated to include 
additional analytes in PK analyses 
To better characterize the PK of the trial drug 1.1 Synopsis; 3.1.1 – 3.1.4 Objectives (Part A, Part 
B, Part C, Part D); 3.2.1 – 3.2.4 Endpoints (Part A, 
Part B, Part C, Part D) 
2 
A note was added to the trial design schema to clarify the 
patient population in Part B and Part D of the trial. In 
addition, exclusion criterion 20 for Part B and Part D was 
updated to clarify the same 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) 
1.2 Schema; 5.2.3 Exclusion criteria specific to Part 
B; 5.2.5 Exclusion criteria specific to Part D 
3 
A note was modified in Schedule of activities for all parts 
to day 1 to allow a window of ±1 day starting from cycle 
6 (note 14 for Part A and Part B) or cycle 2 (note 15 for 
Part C and Part D) for dosing of SOT102 and/or first-line 
SoC treatment; a window of 1 day early was added for 
the collection of safety laboratory samples starting from 
cycle 2 for all trial parts (note 16 for Part A and Part B, 
note 18 for Part C and Part D) 
To provide more operational flexibility to 
trial sites 
1.3.1 – 1.3.6 Schedule of activities (Part A, Part B, 
Part C, Part D); 6.5.1 Dose modification and 
toxicity management for SOT102; 6.5.2 Dose 
modification and toxicity management for first-line 
SoC treatment; 8.2.5 Clinical safety laboratory 
assessments 
4 
Monitoring of SaO2 was added to the assessments to be 
performed in the trial for all trial parts and all cohorts 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) and AFMPS’s 
request/recommendation (06Apr2022) 
1.3.1 – 1.3.6 Schedule of activities (Part A, Part B, 
Part C, Part D) 
5 
Schedule of collection of immunogenicity sampling was 
clarified for all trial parts 
Revised for better clarity 
1.3.1 – 1.3.6 Schedule of activities (Part A, Part B, 
Part C, Part D) 
6 
Monitoring of HIV and HBV for HIV and/or HBV-
positive patients was added to the assessments to be 
performed in the trial for all trial parts and all cohorts 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) 
1.3.1 – 1.3.6 Schedule of activities (Part A, Part B, 
Part C, Part D); 10.4.3 Clinical chemistry 
7 
Monitoring of AEs considered as having a suspected 
causal relationship to SOT102 per the investigator’s 
judgment and monitoring of concomitant medication was 
added to the follow-up until disease progression or start 
of new anticancer therapy in Part A and Part B and the 
timelines were clarified 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) 
1.3.1 – 1.3.3 Schedule of activities (Part A, Part B); 
4.1.1.4.1 Part A; 4.1.1.4.2 Part B; 4.1.2.4 Follow-up 
period (Part A); 4.1.3.4 Follow-up period (Part B); 
8.3.2 Time period and frequency for collecting AE, 
SAE, and other reportable safety event information; 
9.3.1.2.1.1 Treatment-emergent AEs 
8 
Monitoring of LVEF schedule for Part B was aligned 
with that of Part A; monitoring of LVEF was added to the 
assessments to be performed at 30 (±5) days after the last 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) and AFMPS’s 
request/recommendation (06Apr2022) 
1.3.2 – 1.3.6 Schedule of activities (Part B, Part C, 
Part D) 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment 2 
dose of SOT102 for trial Part B, Part C, and Part D, all 
cohorts 
9 
Schedule of pregnancy testing during the trial was 
clarified in Part B pancreatic and Part D pancreatic 
Revised according to the AFMPS’s request/ 
recommendation (06Apr2022) 
1.3.3 Schedule of activities (Part B pancreatic); 
1.3.6 Schedule of activities (Part D pancreatic) 
10 
Schedule of physical exams, vital signs, biochemistry, 
urinalysis, creatinine clearance, and ECG determinations 
was clarified in Part B pancreatic and Part D pancreatic; 
body weight measurement added to day 15 
Revised according to the AFMPS’s request/ 
recommendation (06Apr2022) and for better 
clarity 
1.3.3 Schedule of activities (Part B pancreatic); 
1.3.6 Schedule of activities (Part D pancreatic) 
11 
Schedule of QoL assessments was clarified 
Revised for better clarity 
1.3.4 – 1.3.6 Schedule of activities (Part C, Part C 
gastric, Part D pancreatic; 8.1.2 Quality of life 
assessments (only in Part C and Part D) 
12 
In schedules of activities for Part A and Part B urine was 
added to PK sampling. In PK sampling schedule 
correction was made to specify that for urine, only 
concentrations will be measured. Urine PK sample 
collection timing was clarified, a note was added that 
urine PK sample collection schedule will be specified in 
the Laboratory Manual. 
Revised for better clarity 
1.3.1 – 1.3.3 Schedule of activities (Part A, Part B); 
1.3.7 PK and ADA sampling (SOT102), Part A and 
Part B 
13 
ECG measurement schedule was clarified in footnotes 5 
and 10 of the schedules of activities for Part A and Part B 
Revised according to the ANSM’s request/ 
recommendation (17Jun2022) 
1.3.1 – 1.3.3 Schedule of activities (Part A, Part B) 
14 
Number of patients to be treated at the RP2D before 
opening expansion cohorts was clarified 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) 
4.1.1 Dose escalation plan (Part A and Part B); 
4.1.1.2 Maximum tolerated dose and selection of the 
recommended phase 2 dose; 9.5.1 Part A (SOT102 
monotherapy, dose escalation); 9.5.2 Part B 
(SOT102 combined with first-line SoC treatment, 
dose escalation) 
15 
The list of exceptions from DLTs in Protocol section 
4.1.1.1 was modified to include grade 3 or higher 
amylase or lipase not associated with symptoms or 
clinical manifestations, or radiological evidence of 
pancreatitis 
Revised according to the ANSM’s request/ 
recommendation (17Jun2022) 
4.1.1.1 Dose-limiting toxicities definitions 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment 2 
16 
Discontinuation from therapy mandated for patients who 
develop toxicities qualified as DLTs unless they 
demonstrate a clear clinical benefit 
Revised according to the AFMPS’s request/ 
recommendation (06Apr2022) 
4.1.1.1 Dose-limiting toxicities definitions 
17 
Communication plan between the sponsor, the 
investigators, and the subjects in the event of emerging 
safety issues was updated  
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) 
4.1.1.6 Communication plan  
18 
Stopping rules were moved from section 4.1.1.7 to 
section 5.5 and were updated to include all trial parts and 
all cohorts. Section 4.1.1.7 was removed. 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) and AFMPS’s 
recommendation (11 May 2022) 
5.5 Criteria for temporarily delaying 
enrollment/administration of trial intervention 
19 
Inclusion criterion 3.7 on serum concentrations of 
potassium, magnesium, and calcium within normal range 
was added 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) and AFMPS’s 
request/recommendation (06Apr2022) 
5.1.1 Inclusion criteria applicable to all trial parts 
20 
Inclusion criterion 6.2 was modified to specify that a 
highly effective contraceptive method must be used 
during the treatment period and for at least 9 months after 
the last dose of SOT102 or first-line SoC treatment 
(whichever occurs later). 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) 
5.1.1 Inclusion criteria applicable to all trial parts 
21 
Inclusion criterion 7 was modified to specify that a highly 
effective contraceptive method must be used by WOCBP 
partners of male participants and also to recommend 
sperm preservation for males 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) and AFMPS’s 
request/recommendation (06Apr2022) 
5.1.1 Inclusion criteria applicable to all trial parts 
22 
Inclusion criterion 13 for Part A and Part C was moved to 
the section of criteria applicable to all trial parts (now 
criterion 12) and the wording was updated to specify that 
it refers to treatment for locally advanced 
gastric/pancreatic cancer 
Revised for better clarity 
5.1.1 Inclusion criteria applicable to all trial parts 
23 
Exclusion criteria applicable to all trial parts was 
modified to exclude patient previously treated with 
anthracyclines at the maximum cumulative dose 
(exclusion criterion 3) 
Revised according to the ANSM’s request/ 
recommendation (17Jun2022) 
5.2.1 Exclusion criteria applicable to all trial parts 
24 
Exclusion criterion 7 was updated to specify that an 
active infection must be clinically controlled before 
patient’s inclusion in the trial 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) 
5.2.1 Exclusion criteria applicable to all trial parts 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment 2 
25 
Exclusion criterion 11 was updated to specify that 
patients with NYHA ≥2 heart failure must be excluded 
from the trial 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) 
5.2.1 Exclusion criteria applicable to all trial parts 
26 
Exclusion criterion 14 was added to exclude patients with 
bradycardia from the trial 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) and AFMPS’s 
request/recommendation (06Apr2022) 
5.2.1 Exclusion criteria applicable to all trial parts 
27 
Exclusion criterion 15 was added to exclude patients with 
family history of sudden cardiac death before age 50 from 
the trial 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) and AFMPS’s 
request/recommendation (06Apr2022) 
5.2.1 Exclusion criteria applicable to all trial parts 
28 
Addition of exclusion criterion no. 19 for all trial parts to 
exclude patients treated with a live or live-attenuated 
vaccine 30 days before treatment administration; 
information about not allowing vaccination with live or 
live-attenuated vaccines during the trial and within 90 
days after the last dose of SOT102 and/or SoC added 
Revised according to the SUKL’s 
recommendation (SUKL RFI 11Feb2022) 
5.2.1 Exclusion criteria applicable to all trial parts; 
6.8.3 Medications requiring special caution 
29 
Exclusion criterion 22 was added for Part B and Part D to 
exclude patients with clinically active inflammatory 
bowel disease from the trial 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) 
5.2.3 Exclusion criteria specific to Part B; 5.2.5 
Exclusion criteria specific to Part D 
30 
Exclusion criterion 25 was added for Part B and Part D 
gastric cohorts to exclude use of medications known to 
prolong QT/QTc interval during the trial 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) and AFMPS’s 
request/recommendation (06Apr2022) 
5.2.3 Exclusion criteria specific to Part B (gastric); 
5.2.5 Exclusion criteria specific to Part D (gastric) 
31 
Exclusion criterion 23 was added for Part B and Part D so 
as not to authorize the inclusion of patients with 
pancreatic adenocarcinoma eligible for FOLFIRINOX 
Revised according to the ANSM’s request/ 
recommendation (17Jun2022) 
5.2.3 Exclusion criteria specific to Part B, 5.2.5 
Exclusion criteria specific to Part D 
32 
A note was added specifying that nivolumab is to be used 
as per the approved label in the respective country 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) 
6.1.2.1 mFOLFOX6 and nivolumab 
33 
Clarification was added that treatment is to be 
discontinued in case a patient develops a DLT, unless the 
patient has a demonstrable clinical benefit from treatment 
at the same time 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) and AFMP’s 
recommendation (11 May 2022) 
6.5.1 Dose modification and toxicity management 
for SOT102 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment 2 
34 
Information was added that caution should be exercised 
when administering trial medication with medications 
known as substrates of CYP2D6 and CYP3A, when 
administering trial medication or nab-paclitaxel with 
QT/QTc interval-prolonging medications; 
recommendation against use of CYP2C8 and CYP3A4 
inducers added for EU in cohorts including nab-paclitaxel 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022), AFMPS’s 
request/recommendation (11May2022), and 
AFMPS’s request/ recommendation 
(06Apr2022) 
6.8.3 Medications requiring special caution; 6.8.3.2 
Nab-paclitaxel 
35 
Clarification was added of the timing of radiology 
assessments throughout the trial 
Revised for better clarity 
8.1.1 Radiologic evaluation of disease 
36 
ECOG collection moved from section on efficacy 
measures (8.1.2) to section on safety (8.2.1) 
Revised for better clarity 
8.2.1 Physical examinations, body height, weight, 
and surface area, ECOG performance status 
37 
In the event of grade ≥3 corrected QT/QTc interval 
prolongation, continuous monitoring of ECG is 
recommended 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) and AFMPS’s 
request/recommendation (06Apr2022) 
8.2.4 Electrocardiography 
38 
Clarification was added to specify the communication 
between the sponsor and investigators regarding SUSARs 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) 
8.3.5 Regulatory reporting requirements for SAEs 
39 
Information on what needs to be documented in eCRF on 
AE page specified (Other suspected cause and Other 
action taken are not to be recorded) 
Revised for better clarity 
8.3.8.2 Documenting in eCRFs 
40 
Clarification was added that both efficacy and safety data 
will be reviewed by the IDMC in Part C and Part D 
Revised according to the ANSM’s request/ 
recommendation (28Mar2022) 
10.1.11 Independent data monitoring committee 
41 
Clarification on sponsor’s contractors being excluded 
from third parties added 
Revised for better clarity 
10.1.12 Future research 
42 
List of CYP2D6 and/or CYP3A substrates included in list 
of medications requiring special caution 
Revised according to the AFMPS’s request/ 
recommendation (06Apr2022) 
10.5 Appendix 5: List of medications requiring 
special caution 
43 
Change of Statistician 
Change of personnel 
SIGNATURES/PROTOCOL APPROVAL AND 
RELEASE SOTIO 
44 
Minor wording and punctuation corrections 
To improve clarity and readability  
Throughout the document 

 
 
 
 
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10.7.5 Amendment FR-2 (22Jun2022): Protocol changes implemented 
Change 
number 
Description of change  
Rationale for change 
Section in Amendment FR-2 
1 
Footnotes 5 and 10 of the schedules of 
activities for Part A and Part B were 
clarified as follows (addition underlined): 
 
“5. Before SOT102 administration in each 
cycle” 
 
“10. Within 15 minutes after the end of 
SOT102 infusion in each cycle; additionally, 
24 hours after the end of SOT102 infusion in 
cycle 1 and cycle 3” 
Revised according to the ANSM’s request/recommendation (17Jun2022): 
 
Due to the risk of QTc interval prolongation observed during preclinical 
studies with SOT102 but also because this is a first in human study, 
Sponsor is asked to modify the protocol, so as to perform a triple ECG at 
T0 (baseline), Tmax (D1) and at steady state (at least 5 product half-lives) 
regularly during part A and B and not as clinically indicated or only at 
cycle 1 and 3 as indicated in the resubmission. It should be done, at least 
Q3W during all escalation parts and could be adapted for expansion 
parts. 
Sections 1.3.1 Schedule of 
activities, Part A (SOT102 
monotherapy, dose escalation, 
CLDN18.2-agnostic), 1.3.2 
Schedule of activities, Part B 
gastric (SOT102 combination 
with first-line SoC treatment, 
dose escalation, CLDN18.2-
agnostic), 1.3.3 Schedule of 
activities, Part B pancreatic 
(SOT102 combination with first-
line SoC treatment, dose 
escalation, CLDN18.2-agnostic) 
2 
The list of exceptions from DLTs in protocol 
section 4.1.1.1 was modified as follows 
(addition underlined): 
 
“Grade 3 or higher amylase or lipase not 
associated with symptoms or clinical 
manifestations or radiological evidence of 
pancreatitis” 
Revised according to the ANSM’s request/recommendation (17Jun2022): 
 
Sponsor is asked to modify section 4.1.1.1 (Dose-Limiting Toxicities 
definitions) so as the DLT exception will be “≥ grade 3 amylase or lipase 
that is not associated with symptoms, or clinical manifestations, or 
radiological imaging of pancreatitis”. Indeed, clinical symptoms are not 
sufficient to detect pancreatitis, imaging is needed when there is grade 3 
amylase or lipase to exclude pancreatitis. The Sponsor has not provided a 
satisfactory response to this point. This is a FIH and a pancreatic toxicity 
cannot be ruled out and as already stated, an imagery is mandatory in 
case of grade 3 amylase or lipase increase. 
Section 4.1.1.1 Dose-limiting 
toxicities definitions 
3 
 
Section 5.2.1 Exclusion criteria applicable to 
all trial parts was modified as follows 
(addition underlined): 
 
“Patient has been previously treated with the 
maximum cumulative dose of 
anthracyclines” 
Revised according to the ANSM’s request/recommendation (17Jun2022): 
 
Concerning exclusion criteria, Sponsor is asked to modify the protocol so 
as to exclude patient previously treated with anthracyclines at the 
maximum cumulative dose. 
Section 5.2.1 Exclusion criteria 
applicable to all trial parts 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment FR-2 
4 
Sections 5.2.3 with exclusion criteria 
specific to Part B and 5.2.5 with exclusion 
criteria specific to Part D were amended as 
follows (addition underlined): 
 
“Patients more clinically suitable (e.g., with 
BRCA1/2 mutation) to receive treatment 
with leucovorin calcium, fluorouracil, 
irinotecan hydrochloride, and oxaliplatin 
(FOLFIRINOX) as compared to nab-
paclitaxel and gemcitabine according to the 
investigator’s opinion” 
Revised according to the ANSM’s request/recommendation (17Jun2022): 
 
Sponsor is asked to modify the inclusion criteria so as not to authorise the 
inclusion of patients with pancreatic adenocarcinoma in part B and D 
eligible for FOLFIRINOX: 
• per Investigator’s opinion. Indeed, a patient may be more clinically 
suitable to receive FOLFIRINOX than nab-paclitaxel and gemcitabine 
according to the investigator. 
• and also because patients with BRCA1/2 mutation will be more sensitive 
to platinum based chemotherapy and so to FOLFIRINOX as according to 
ESMO guidelines 
This two points must be outlined in the protocol. 
Sections 5.2.3 Exclusion criteria 
specific to Part B, 5.2.5 
Exclusion criteria specific to Part 
D 
10.7.6 Amendment BE-2 (26May2022): Protocol changes implemented 
Change 
number 
Description of change  
Rationale for change 
Section in Amendment BE-2 
1 
Stopping rules were moved from section 
4.1.1.7 to section 5.5 and were updated to 
include all trial parts and all cohorts. Section 
4.1.1.7 was removed. 
Revised according to the AFMP’s recommendation (11 May 2022): 
 
R1: The Applicant is recommended to include a separate section in the 
protocol with more specific guidance to investigator for the purpose of 
management of treatment-emergent toxicities. This section could list actions 
toward investigational medication (eg dose reductions, temporary/permanent 
discontinuation), 
additional 
examinations/labs/imaging 
or 
potential 
treatments/referral to specialist 
5.5 Criteria for temporarily 
delaying enrollment/ 
administration of trial 
intervention 
2 
Clarification was added that treatment is to be 
discontinued in case a patient develops a 
DLT, unless the patient has a demonstrable 
clinical benefit from treatment at the same 
time 
Revised according to the AFMP’s recommendation (11May 2022): 
 
R1: The Applicant is recommended to include a separate section in the 
protocol with more specific guidance to investigator for the purpose of 
management of treatment-emergent toxicities. This section could list actions 
toward investigational medication (eg dose reductions, temporary/permanent 
discontinuation), 
additional 
examinations/labs/imaging 
or 
potential 
treatments/referral to specialist 
6.5.1 Dose modification and 
toxicity management for 
SOT102 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment BE-2 
3 
Information was added that caution should be 
exercised 
when 
administering 
trial 
medication medications known as substrates 
of CYP2D6 and CYP3A 
Revised according to the AFMP’s recommendation (11May 2022): 
 
R3: The applicant is asked to include CYP2D6 and CYP3A substrates in 
section 6.8.3 Medications requiring special caution of the protocol 
6.8.3 Medications requiring 
special caution 
4 
Information was added that caution should be 
exercised 
when 
administering 
trial 
medication with QT/QTc interval-prolonging 
medications  
Revised according to the AFMPS’s request/recommendation (11May2022): 
 
C1: Considering the potential for QT prolongation identified for SOT102 in 
the safety pharmacology study in cynomolgus monkeys and the absence of a 
GLP hERG assay. Concomitant therapies with a potential for QT 
prolongation should be used with caution or prohibited in all parts of the trial 
until the QT prolongation potential of SOT102 is further characterized. The 
relevant wording should be included in the protocol. 
6.8.3 Medications requiring 
special caution 
10.7.7 Amendment BE-1 (03May2022): Protocol changes implemented 
Change 
number 
Description of change  
Rationale for change 
Section in Amendment BE-1 
1 
Monitoring of SaO2 was added to the 
assessments to be performed in the trial for all 
trial parts and all cohorts 
Revised according to the AFMPS’s request/recommendation (06Apr2022): 
 
Question 7: In the primary PD section, CLDN18.2 expression was seen in 
lung xenograft models and microscopic findings were seen in the rat repeat 
dose studies indicating a potential for on target effect in the lungs. In 
addition some of the SOC therapies are associated with a potential for lung/ 
respiratory AE. The applicant is asked to include specific monitoring in the 
protocol to detect early lung adverse events as well as management 
guidelines (clear cut-off value to trigger study drug discontinuation, the 
timing and frequency of follow-up assessments to monitor after an abnormal 
result and conditions needed to restart treatment) for all parts of the trial. 
1.3.1 – 1.3.6 Schedule of 
activities (Part A, Part B, Part C, 
Part D) 
2 
Monitoring of LVEF schedule for Part B was 
aligned with that of Part A. Monitoring of 
LVEF was added to the assessments to be 
performed at 30 (±5) days after the last dose 
Revised according to the AFMPS’s request/recommendation (06Apr2022): 
 
Question 2: The stomach, liver, kidney have been identified as potential 
target organs for SOT102 toxicity, and non-adverse prolonged QT interval 
was seen in monkeys. These toxicities also overlap with the potential AE of 
1.3.2 – 1.3.6 Schedule of 
activities (Part B, Part C, Part D) 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment BE-1 
of SOT102 for trial Part B, Part C, and Part 
D, all cohorts 
the standard of care therapies. The applicant should thoroughly justify the 
rationale for the reduced monitoring frequency in part B and D pancreatic 
cohort. Especially in part B given this will be the first administration of 
SOT102 with SOC therapies. Safety monitoring including physical exams, 
vital signs (before, during, after end of infusion), biochemistry, urinalysis, 
creatinine clearance, ECG (around T max) should be conducted at least at 
each SOT102 administration (every 14 days,) similarly to the gastric 
cohorts. In addition, LVEF currently only monitored in part A should be 
added to the part B, C and D or its absence thoroughly justified. 
3 
Schedule of pregnancy testing during the trial 
was clarified in Part B pancreatic and Part D 
pancreatic 
Revised according to the AFMPS’s request/recommendation (06Apr2022): 
 
Question 8: In accordance with the “Recommendations related to 
contraception and pregnancy testing in clinical trials” of the Clinical trial 
facilitation 
group 
(CTFG) 
available 
at 
the 
HMA 
website: 
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contracepti
on.pdf, the applicant is asked to implement monthly pregnancy testing until 
the expected end of exposure (5 half-lives) + 6 months. In addition due to 
the potential of SOT102 to affect male reproductive organs, the applicant is 
asked to include a recommendation for sperm preservation for patients 
wishing to become a father in the protocol. 
1.3.3 Schedule of activities (Part 
B pancreatic), 1.3.6 Schedule of 
activities (Part D pancreatic) 
4 
Schedule of physical exams, vital signs, 
biochemistry, 
urinalysis, 
creatinine 
clearance, and ECG determinations was 
clarified in Part B pancreatic and Part D 
pancreatic 
Revised according to the AFMPS’s request/recommendation (06Apr2022): 
 
Question 2: The stomach, liver, kidney have been identified as potential 
target organs for SOT102 toxicity, and non-adverse prolonged QT interval 
was seen in monkeys. These toxicities also overlap with the potential AE of 
the standard of care therapies. The applicant should thoroughly justify the 
rationale for the reduced monitoring frequency in part B and D pancreatic 
cohort. Especially in part B given this will be the first administration of 
SOT102 with SOC therapies. Safety monitoring including physical exams, 
vital signs (before, during, after end of infusion), biochemistry, urinalysis, 
creatinine clearance, ECG (around T max) should be conducted at least at 
each SOT102 administration (every 14 days,) similarly to the gastric 
1.3.3 Schedule of activities (Part 
B pancreatic), 1.3.6 Schedule of 
activities (Part D pancreatic) 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment BE-1 
cohorts. In addition, LVEF currently only monitored in part A should be 
added to the part B, C and D or its absence thoroughly justified. 
5 
In the event of grade ≥3 corrected QT/QTc 
interval prolongation, continuous monitoring 
of ECG is recommended 
Revised according to the AFMPS’s request/recommendation (06Apr2022): 
 
Question 4: In the protocol the fact that “Concomitant use of drugs known 
to prolong the QT/QTc interval is prohibited during the trial.” is only listed 
in relation to mFOLFOX6 and in the appendix 5 concerned drugs appear 
under the list of medications requiring special cautions. Considering the 
potential for QT prolongation identified in the safety pharmacology study, 
drugs with a potential for QT prolongation should be prohibited for the 
entire trial. The applicant is asked to modify the protocol and appendix 5 
accordingly. 
4.1.1.1 Dose-limiting toxicities 
definitions 
6 
Discontinuation from therapy mandated for 
patients who develop toxicities qualified as 
DLTs 
Revised according to the AFMPS’s request/recommendation (06Apr2022): 
 
Question 1: As this is a FIH trial for SOT102 (IgG1 based) and considering 
that nivolumab has also been associated with some infusion related 
reactions, the applicant is asked to include in the protocol management 
guidelines and stopping rules for infusion related reactions and cytokine 
release syndrome, in addition the length of patient observation after the end 
of infusion in each part should be clearly stated and justified 
4.1.1.1 Dose-limiting toxicities 
definitions 
7 
Inclusion 
criterion 
3.7 
on 
serum 
concentrations of potassium, magnesium, and 
calcium within normal range was added 
Revised according to the AFMPS’s request/recommendation (06Apr2022): 
 
Question 4: In the protocol the fact that “Concomitant use of drugs known 
to prolong the QT/QTc interval is prohibited during the trial.” is only listed 
in relation to mFOLFOX6 and in the appendix 5 concerned drugs appear 
under the list of medications requiring special cautions. Considering the 
potential for QT prolongation identified in the safety pharmacology study, 
drugs with a potential for QT prolongation should be prohibited for the 
entire trial. The applicant is asked to modify the protocol and appendix 5 
accordingly. 
5.1.1 Inclusion criteria 
applicable to all trial parts 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment BE-1 
8 
Exclusion criterion 14 was added to exclude 
patients with bradycardia from the trial 
Revised according to the AFMPS’s request/recommendation (06Apr2022): 
 
Question 4: In the protocol the fact that “Concomitant use of drugs known 
to prolong the QT/QTc interval is prohibited during the trial.” is only listed 
in relation to mFOLFOX6 and in the appendix 5 concerned drugs appear 
under the list of medications requiring special cautions. Considering the 
potential for QT prolongation identified in the safety pharmacology study, 
drugs with a potential for QT prolongation should be prohibited for the 
entire trial. The applicant is asked to modify the protocol and appendix 5 
accordingly. 
5.2.1 Exclusion criteria 
applicable to all trial parts 
9 
Exclusion criterion 15 was added to exclude 
patients with family history of sudden cardiac 
death before age 50 from the trial 
Revised according to the AFMPS’s request/recommendation (06Apr2022): 
 
Question 4: In the protocol the fact that “Concomitant use of drugs known 
to prolong the QT/QTc interval is prohibited during the trial.” is only listed 
in relation to mFOLFOX6 and in the appendix 5 concerned drugs appear 
under the list of medications requiring special cautions. Considering the 
potential for QT prolongation identified in the safety pharmacology study, 
drugs with a potential for QT prolongation should be prohibited for the 
entire trial. The applicant is asked to modify the protocol and appendix 5 
accordingly. 
5.2.1 Exclusion criteria 
applicable to all trial parts 
10 
Exclusion criterion 22 was added for Part B 
and Part D gastric cohorts to exclude use of 
medications known to prolong QT/QTc 
interval during the trial 
Revised according to the AFMPS’s request/recommendation (06Apr2022): 
 
Question 4: In the protocol the fact that “Concomitant use of drugs known 
to prolong the QT/QTc interval is prohibited during the trial.” is only listed 
in relation to mFOLFOX6 and in the appendix 5 concerned drugs appear 
under the list of medications requiring special cautions. Considering the 
potential for QT prolongation identified in the safety pharmacology study, 
drugs with a potential for QT prolongation should be prohibited for the 
entire trial. The applicant is asked to modify the protocol and appendix 5 
accordingly. 
5.2.3 Exclusion criteria specific 
to Part B (gastric); 5.2.5 
Exclusion criteria specific to Part 
D (gastric) 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment BE-1 
11 
Recommendation against use of CYP2C8 and 
CYP3A4 
inducers 
added 
for 
cohorts 
including nab-paclitaxel 
Revised according to the AFMPS’s request/recommendation (06Apr2022): 
 
Question 5: The applicant is asked to modify the protocol to clarify that 
CYP2C8 et CYP3A4 inducers are not recommended instead of authorized 
with caution in cohorts including nab-paclitaxel. 
6.8.3.2 Nab-paclitaxel 
12 
List of CYP2D6 and/or CYP3A substrates 
included in list of medications requiring 
special caution 
Revised according to the AFMPS’s request/recommendation (06Apr2022): 
 
Recommendation 2: The applicant is asked to include CYP2D6 and CYP3A4 
substrates to the concomitant therapies to use with caution as these may be 
inhibited by 
 
10.5 Appendix 5: List of 
medications requiring special 
caution 
13 
Change of Statistician 
Change of personnel 
SIGNATURES/ 
PROTOCOL APPROVAL AND 
RELEASE SOTIO 
10.7.8 Amendment FR-1 (26Apr2022): Protocol changes implemented 
Change 
number 
Description of change  
Rationale for change 
Section in Amendment FR-1 
1 
A note was added to the trial design schema 
to clarify the patient population in Part B and 
Part D of the trial. In addition, exclusion 
criterion 17 for Part B and Part D was updated 
to clarify the same 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.11 Sponsor is asked to modify the protocol in order to clarify the lines of 
therapy required prior enrollments into Parts B and D in inclusion criteria 
as already requested by FDA, this not clear. According to the schema of 
design, patient should not have prior therapies in metastatic setting. 
1.2 Schema; 5.2.3 Exclusion 
criteria specific to Part B; 5.2.5 
Exclusion criteria specific to Part 
D 
2 
Monitoring of SaO2 was added to the 
assessments to be performed in the trial for all 
trial parts and all cohorts 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.8 Concerning monitoring of patient, considering that this is a first in 
human trial and safety of patient must be the priority, Sponsor is asked to: 
Add a monitoring of SaO2 for all parts as pulmonary toxicities have been 
shown in preclinical studies and are expected with standard of care 
1.3.1 – 1.3.6 Schedule of 
activities (Part A, Part B, Part C, 
Part D) 

 
 
 
 
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number 
Description of change  
Rationale for change 
Section in Amendment FR-1 
3 
Monitoring of HIV and HBV for HIV and/or 
HBV-positive patients was added to the 
assessments to be performed in the trial for all 
trial parts and all cohorts 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.8 Concerning monitoring of patient, considering that this is a first in 
human trial and safety of patient must be the priority, Sponsor is asked to: 
Add monitoring of HBV and HIV serology as clinically indicated as patients 
with history of such infections can be included and risk of reactivation 
cannot be escluded 
1.3.1 – 1.3.6 Schedule of 
activities (Part A, Part B, Part C, 
Part D); 10.4.3 Clinical 
chemistry 
4 
Monitoring of AEs considered as having a 
suspected causal relationship to SOT102 per 
the investigator’s judgment and monitoring 
of concomitant medication was added to the 
follow-up until disease progression or start of 
new anticancer therapy in Part A and Part B 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.8 Concerning monitoring of patient, considering that this is a first in 
human trial and safety of patient must be the priority, Sponsor is asked to: 
extend the period of data collection of AE/SAE related to treatment at follow 
up every 6 weeks and not only at 30 days post-EOT. Indeed considering the 
half-life of the product and the potential risk of delayed toxicities, the follow-
up period of AE monitoring is not appropriate. If necessary, this long-term 
safety follow-up may be planned as a phone call visit to avoid additional 
hospital visit and burden for patients who might be followed in another site 
after study treatment discontinuation. Survival and concomitant therapies 
should also be followed in part A and B 
1.3.1 – 1.3.3 Schedule of 
activities (Part A, Part B); 4.1.2.4 
Follow-up period (Part A); 
4.1.3.4 Follow-up period (Part 
B); 8.3.2 Time period and 
frequency for collecting AE, 
SAE, and other reportable safety 
event information 
5 
Monitoring of LVEF schedule for Part B was 
aligned with that of Part A 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.8 Concerning monitoring of patient, considering that this is a first in 
human trial and safety of patient must be the priority, Sponsor is asked to: 
add a monitoring of LVEF every 2 cycles for part B as it is planned for part 
A. Indeed, combinations has never been tested in a clinical setting, and 
cardiac toxicity related to anthracyclin cannot be excluded. 
1.3.2, 1.3.3 Schedule of activities 
(Part B gastric, Part B 
pancreatic) 
6 
Monitoring of LVEF was added to the 
assessments to be performed at 30 (±5) days 
after the last dose of SOT102 for trial Part B, 
Part C, and Part D, all cohorts 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.8 Concerning monitoring of patient, considering that this is a first in 
human trial and safety of patient must be the priority, Sponsor is asked to: 
Add an end of treatment visit during which most of the parameters followed 
during treatment will be assess (coagulation, vital signs, physical 
examination, biochemistry, hematology, urinalysis, creatinine clearance, 
AE, LVEF) 
1.3.2 – 1.3.6 Schedule of 
activities (Part B, Part C, Part D) 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment FR-1 
7 
Number of patients to be treated at the RP2D 
before opening expansion cohorts was 
clarified 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.10 Sponsor is asked to clarify in the protocol that at least 6 patients 
evaluable for DLT will be treated at the RP2D before opening expansion 
parts as also requested by FDA (for both part A and B). Indeed, the wording 
is not clear in the protocol 
4.1.1 Dose escalation plan (Part 
A and Part B); 4.1.1.2 Maximum 
tolerated dose and selection of 
the recommended phase 2 dose; 
9.5.1 Part A (SOT102 
monotherapy, dose escalation); 
9.5.2 Part B (SOT102 combined 
with first-line SoC treatment, 
dose escalation) 
8 
In the event of grade ≥3 corrected QT/QTc 
interval prolongation, continuous monitoring 
of ECG is recommended 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.5 Sponsor is asked to modify the protocol, due to the risk of QTc interval 
prolongation observed during preclinical studies with SOT102 but also 
because this is a first in human study and combinations have never been 
tested in preclinical studies so safety of monotherapy and combinations is 
not known: so as to provide for the following in the event of QT/QTc interval 
prolongation greater than 500 ms (grade 3 toxicity): initiation of close and 
appropriate ECG monitoring (continuously) in hospital until a 
cardiologist’s opinion is issued 
4.1.1.1 Dose-limiting toxicities 
definitions 
9 
Communication plan between the sponsor, 
the investigators, and the subjects in the event 
of emerging safety issues was updated  
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.16 The sponsor is asked to modify the protocol so as to describe: the 
communication plan between the sponsor, the investigators and the subjects 
participating in the trial, in the event of emerging safety issues 
4.1.1.6 Communication plan  
10 
Stopping rules were moved from section 
4.1.1.7 to section 5.5 and were updated to 
include all trial parts and all cohorts. Section 
4.1.1.7 was removed. 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.6 Sponsor must define in the protocol unambiguous safety stopping rules 
for expansion parts and entire study that result in discontinuation of 
enrollment in case of unexpected toxicity signal observed. This demand is in 
accordance with the GCP applicable to all clinical trials regardless of the 
development phase (ICH E6, section 6.4: "A description of the trial design, 
should include [...] A description of the stopping rules or discontinuation 
criteria for individual subjects, parts of trial and entire trial") and the 
recommendations of the "guideline on strategies to identify and mitigate 
5.5 Criteria for temporarily 
delaying 
enrollment/administration of trial 
intervention 

 
 
 
 
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number 
Description of change  
Rationale for change 
Section in Amendment FR-1 
risks for first-in-human and early clinical trials with investigational 
medicinal products" (section 8.2.9). 
Stopping rules criteria must be based on safety parameters such as the 
frequency and severity of adverse events and these parameters must be 
specified in the protocol. These rules a priori will be followed by the safety 
committee to take the temporary stopping decisions before final decision 
(e.g. permanent discontinuation, dose reduction of a treatment in the 
combination or adaptation of the monitoring plan). The rules may be 
applied for each cohorts in a way to be able to continue some cohorts while 
others are stopped. 
11 
Inclusion 
criterion 
3.7 
on 
serum 
concentrations of potassium, magnesium, and 
calcium within normal range was added 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.4 Concerning exclusion criteria, as this is a FIH trial and some patients 
will be treated in first line, Sponsor is asked to modify the protocol so as to: 
Exclude patient with marked and persistent bone marrow depression and/or 
severe stomatitis induced by previous cytotoxic and/or radiotherapy 
treatment (including in patients at high risk of bleeding), acute 
inflammatory heart disease, previous treatment with an anthracycline at the 
maximum cumulative dose and hypersensitivity to anthracycline 
5.1.1 Inclusion criteria 
applicable to all trial parts 
12 
Inclusion criterion 6.2 was modified to 
specify that a highly effective contraceptive 
method must be used during the treatment 
period and for at least 9 months after the last 
dose of SOT102 or first-line SoC treatment 
(whichever occurs later). 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.9 Concerning the contraception, in accordance with the recommendations 
of the CTFG regarding pregnancy risk management (Recommendations 
related to contraception and pregnancy testing in clinical trials), Sponsor is 
asked to modify the protocol in order to: Take in account duration of 
contraception according to each chemotherapies and nivolumab in case that 
the last drug administered is not SOT102 
5.1.1 Inclusion criteria 
applicable to all trial parts 
13 
Inclusion criterion 7 was modified to specify 
that a highly effective contraceptive method 
must be used by WOCBP partners of male 
participants 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.9 Concerning the contraception, in accordance with the recommendations 
of the CTFG regarding pregnancy risk management (Recommendations 
related to contraception and pregnancy testing in clinical trials), Sponsor is 
asked to modify the protocol in order to: Take in account duration of 
5.1.1 Inclusion criteria 
applicable to all trial parts 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment FR-1 
contraception according to each chemotherapies and nivolumab in case that 
the last drug administered is not SOT102 
14 
Exclusion criterion 7 was updated to specify 
that an active infection must be clinically 
controlled before patient’s inclusion in the 
trial 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.4 Concerning exclusion criteria, as this is a FIH trial and some patients 
will be treated in first line, Sponsor is asked to modify the protocol so as to: 
Modify exclusion criteria 7 by specifying that infection must be controlled 
with antibiotics before inclusion 
5.2.1 Exclusion criteria 
applicable to all trial parts 
15 
Exclusion criterion 11 was updated to specify 
that patients with NYHA ≥2 heart failure 
must be excluded from the trial 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.4 Concerning exclusion criteria, as this is a FIH trial and some patients 
will be treated in first line, Sponsor is asked to modify the protocol so as to: 
Modify exclusion criteria 11 in order to exclude patient with NYHA≥2 heart 
failure, this a FIH trial with a product in monotherapy or in combination 
with expected cardiac toxicities 
5.2.1 Exclusion criteria 
applicable to all trial parts 
16 
Exclusion criterion 14 was added to exclude 
patients with bradycardia from the trial 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.5 Sponsor is asked to modify the protocol, due to the risk of QTc interval 
prolongation observed during preclinical studies with SOT102 but also 
because this is a first in human study and combinations have never been 
tested in preclinical studies so safety of monotherapy and combinations is 
not known: so as not to enable the inclusion of patients who present the 
following in this trial: bradycardia (< 50 beats per minute) 
5.2.1 Exclusion criteria 
applicable to all trial parts 
17 
Exclusion criterion 15 was added to exclude 
patients with family history of sudden cardiac 
death before age 50 from the trial 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.5 Sponsor is asked to modify the protocol, due to the risk of QTc interval 
prolongation observed during preclinical studies with SOT102 but also 
because this is a first in human study and combinations have never been 
tested in preclinical studies so safety of monotherapy and combinations is 
not known: so as not to enable the inclusion of patients who present the 
following in this trial: family history of sudden cardiac death before age 50 
5.2.1 Exclusion criteria 
applicable to all trial parts 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment FR-1 
18 
Exclusion criterion 19 was added for Part B 
and Part D to exclude patients with clinically 
active inflammatory bowel disease from the 
trial 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.4 Concerning exclusion criteria, as this is a FIH trial and some patients 
will be treated in first line, Sponsor is asked to modify the protocol so as to: 
Precise exclusion of patients with IBD 
5.2.3 Exclusion criteria specific 
to Part B; 5.2.5 Exclusion 
criteria specific to Part D 
19 
Exclusion criterion 22 was added for Part B 
and Part D gastric cohorts to exclude use of 
medications known to prolong QT/QTc 
interval during the trial 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.4 Concerning exclusion criteria, as this is a FIH trial and some patients 
will be treated in first line, Sponsor is asked to modify the protocol so as to: 
Exclude patient with concomitant use of drugs known to prolong QT/QTc 
interval in association with mFOLFOX6 to be in accordance with section 
6.8.3.1 
5.2.3 Exclusion criteria specific 
to Part B (gastric); 5.2.5 
Exclusion criteria specific to Part 
D (gastric) 
20 
A note was added specifying that nivolumab 
is to be used as per the approved label in the 
respective country 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.2 Sponsor is asked to modify the protocol so as to comply with the updated 
SPC of nivolumab which have the indication in patients with gastric/GEJ 
adenocarcinoma with PD-L1 CPS ≥ 5, this parameter must be specify in 
inclusion criteria 
6.1.2.1 mFOLFOX6 and 
nivolumab 
21 
Clarification was added that treatment is to be 
discontinued in case a patient develops a 
DLT, unless the patient has a demonstrable 
clinical benefit from treatment at the same 
time 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.14 Sponsor is asked to modify in the protocol so as to clarify that 
occurrence of a DLT will lead to treatment discontinuation as no dose 
reduction or treatment delay are allowed in part A and B in the first two 
cycles according to section 6.5.1 
6.5.1 Dose modification and 
toxicity management for 
SOT102 
22 
Information was added that caution should be 
exercised 
when 
administering 
trial 
medication or nab-paclitaxel with QT/QTc 
interval-prolonging medications 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.5 Sponsor is asked to modify the protocol, due to the risk of QTc interval 
prolongation observed during preclinical studies with SOT102 but also 
because this is a first in human study and combinations have never been 
tested in preclinical studies so safety of monotherapy and combinations is 
not known: so as to mention in the concomitant treatments section that drugs 
known to cause QTc interval prolongation must be used with precaution for 
all part except in gastric cohorts since they are prohibited 
6.8.3 Medications requiring 
special caution; 6.8.3.2 Nab-
paclitaxel 

 
 
 
 
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number 
Description of change  
Rationale for change 
Section in Amendment FR-1 
23 
Clarification was added to specify the 
communication between the sponsor and 
investigators regarding SUSARs 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.16 The sponsor is asked to modify the protocol so as to describe: the plan 
for rapid communication of suspected unexpected serious adverse reactions 
(SUSARs) between the sponsor, the investigators of all sites and the patients 
in accordance with the "Guideline on strategies to identify and mitigate 
risks for first-in-human and early clinical trials with investigational 
medicinal products" section 8.2.10 
8.3.5 Regulatory reporting 
requirements for SAEs 
24 
Clarification was added that both efficacy 
and safety data will be reviewed by the IDMC 
in Part C and Part D 
Revised according to the ANSM’s request/recommendation (28Mar2022): 
 
3.17 Sponsor is asked to add an interim analysis including efficacy 
parameters in order to be able to stop the study in case of lack of efficacy in 
accordance with “Guideline for good clinical practice E6” section 1.32 and 
5.4.1. This is highly recommended especially since this is a multicentre FIH 
trial. 
10.1.11 Independent data 
monitoring committee 
25 
Change of Statistician 
Change of personnel 
SIGNATURES/ 
PROTOCOL APPROVAL AND 
RELEASE SOTIO 
 
10.7.9 Amendment CZ-1 (01Mar2022): Protocol changes implemented 
Change 
number 
Description of change  
Rationale for change 
Section in Amendment CZ-1 
1 
Addition of exclusion criterion no. 16 for all 
trial parts 
Revised according to the SUKL’s recommendation (SUKL RFI 
11Feb2022): 
We require that you add to the exclusion criteria that patients who would 
be vaccinated with a live vaccine 30 days prior to the administration of the 
1st dose, then during and 90 days after the end of the CT, may not be 
enrolled. 
Section 5.2.1 Exclusion criteria 
applicable to all trial parts 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment CZ-1 
2 
Change of Statistician 
Change of personnel 
SIGNATURES/ 
PROTOCOL APPROVAL AND 
RELEASE SOTIO 
10.7.10 Amendment 1 (14Jan2022): Protocol changes implemented 
Change 
number 
Description of change  
Rationale for change 
Section in Amendment 1 
1 
PK sampling schedule revised to include 
separate sampling schedule for Part C and 
Part D 
Revised according to the FDA’s recommendation (FDA RFI 12Jan2022): 
Specific pharmacokinetic (PK) sampling time points in Part C and D. The 
sparse PK sampling collected in Part C and D should allow for population 
PK and exposure-response analyses to facilitate SOT102 dose selection. 
The PK sampling time points should include Cmax after the first dose as well 
as Cmax and Ctrough at steady state. 
Section 1.3.8 PK and ADA 
sampling (SOT102) for Part C 
and Part D; sections 1.3.4 – 1.3.6 
Schedule of activities Part C, 
Part D gastric, Part D pancreatic 
2 
PK analysis plan revised to include all 
analytes as listed in Objectives. 
Revised according to the FDA’s recommendation (FDA RFI 12Jan2022): 
Revise the protocol to include total SOT102, conjugated SOT102, 
in the PK 
analysis plan (Page 77). 
Section 8.4 Pharmacokinetics 
3 
Warning about use of medications that are 
known inhibitors or inducers of CYP3A4 or 
CYP2C9 for Part A and Part B added. 
Revised based on the FDA’s recommendation (FDA RFI 12Jan2022): 
Avoid concomitant use of medications that are known inhibitors or inducers 
of CYP3A4 or CYP2C9 in Part A and B to minimize any potential effect on 
 and 
-linker containing metabolites exposure. Revise the 
protocol to monitor adverse events closely when administering SOT102 with 
medications that are known inhibitors or inducers of CYP3A4 or CYP2C9 
in Part C and D. 
Section 6.8.3 Medications 
requiring special caution; section 
10.5 List of medications 
requiring special caution 

 
 
 
 
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Description of change  
Rationale for change 
Section in Amendment 1 
4 
ECG measurement schedule clarified for Part 
A and Part B. Possible revision of ECG 
measurement schedule added for Part C and 
Part D. 
Revised based on the FDA’s recommendation (FDA RFI 12Jan2022): 
Collect ECG at baseline (screening), pre-dose and around time of maximum 
drug concentration (Tmax) after the first dose and at steady state, 
periodically during the study, and as clinically indicated in Part A and B. 
Revise the protocol to re-evaluate the ECG collection plan in Part C and D 
with the emerging data form Part A and B. 
Section 8.2.4 
Electrocardiography sections 
1.3.1 – 1.3.3 Schedule of 
activities Part A, Part B gastric, 
Part B pancreatic 
5 
Inclusion criterion no. 15 revised for clarity 
Revised based on the FDA’s recommendation (FDA RFI 13Jan2022): 
Inclusion criteria #15 is unclear and may be subjectively interpreted. 
Modify this inclusion criterion to state: Patient has received and/or has 
been determined to be intolerant of all standard of care therapy known to 
confer clinical benefit. 
Section 1.1 Synopsis; Section 
5.1.2 Inclusion criteria specific 
to Part A  
6 
Definition of what constitutes an exception to 
DLTs was modified 
Revised based on the FDA’s recommendation (FDA RFI 13Jan2022): 
The following is not an acceptable DLT exception and should be removed: 
a. Grade 3 aspartate transaminase (AST) or alanine transaminase (ALT) or 
grade 3 bilirubinemia that lasts ≤5 days 
Section 4.1.1.1 Dose-limiting 
toxicities definitions 
7 
Dose modification and toxicity management 
for SOT102 and first-line SoC revised to 
provide more guidance 
Revised based on the FDA’s recommendation (FDA RFI 13Jan2022): 
Modify the trial to include specific dose modification guidelines for SOT102  
based on NCI CTCAE v5.0 grade of observed toxicity. These dose 
modification guidelines should include the following: 
a. Instructions on when to hold and permanently discontinue study 
treatment based on toxicity 
i. (i.e. treatment interruptions for Grade 3+ and intolerable or persistent 
Grade 2 AE that occur after the DLT evaluation period in Parts A and B 
and for the duration of treatment in Parts C and D) 
Section 6.5.1 Dose modification 
and toxicity management for 
SOT102; section 6.5.2 Dose 
modification and toxicity 
management for first-line SoC 
treatment 

 
 
 
 
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Section in Amendment 1 
ii. Permanent discontinuation of study treatment for Grade 4 adverse 
events 
b. Instructions on when study treatment may be restarted (i.e. upon 
resolution of AE to grade ≤1 or baseline) 
d. Instructions for management of recurrent toxicity 
e. Instructions for managing combination regimen when AE cannot be 
clearly attributed to one drug in the combination (i.e. recommendations 
describing which drugs to hold initially in response to AE versus 
recommendation to hold all drugs in the combination) 
f. Guidelines should include a maximum allowable period (i.e. 2 weeks or 1 
cycle) in which toxicity must resolve before study treatment is discontinued. 
8 
Schedule of patient monitoring clarified in 
Schedule of activities for Part A 
Revised based on the FDA’s recommendation (FDA RFI 13Jan2022): 
In the schedule of activities listed in 1.3.1 for Part A, the frequency in which 
patient monitoring (i.e. physical exams, AE assessment) will occur is 
unclear. Clarify whether patients will receive the assessments listed on both 
Day 1 and Day 8 of each 14-day cycle or on Day 1 of each cycle only. 
Section 1.3.1 Schedule of 
activities, Part A 
9 
Exclusion criterion no. 8 on HIV, hepatitis B, 
and hepatitis C patients revised to allow their 
participation under specific circumstances 
Revised based on the FDA’s recommendation (FDA RFI 13Jan2022): 
The FDA generally recommends against blanket exclusion of patients with 
HIV, Hepatitis B or Hepatitis C on clinical trials. See: FDA Guidance to 
Industry on Cancer Clinical Trial Eligibility Criteria: Patients with HIV, 
Hepatitis 
B 
Virus, 
or 
Hepatitis 
C 
Virus 
Infections 
(https://www.fda.gov/media/121319/download) 
Section 5.2.1 Exclusion criteria 
applicable to all trial parts 
10 
Inclusion criterion no. 13 for Part A and Part 
C revised to remove time-based washout and 
recovery period 
Revised based on the FDA’s recommendation (FDA RFI 13Jan2022): 
FDA generally recommends against time-based washout and recovery 
periods within the eligibility criteria unless scientifically justified. 
Eligibility should be determined based on patient recovery from clinically 
significant adverse events from their most recent therapy or intervention 
Section 5.1.2 Inclusion criteria 
specific to Part A; section 5.1.4 
Inclusion criteria specific to Part 
C 

 
 
 
 
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Change 
number 
Description of change  
Rationale for change 
Section in Amendment 1 
prior to study enrollment. Although not official FDA guidance, you may 
refer to recent publication from ASCO and FOCR for further rationale 
(https://clincancerres.aacrjournals.org/content/27/9/2400). 
 

 
 
 
 
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10.8 Appendix 8: Country-specific requirements/differences 
Country 
Section(s) in Protocol 
Amendment 5 
Country-specific 
requirements/differences 
France (per country-
specific amendment 
FR-3 dated 01Sep2022) 
5.1 Inclusion criteria, 
criterion 12 
All previous cancer therapies for 
locally advanced pancreatic cancer and 
any agents that have not received 
regulatory approval for any indication 
must have been discontinued for ≥21 
days or ≥5 half-lives, whichever is 
longer. Patients must have recovered 
from the acute effects of therapy and 
treatment-related toxicities must have 
reached grade ≤1 (exception: alopecia). 
Mitomycin-C and nitrosoureas must 
have been discontinued for ≥42 days. 
10.4.3 Clinical 
chemistry 
Cholesterol, fibrinogen, and 
triglycerides are to be evaluated at 
screening, prior to each cycle, and at 30 
(+5) days after the last dose of SOT102 
under fasting conditions. 
 
 

 
 
 
 
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