A Randomized, Open-Label, Phase 3 Trial of Tisotumab Vedotin vs Investigator's Choice Chemotherapy in Second- or Third-Line Recurrent or Metastatic Cervical Cancer
Phase: PHASE3
Conditions: Cervical Cancer
Sponsor: Seagen, a wholly owned subsidiary of Pfizer

 
This document contains information proprietary to Seagen Inc. The information is being 
provided to you for the purpose of conducting a clinical trial for Seagen Inc. You may disclose 
the contents of this document to trial personnel under your supervision and to your Institutional 
Review Board (IRB) or Ethics Committee (EC) for the same purpose. You may not disclose the 
contents of this document to any other party, unless government regulations or laws require such 
disclosure, without prior written permission from Seagen Inc. Any supplemental information that 
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disclosure procedure described above. 
 
Study SGNTV-003 
Clinical Protocol Amendment 4 
22-Jan-2024 
Tisotumab vedotin 
Seagen Inc. – Confidential 
Page 1 of 115 
TITLE PAGE  
Protocol Title: 
A Randomized, Open-Label, Phase 3 Trial of Tisotumab 
Vedotin vs Investigator’s Choice Chemotherapy in Second- 
or Third-Line Recurrent or Metastatic Cervical Cancer 
Protocol Number: 
SGNTV-003 
Version; Date of Protocol: 
Amendment 4; dated  22-Jan-2024 
Study Name: 
innovaTV 301 
Investigational Drug: 
Tisotumab vedotin 
Study Phase: 
3 
Short Title:  
Phase 3 Trial of Tisotumab Vedotin vs Chemotherapy in 
Recurrent or Metastatic Cervical Cancer 
Sponsor Name and Address: 
Seagen Inc.* 
21823 30th Drive SE 
Bothell, WA 98021, USA 
*Please note that as of 14-Dec-2023, Seagen Inc. became 
part of Pfizer Inc. 
Collaborator Name and 
Address: 
Genmab A/S 
Kalvebod Brygge 43 
DK-1560 Copenhagen V 
Denmark 
IND No.: 
135476 
EudraCT No.: 
2019-001655-39 
EU Trial No.: 
2023-503813-31 

Protocol 
 
SGNTV-003 
Study SGNTV-003 
Clinical Protocol Amendment 4 
22-Jan-2024 
Tisotumab vedotin 
Seagen Inc. – Confidential 
Page 2 of 115 
Medical Monitors: 
 
Seagen Inc. 
Tel: 
 
Email: 
 
 
Seagen Inc. 
Tel: 
 
Email: 
 
ENGOT Study No. 
ENGOT-cx12 
 
GOG Study No.  
GOG-3057 
 

Protocol 
 
SGNTV-003 
Study SGNTV-003 
Clinical Protocol Amendment 4 
22-Jan-2024 
Tisotumab vedotin 
Seagen Inc. – Confidential 
Page 3 of 115 
DOCUMENT HISTORY AND SUMMARY OF CHANGES  
DOCUMENT HISTORY 
Document 
Date 
Original protocol 
17-Sep-2020 
Amendment 1 
23-Nov-2020 
Amendment 2 
20-Aug-2021 
Amendment 3 
06-Apr-2022 
Amendment 4 
22-Jan-2024 
Amendment 1  
This amendment is considered to be nonsubstantial based on the criteria set forth in Article 10(a) 
of Directive 2001/20/EC of the European Parliament and the Council of the European Union 
because it neither significantly impacts the safety or physical/mental integrity of participants nor 
the scientific value of the study. 
Protocol Amendment Summary of Changes Table: Amendment 1  
 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis, 1.2 Study 
Schema, 1.3 Schedule of 
Activities, 2.1.3 Control 
Arm, 4.3 Justification for 
Dose, 6 Study Intervention, 
10.7.5 Recommended Dose 
Modifications for 
Pemetrexed 
Pemetrexed added as an option for 
investigator’s choice chemotherapy arm 
Increase treatment flexibility for 
investigators with participants in 
the comparator arm 
6.6.1.2 Dose Delay for 
Tisotumab Vedotin, 7.1.1 
Summary of Safety 
Stopping Rules 
Duration of tisotumab vedotin dose delay 
due to toxicity changed from 12 weeks to 6 
weeks before treatment is discontinued 
Enhancement of participant safety 
1.3, Schedule of Activities 
Biomarker and PRO collection timepoints 
made identical for both treatment arms 
Correction 
5.3, Lifestyle 
Considerations 
Added lifestyle recommendations to avoid 
contributing factors to the development of 
dry eye 
Enhancement of participant safety 
Throughout protocol 
Sponsor company name updated 
Seattle Genetics has changed its 
name to “Seagen Inc” 
1.1 Synopsis, 4.2 Scientific 
Rationale for Study Design 
Description of IDMC edited to be consistent 
with wording used in Section 9.8.1 
Consistency of language 
throughout protocol 
1.1 Synopsis, 5 Study 
Population 
Participant number description changed to 
the number randomized; Definition of 
“Enrolled” removed 
Clarification  

Protocol 
 
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Clinical Protocol Amendment 4 
22-Jan-2024 
Tisotumab vedotin 
Seagen Inc. – Confidential 
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Section # and Name 
Description of Change 
Brief Rationale 
8.2.6 Clinical Laboratory 
Assessments 
Pregnancy test results no longer excepted 
from reporting to central laboratory  
Consistency of collection of results 
for all clinical laboratory testing 
10.7 Recommended Dose 
Modifications for 
Chemotherapy Arm 
Source citations added for recommended 
dose modifications 
Compliance with best practices for 
study protocols 
 
Amendment 2  
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union 
because it either significantly impacts the safety or physical/mental integrity of participants or 
the scientific value of the study. 
Protocol Amendment Summary of Changes Table: Amendment 2  
 
Section # and Name 
Description of Change 
Brief Rationale 
Title page 
Logo and study numbers for cooperative 
groups ENGOT and GOG added  
Addition to reflect the cooperative 
groups on the study 
Title page 
 added as Seagen medical 
monitor. 
 removed as Seagen 
medical monitor 
New medical monitor assigned to 
the study 
1.3 Schedule of Activities  
Randomization window changed from 
within ≤3 days of C1D1 to within ≤7 days 
Time window for randomization 
extended to better accommodate 
premedication and dosing 
schedules for investigator’s choice 
chemotherapy options 
1.3 Schedule of Activities  
Steroid eye drops are to be administered on 
Day -1 of each cycle 
Clarification 
1.3 Schedule of Activities 
Row added for Patient Eye Drop Diary 
Clarification 
1.3 Schedule of Activities  
Predose sampling for biomarker collection 
specified to be within 24 hours prior to 
dosing 
Clarification 
1.3 Schedule of Activities  
Plasma protein and plasma DNA/RNA 
biomarker collection updated to include 
Cycles 20 and 24 
Additional assessments to extend 
collection of biomarkers 
1.3 Schedule of Activities  
Separated footnotes for optional biopsy 
collected at time of radiographic disease 
progression and biopsy collected per 
standard of care while the participant is on 
study  
Clarification 
1.3 Schedule of Activities  
Premedication for chemotherapy at C1D1 
removed  
Clarification 

Protocol 
 
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Study SGNTV-003 
Clinical Protocol Amendment 4 
22-Jan-2024 
Tisotumab vedotin 
Seagen Inc. – Confidential 
Page 5 of 115 
Section # and Name 
Description of Change 
Brief Rationale 
2.3 Benefit/Risk 
Assessment 
Existing information referenced for benefits 
and risks of treatment with tisotumab 
vedotin. Additional statements added on 
known and potential risks 
Provision of additional information 
in the Benefit/Risk Assessment 
section in response to feedback 
from global regulatory authority 
4.1 Overall Design 
9.2 Sample Size 
Determination 
Verbiage added to denote that no crossover 
is allowed in the study 
Clarification 
4.4.2 Study Termination 
Verbiage added to define conditions for 
termination of the entire trial 
Clarification as requested by global 
health authority 
4.4.2 Study Termination 
Verbiage added to clarify whether or not 
there is access to the drug once the study is 
completed 
Clarification as requested by global 
health authority 
5.1 Inclusion Criteria 
1.1 Synopsis 
Inclusion criterion for minimum age 
modified 
Changed to allow for regional 
differences in age of consent 
5.1 Inclusion Criteria 
Calculated eGFR (MDRD formula) 
threshold changed from >50 
mL/min/1.73m2 to ≥50 mL/min/1.73m2 
Clarification 
5.1 Inclusion Criteria 
Hematological status assessment timing 
after transfusion changed from at least 2 
weeks after transfusion to at least 1 week 
after transfusion 
Timing of hematological status 
after transfusion with blood 
products and/or growth factor 
support reduced to reduce barriers 
to enrollment 
5.1 Inclusion Criteria 
Inclusion criterion 12 removed 
This criterion is no longer included 
in late stage Seagen protocols. 
Biopsy tissue procurement is still 
required as part of screening 
procedures 
6.6.2.2 Other AEs for 
Tisotumab Vedotin 
Section 7.1.1 Summary of 
Safety Stopping Rules 
Permanent discontinuation of tisotumab 
vedotin added as a dose modification rule 
for bleeding events and elevated liver 
parameters of grade 4 severity 
Changes requested by global health 
authority 
8.2.1 Tumor Imaging 
Verbiage added to clarify that tumor images 
may be collected for a potential blinded 
independent central review  
Clarification 
8.2.1.1 Baseline Imaging 
Assessments 
Verbiage “if clinically suspected” added for 
whole-body bone scan imaging 
Clarification  
8.3.6 Clinical Laboratory 
Assessments Table 9 
HbA1C removed from table of laboratory 
assessments 
Correction 
8.7.3 Tumor Tissue Sample 
Collection 
Verbiage ‘At screening’ added to clarify 
timing and that biopsy collected as per 
standard of care was performed if 
participant provides consent 
Clarification 
9.5.6 Exploratory Analyses 
Verbiage added to clarify that ADA 
concentration will not be summarized, only 
ADA incidence 
Correction 

Protocol 
 
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Study SGNTV-003 
Clinical Protocol Amendment 4 
22-Jan-2024 
Tisotumab vedotin 
Seagen Inc. – Confidential 
Page 6 of 115 
Section # and Name 
Description of Change 
Brief Rationale 
9.6.2 Safety Laboratory 
Tests, Vital Signs, and ECG 
Parameters 
Verbiage added to clarify that 12-lead ECG 
will not be summarized 
Correction 
9.6.1 AEs 
Verbiage added to clarify which TEAE 
analyses will be summarized 
Correction 
 
Amendment 3  
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union 
because it either significantly impacts the safety or physical/mental integrity of participants or 
the scientific value of the study. 
Protocol Amendment Summary of Changes Table: Amendment 3  
 
Section # and Name 
Description of Change 
Brief Rationale 
Title Page 
 added as Seagen medical 
monitor. 
 removed as Seagen 
medical monitor 
New medical monitor assigned to 
the study 
1.1. Synopsis  
4.1. Overall Design  
7.1. Discontinuation of Study 
Treatment  
8.2.1.2. Post baseline 
imaging assessments 
Verbiage added throughout for continued 
imaging to be “until evidence of 
radiographic disease progression or until 
the start of new anti-cancer treatment, 
withdrawal of consent, death, or the end of 
the study, whichever occurs first”. 
Clarification 
1.3 Schedule of Activities 
eGFR to be collected within 7 days of 
C1D1 instead of within 28 days in Tables 1 
and 3 
Correction 
1.3 Schedule of Activities 
Laboratory assessments (Hematology, 
Biochemistry, and Coagulation factors) and 
Pregnancy test moved up in Tables 1 and 3 
Clarification for better visibility 
1.3 Schedule of Activities 
“After Cycle 1, pre-dose laboratory 
procedures can be conducted ≤72 hours 
prior to dosing” specified to be applicable 
to all laboratory assessments in Tables 1 
and 3 
Clarification 
1.3 Schedule of Activities 
Radiology assessments to be performed at 
EOT, with exception for previous tumor 
imaging obtained within 4 weeks  
Clarification 
1.3 Schedule of Activities 
Health-related quality of life assessments 
to be collected “< 7 days” of C1D1 instead 
of “≤ 7 days”. 
Correction 
1.3 Schedule of Activities 
Eye drops administration specified to be 
‘prior to dosing’ 
Clarification 

Protocol 
 
SGNTV-003 
Study SGNTV-003 
Clinical Protocol Amendment 4 
22-Jan-2024 
Tisotumab vedotin 
Seagen Inc. – Confidential 
Page 7 of 115 
Section # and Name 
Description of Change 
Brief Rationale 
1.3 Schedule of Activities 
“Reference to Table 2 for detailed time 
points” for Anti-drug antibodies 
(immunogenicity) and Pharmacokinetic 
sampling rows in Tables 1 and 3 extended 
to apply to EOT visit 
Clarification 
1.3 Schedule of Activities 
Plasma protein biomarkers removed 
Change due to program-wide 
recommendations 
1.3 Schedule of Activities 
Footnote for HRQOL assessments 
corrected for the control arm in Table 3 
Correction 
1.3 Schedule of Activities 
Ocular assessments and eye examination 
are not to be performed at unscheduled 
visits for the control arm, as updated in 
Table 3 
Correction 
2.1.1. Unmet Need 
2.2.1. 
Overview of the 
Disease 
Details of KEYNOTE-826 study and anti-
PD-(L)1 therapy added 
Updates to reflect changing 
treatment landscape 
4.3. Justification for Dose  
6.1.2 Chemotherapy Control 
Arm  
10.7.1 Recommended Dose 
Modifications for Topotecan 
10.7.2 Recommended Dose 
Modifications for Irinotecan 
Clarified starting dose for topotecan and 
irinotecan 
Change to provide more flexibility 
to physicians in treatment of trial 
participants 
5.1 Inclusion Criteria 
and Synopsis 
Prior anti-PD-(L)1 therapy added 
Changes to reflect updated 
treatment landscape 
5.2 Exclusion Criteria 
Exclusion #6 language revised to focus on 
prognosis/survival 
Clarification 
5.2 Exclusion Criteria 
Exclusion #12 amended to include 
exceptions for latent or controlled HIV 
infection. 
Clarification 
5.4 Screen Failures 
Sponsor approval of rescreening removed. 
Change to remove barriers to 
enrolment that did not affect 
patient safety 
5.4 Screen Failures 
Clarified that biopsy is no longer required 
for eligibility as per Amendment 2. 
Clarification 
6.1.1. Tisotumab Vedotin 
Arm 
Physical Description updated 
Changes to match updates to the 
Pharmacy Manual 
6.3.1 Treatment 
Randomization 
Heading removed to simplify section 
Clarification 
6.5.1.1. Tisotumab Vedotin 
Arm 
Premedication for Tisotumab 
Vedotin 
“as needed” removed for self-
administration of lubricating eye drops 
Clarification 

Protocol 
 
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Clinical Protocol Amendment 4 
22-Jan-2024 
Tisotumab vedotin 
Seagen Inc. – Confidential 
Page 8 of 115 
Section # and Name 
Description of Change 
Brief Rationale 
6.5.3. Prohibited 
Concomitant Therapy 
Herbal medicines removed 
Change to allow enrollment of 
participants in regions where 
herbal medicines are commonly 
used 
7.1.2.2. Survival Follow-up 
Specified follow-up to start from date of 
EOT visit for participants who are taken 
off treatment before receiving any study 
drug 
Clarification 
8.4.2. Adverse Event 
Reporting  
Safety reporting period for all AEs 
amended to 30 days after the last study 
treatment 
Clarification 
8.4.6. Pregnancy 
Follow-up duration extended to up to 6 
months of age for the child 
Change to allow for longer follow-
up in cases of pregnancy in 
accordance with regulatory agency 
feedback 
8.7. Biomarkers 
Clarified and simplified biomarker 
language according to current standard 
biomarker group language. 
Clarification 
(8.7.2) Biomarker 
Assessments in Blood 
Samples 
Circulating tissue factor assay removed 
from the biomarker analysis and section 
removed 
Assay was deemed not informative 
8.7.2 Tumor Tissue Sample 
Collection 
Verbiage added to clarify that the most 
recent archival tumor biopsy is to be 
submitted for the purposes of screening and 
not submitted in the case of a screen failure 
Clarification 
 
 
 

Protocol 
 
SGNTV-003 
Study SGNTV-003 
Clinical Protocol Amendment 4 
22-Jan-2024 
Tisotumab vedotin 
Seagen Inc. – Confidential 
Page 9 of 115 
 
Amendment 4  
This amendment is considered to be non-substantial based on the criteria set forth in Article 2 of 
Regulation 536/2014 of the European Parliament and the Council of the European Union 
because it neither significantly impacts the safety or physical/mental integrity of participants nor 
the scientific value of the study. 
 
Overall Rationale for the Amendment  
The amendment was made to align with EU CTIS/CTR requirements.  
Protocol Amendment Summary of Changes Table: Amendment 4  
 
Section # and 
Name 
Description of Change 
Substantial Change 
Brief Rationale 
Title Page, page 1 
Added EU Trial Number 
No 
To align with EU 
CTIS/CTR requirements 
Title Page, page 1 
Updated Sponsor information to 
include footnote: “Please note 
that as of 14-Dec-2023, Seagen 
Inc. became a part of Pfizer 
Inc.”  
No 
Clarification 
Title Page, page 2 
 added as medical 
monitor. 
 removed 
as medical monitor 
No 
New medical monitor 
assigned to the study 
 
 

Protocol 
 
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Clinical Protocol Amendment 4 
22-Jan-2024 
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Page 10 of 115 
TABLE OF CONTENTS 
TITLE PAGE ................................................................................................................................................................. 1 
DOCUMENT HISTORY AND SUMMARY OF CHANGES ..................................................................................... 3 
Amendment 1 ........................................................................................................................................................ 3 
Protocol Amendment Summary of Changes Table: Amendment 1 ...................................................................... 3 
Amendment 2 ........................................................................................................................................................ 4 
Protocol Amendment Summary of Changes Table: Amendment 2 ...................................................................... 4 
Amendment 3 ........................................................................................................................................................ 6 
Protocol Amendment Summary of Changes Table: Amendment 3 ...................................................................... 6 
Amendment 4 ........................................................................................................................................................ 9 
Protocol Amendment Summary of Changes Table: Amendment 4 ...................................................................... 9 
1. 
PROTOCOL SUMMARY ............................................................................................................................... 14 
1.1. 
Synopsis ................................................................................................................................................ 14 
1.2. 
Schema.................................................................................................................................................. 17 
1.3. 
Schedule of Activities (SoA) ................................................................................................................ 17 
2. 
INTRODUCTION............................................................................................................................................ 36 
2.1. 
Study Rationale ..................................................................................................................................... 36 
2.1.1. 
Unmet Need ......................................................................................................................... 36 
2.1.2. 
Study Population ................................................................................................................. 37 
2.1.3. 
Control Arm ......................................................................................................................... 37 
2.2. 
Background ........................................................................................................................................... 37 
2.2.1. 
Overview of the Disease ...................................................................................................... 37 
2.2.2. 
Introduction to the Investigational Medicinal Product ........................................................ 38 
2.2.3. 
Summary of Clinical Trials ................................................................................................. 39 
2.3. 
Benefit/Risk Assessment ...................................................................................................................... 40 
3. 
OBJECTIVES AND ENDPOINTS.................................................................................................................. 42 
4. 
STUDY DESIGN ............................................................................................................................................. 43 
4.1. 
Overall Design ...................................................................................................................................... 43 
4.2. 
Scientific Rationale for Study Design ................................................................................................... 43 
4.3. 
Justification for Dose ............................................................................................................................ 44 
4.4. 
End of Study Definition ........................................................................................................................ 44 
4.4.1. 
End of Study Definition ....................................................................................................... 44 
4.4.2. 
Study Termination ............................................................................................................... 44 
5. 
STUDY POPULATION .................................................................................................................................. 46 
5.1. 
Inclusion Criteria .................................................................................................................................. 46 
5.2. 
Exclusion Criteria ................................................................................................................................. 48 
5.3. 
Lifestyle Considerations ....................................................................................................................... 50 
5.4. 
Screen Failures...................................................................................................................................... 50 
6. 
STUDY INTERVENTION .............................................................................................................................. 52 
6.1. 
Study Intervention(s) Administered ...................................................................................................... 52 
6.1.1. 
Tisotumab Vedotin Arm ...................................................................................................... 52 
6.1.2. 
Chemotherapy Control Arm ................................................................................................ 53 
6.2. 
Preparation/Handling/Storage/Accountability ...................................................................................... 53 
6.2.1. 
Tisotumab Vedotin .............................................................................................................. 53 
6.2.2. 
Chemotherapy Control Arm ................................................................................................ 54 
6.2.3. 
Drug Accountability ............................................................................................................ 54 
6.2.3.1. 
Technical Complaint Handling ................................................................................ 54 
6.3. 
Measures to Minimize Bias: Randomization and Blinding .................................................................. 55 
6.4. 
Study Intervention Compliance ............................................................................................................ 55 
6.5. 
Concomitant Therapy ........................................................................................................................... 55 
6.5.1. 
Premedications and Supportive Care ................................................................................... 55 
6.5.1.1. 
Tisotumab Vedotin Arm........................................................................................... 55 
6.5.1.2. 
Chemotherapy Control Arm ..................................................................................... 56 
6.5.2. 
Permitted Concomitant Medications and Therapies ............................................................ 57 
6.5.2.1. 
Permitted Concomitant Medications and Therapies for Tisotumab Vedotin Arm ... 57 

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6.5.2.2. 
Permitted Concomitant Therapy for Tisotumab Vedotin Arm Requiring Caution or 
Action ....................................................................................................................... 57 
6.5.2.3. 
Permitted Concomitant Therapy for the Chemotherapy Arm .................................. 57 
6.5.3. 
Prohibited Concomitant Therapy ......................................................................................... 57 
6.6. 
Dose Modification ................................................................................................................................ 58 
6.6.1. 
Dose Modifications for Tisotumab Vedotin ........................................................................ 58 
6.6.1.1. 
Dose Reduction for Tisotumab Vedotin ................................................................... 58 
6.6.1.2. 
Dose Delay for Tisotumab Vedotin .......................................................................... 59 
6.6.2. 
Dose Modification Guidelines and Preventive Measures for Specific AEs Observed with 
Tisotumab Vedotin .............................................................................................................. 59 
6.6.2.1. 
Ocular AEs ............................................................................................................... 59 
6.6.2.2. 
Other AEs for Tisotumab Vedotin ........................................................................... 63 
6.6.3. 
Dose Modifications for the Chemotherapy Control Arm .................................................... 65 
6.7. 
Intervention after the End of the Study ................................................................................................. 65 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................................................ 66 
7.1. 
Discontinuation of Study Treatment ..................................................................................................... 66 
7.1.1. 
Summary of Safety Stopping Rules ..................................................................................... 66 
7.1.2. 
End of Treatment Visit ........................................................................................................ 67 
7.1.2.1. 
Post-Study Treatment Anti-Cancer Therapy Status ................................................. 67 
7.1.2.2. 
Survival Follow-up................................................................................................... 67 
7.2. 
Participant Discontinuation/Withdrawal from the Study ...................................................................... 68 
7.2.1. 
Follow-up for Safety Evaluations ........................................................................................ 68 
7.3. 
Lost to Follow up .................................................................................................................................. 68 
8. 
STUDY ASSESSMENTS AND PROCEDURES ........................................................................................... 69 
8.1. 
Demography and Baseline Assessments ............................................................................................... 69 
8.1.1. 
Demographics ...................................................................................................................... 69 
8.1.2. 
Diagnosis and Disease Status .............................................................................................. 69 
8.1.3. 
Medical History ................................................................................................................... 69 
8.1.4. 
Concomitant Medication ..................................................................................................... 69 
8.1.5. 
Prior Cancer Therapy and Surgery ...................................................................................... 70 
8.2. 
Efficacy Assessments ........................................................................................................................... 70 
8.2.1. 
Tumor Imaging .................................................................................................................... 70 
8.2.1.1. 
Baseline Imaging Assessments ................................................................................ 70 
8.2.1.2. 
Post baseline imaging assessments........................................................................... 72 
8.2.2. 
Survival Status ..................................................................................................................... 73 
8.3. 
Safety Assessments ............................................................................................................................... 73 
8.3.1. 
Physical Examination .......................................................................................................... 73 
8.3.2. 
Vital Signs ........................................................................................................................... 73 
8.3.3. 
Electrocardiograms .............................................................................................................. 73 
8.3.4. 
ECOG Performance Status .................................................................................................. 74 
8.3.5. 
Eye Examination and Ocular Assessment ........................................................................... 74 
8.3.6. 
Clinical Laboratory Assessments......................................................................................... 74 
8.4. 
Adverse Events and Serious Adverse Events ....................................................................................... 76 
8.4.1. 
Adverse Event Definitions ................................................................................................... 76 
8.4.1.1. 
Definition of Adverse Event .................................................................................... 76 
8.4.1.2. 
Definition of Serious Adverse Event ........................................................................ 76 
8.4.1.3. 
Definition of AEs of Special Interest for Tisotumab Vedotin .................................. 77 
8.4.2. 
Adverse Event Reporting ..................................................................................................... 77 
8.4.3. 
Follow-up of Adverse Events and Serious Adverse Events ................................................ 78 
8.4.4. 
Diagnosis ............................................................................................................................. 78 
8.4.5. 
Suspected Unexpected Serious Adverse Reactions ............................................................. 78 
8.4.6. 
Pregnancy ............................................................................................................................ 78 
8.4.7. 
Pre-existing Condition ......................................................................................................... 79 
8.4.8. 
Disease Progression or Death .............................................................................................. 79 
8.4.9. 
Unrelated Procedures ........................................................................................................... 79 

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8.4.10. 
Laboratory Test Abnormalities ............................................................................................ 79 
8.4.11. 
Information About Infusion-Related Reactions ................................................................... 80 
8.5. 
Treatment of Overdose ......................................................................................................................... 80 
8.5.1. 
Overdose and Medication Errors ......................................................................................... 80 
8.6. 
Pharmacokinetics .................................................................................................................................. 80 
8.7. 
Biomarkers ............................................................................................................................................ 81 
8.7.1. 
Biomarker Assessments in Blood and Tumor Samples ....................................................... 81 
8.7.2. 
Tumor Tissue Sample Collection ........................................................................................ 81 
8.7.3. 
DNA/RNA Research ........................................................................................................... 82 
8.7.4. 
Patient Reported Outcomes ................................................................................................. 82 
8.8. 
Immunogenicity Assessments ............................................................................................................... 83 
8.8.1. 
Evaluations .......................................................................................................................... 83 
8.8.2. 
Immunogenicity Assessments ............................................................................................. 83 
9. 
STATISTICAL CONSIDERATIONS ............................................................................................................. 84 
9.1. 
Statistical Hypotheses ........................................................................................................................... 84 
9.2. 
Sample Size Determination .................................................................................................................. 84 
9.3. 
Populations for Analyses ...................................................................................................................... 84 
9.4. 
General Considerations ......................................................................................................................... 85 
9.4.1. 
Responsibility for Analyses/In-house Blinding ................................................................... 85 
9.5. 
Efficacy Analyses ................................................................................................................................. 85 
9.5.1. 
Overall Survival ................................................................................................................... 85 
9.5.2. 
Progression-Free Survival Assessed per Investigator .......................................................... 86 
9.5.3. 
Confirmed Objective Response Rate as Assessed by Investigator ...................................... 86 
9.5.4. 
Health-related Quality of Life (HRQOL) ............................................................................ 86 
9.5.5. 
Duration of Response and Time to Response ...................................................................... 86 
9.5.6. 
Exploratory Analyses .......................................................................................................... 86 
9.5.7. 
Testing Strategy ................................................................................................................... 86 
9.6. 
Safety Analyses .................................................................................................................................... 87 
9.6.1. 
AEs ...................................................................................................................................... 87 
9.6.2. 
Safety Laboratory Tests, Vital Signs, and ECG Parameters ................................................ 88 
9.7. 
Interim Analyses ................................................................................................................................... 88 
9.8. 
Trial Governance and Oversight ........................................................................................................... 88 
9.8.1. 
Independent Data Monitoring Committee (IDMC) ............................................................. 88 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ................................... 89 
10.1. 
APPENDIX 1: Regulatory, Ethical, and Study Oversight Considerations ........................................... 89 
10.1.1. 
Protocol Amendments ......................................................................................................... 89 
10.1.2. 
Regulatory Approval/Notification ....................................................................................... 89 
10.1.3. 
Participant Identification, Enrollment, and Screening Logs ................................................ 89 
10.1.3.1. 
Participant Identification Card ................................................................................. 89 
10.1.4. 
Ethics ................................................................................................................................... 90 
10.1.4.1. 
Trial-Specific Design Considerations ...................................................................... 90 
10.1.4.2. 
Regulatory Ethics Compliance ................................................................................. 90 
10.1.4.3. 
Return of Exploratory Research Data to Participants and Investigators .................. 91 
10.1.5. 
Biospecimen Repository ...................................................................................................... 91 
10.1.6. 
Regulatory and Ethical Considerations/Statement of Compliance ...................................... 91 
10.1.7. 
Financial Disclosure ............................................................................................................ 92 
10.1.8. 
Clinical Trial Agreement ..................................................................................................... 92 
10.1.9. 
Investigator Information ...................................................................................................... 92 
10.1.10. 
Informed Consent Process ................................................................................................... 92 
10.1.11. 
Data Protection .................................................................................................................... 93 
10.1.11.1. Study Documentation, Privacy and Records Retention............................................ 93 
10.1.12. 
Data Quality Assurance ....................................................................................................... 94 
10.1.12.1. Monitoring ............................................................................................................... 94 
10.1.13. 
Source Documents ............................................................................................................... 94 
10.1.14. 
Study and Site Start and Closure ......................................................................................... 94 
10.1.15. 
Publication Policy ................................................................................................................ 95 

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10.1.16. 
Registration of Clinical Trials and Disclosure of Results .................................................... 95 
10.2. 
APPENDIX 2: Clinical Laboratory Tests ............................................................................................. 96 
10.3. 
APPENDIX 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-up, 
and Reporting........................................................................................................................................ 97 
10.4. 
APPENDIX 4: Definition of Reproductive Potential and Guidance on Contraception ........................ 98 
10.5. 
APPENDIX 5: Genetics...................................................................................................................... 100 
10.6. 
APPENDIX 6: Liver Safety: Potential Drug-Induced Liver Injury .................................................... 101 
10.7. 
APPENDIX 7: Dose Modifications for the Chemotherapy Arm ........................................................ 102 
10.7.1. 
Recommended Dose Modifications for Topotecan ........................................................... 103 
10.7.2. 
Recommended Dose Modifications for Irinotecan ............................................................ 104 
10.7.3. 
Recommended Dose Modifications for Gemcitabine ........................................................ 106 
10.7.4. 
Recommended Dose Modifications for Vinorelbine ......................................................... 107 
10.7.5. 
Recommended Dose Modifications for Single Agent Pemetrexed .................................... 108 
10.8. 
APPENDIX 8: Investigator Signature Page........................................................................................ 109 
10.9. 
APPENDIX 9: Abbreviations ............................................................................................................. 110 
11. 
REFERENCES ............................................................................................................................................... 113 
 
LIST OF TABLES  
Table 1: 
Visit Assessment Schedule for the Tisotumab Vedotin Arm ................................................................ 18 
Table 2: 
Pharmacokinetic and Anti-drug Antibodies Sampling for the Tisotumab Vedotin Arm ...................... 27 
Table 3: 
Visit Assessment Schedule for the Control Arm (Chemotherapy) ....................................................... 28 
Table 4: 
Objectives and Endpoints ..................................................................................................................... 42 
Table 5: 
Clinical Outcomes in the Second Line and Beyond.............................................................................. 44 
Table 6: 
Tisotumab Vedotin Dose Modification Scheme ................................................................................... 58 
Table 7: 
Imaging Assessment Collection Plan .................................................................................................... 72 
Table 8: 
ECOG Performance Status ................................................................................................................... 74 
Table 9: 
Laboratory Assessments ....................................................................................................................... 75 
Table 10: 
Acceptable Methods of Contraception .................................................................................................. 99 
 
LIST OF FIGURES  
Figure 1: 
Study Design ......................................................................................................................................... 17 
 

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1. 
PROTOCOL SUMMARY  
1.1. 
Synopsis  
Protocol Title: 
A Randomized, Open-Label, Phase 3 Trial of Tisotumab Vedotin vs 
Investigator’s Choice Chemotherapy in Second- or Third-Line Recurrent or Metastatic Cervical 
Cancer 
Short Title: 
Phase 3 Trial of Tisotumab Vedotin vs Chemotherapy in Recurrent or 
Metastatic Cervical Cancer 
Rationale: 
Tisotumab vedotin is an antibody-drug conjugate (ADC) targeting tissue 
factor (TF). Safety and efficacy data demonstrate the potential for tisotumab vedotin to 
substantially improve clinical outcomes with a manageable safety profile in participants with 
recurrent/metastatic cervical cancer (r/mCC) who have received 1 or 2 prior lines of systemic 
therapy. The purpose of this trial is to evaluate the efficacy of tisotumab vedotin compared to 
investigator’s choice of chemotherapy in participants with r/mCC who have received 1 or 2 prior 
lines of systemic therapy for their recurrent or metastatic disease. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
 
● Demonstrate improvement in clinical efficacy of 
tisotumab vedotin compared to chemotherapy in 
participants with second- or third-line (2L-3L) 
cervical cancer 
● Overall survival (OS) 
Secondary 
 
● Assess improvement in clinical efficacy of tisotumab 
vedotin compared to chemotherapy in participants 
with 2L-3L cervical cancer 
● Progression-free survival (PFS) based on Response 
Evaluation Criteria in Solid Tumors (RECIST) v1.1 
as assessed by the investigator 
● Demonstrate improvement in antitumor activity of 
tisotumab vedotin compared to chemotherapy in 
participants with 2L-3L cervical cancer 
● Confirmed objective response rate (ORR) based on 
RECIST v1.1 as assessed by the investigator 
● Characterize the antitumor response of tisotumab 
vedotin and chemotherapy in participants with 2L-3L 
cervical cancer 
● Time-to-response (TTR) as assessed by the 
investigator 
● Duration of response (DOR) as assessed by the 
investigator 
● Evaluate the safety and tolerability of tisotumab 
vedotin 
● Incidence of adverse events (AEs) 
● Assess health-related quality of life (HRQOL) 
● EQ-5D-5L index 
● EQ-5D visual analog scale (VAS) 
● EORTC-QLQ-C30 
● EORTC-QLQ-CX24 
Exploratory 
 
● Investigate the relationship between tumor TF 
expression and response to tisotumab vedotin 
● Tumor TF expression (via immunohistochemistry 
[IHC] or RNA) in relation to efficacy endpoints 
● Assess biomarkers and their association with disease, 
mechanisms of resistance, and/or response to therapy 
● Baseline characteristics and changes from baseline of 
biomarkers from peripheral blood and/or formalin-

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Objectives 
Endpoints 
fixed paraffin-embedded (FFPE) tumor tissue in 
relation to efficacy endpoints 
● Evaluate pharmacokinetics (PK) and 
immunogenicity of tisotumab vedotin 
● PK concentrations and anti-drug antibodies (ADAs) 
associated with tisotumab vedotin 
Overall Design: 
This is an open-label, randomized (1:1), global, phase 3 trial of tisotumab vedotin versus 
investigator’s choice of chemotherapy in participants with r/mCC who have received 1 or 2 prior 
lines of systemic therapy for their recurrent or metastatic disease. Eligible participants will be 
randomized to either tisotumab vedotin 2.0 mg/kg every 3 weeks (Q3W) or investigator’s choice 
of chemotherapy (as noted in the “other study treatment” section). Randomization will be 
stratified by Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1), prior 
bevacizumab administration (yes vs. no), region (US, EU, Other), and prior anti-programmed 
cell death protein 1 or anti-programmed cell death ligand 1 (anti-PD-[L]1) administration 
(yes vs. no). Imaging will be obtained every 6 weeks (42 days ±7 days) for the first 30 weeks and 
then every 12 weeks (84 days ±7 days) thereafter, calculated from Cycle 1 Day 1 (C1D1) of 
treatment administration. Imaging must continue until evidence of radiographic disease 
progression per RECIST v1.1 as assessed by investigator or until the start of new anti-cancer 
treatment, withdrawal of consent, death, or the end of the study, whichever occurs first. Survival 
status will be assessed every 60 days (±7 days) beginning from the day of the last dose of study 
treatment, or more frequently around the time of a database lock. 
An independent data monitoring committee (IDMC), consisting of members who are external 
and independent of the sponsor study team, will be formed to monitor the safety of participants 
in this study on a periodic basis, review safety and efficacy data from this study as per planned 
analyses, and make recommendations to the sponsor. 
Key Inclusion Criteria: 
• Age ≥18 years, or considered an adult by local regulations, at time of consent. 
• Has recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or 
adenosquamous histology, and: 
• Has experienced disease progression during or after treatment with a standard of care 
systemic chemotherapy doublet, or platinum-based therapy (if eligible), defined as 
either: 
− paclitaxel+cisplatin+bevacizumab+ anti-PD-(L)1 agent, or 
− paclitaxel+carboplatin+bevacizumab+ anti-PD-(L)1 agent, or 
− paclitaxel+topotecan/nogitecan+bevacizumab+ anti-PD-(L)1 agent 
NOTE: only in cases where bevacizumab and/or anti-PD-(L)1 agent is not a standard 
of care therapy or the participant was ineligible for such treatment according to local 
standards, prior treatment with bevacizumab and/or anti-PD-(L)1 agent is not 
required. 

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• Has received 1 or 2 prior systemic therapy regimens for recurrent and/or metastatic 
cervical cancer. Chemotherapy administered in the adjuvant or neoadjuvant setting, or 
in combination with radiation therapy, should not be counted as a systemic therapy 
regimen. Single agent therapy with an anti-PD(L)1 agent for r/mCC cancer should be 
counted. 
• Measurable disease according to RECIST v1.1 as assessed by the investigator. 
• Has ECOG performance status of 0 or 1 prior to randomization. 
• Has life expectancy of at least 3 months. 
Key Exclusion Criteria: 
• Has primary neuroendocrine, lymphoid, sarcomatoid, or other histologies not 
mentioned as part of the inclusion criteria above.  
• Has clinically significant bleeding issues or risks. This includes known past or current 
coagulation defects leading to an increased risk of bleeding; diffuse alveolar 
hemorrhage from vasculitis; known bleeding diathesis; ongoing major bleeding; 
trauma with increased risk of life-threatening bleeding or history of severe head 
trauma or intracranial surgery within 8 weeks of trial entry. 
• Has any history of intracerebral arteriovenous malformation, cerebral aneurysm, or 
stroke (transient ischemic attack >1 month prior to screening is allowed). 
• Active ocular surface disease or a history of cicatricial conjunctivitis or inflammatory 
conditions that predispose to cicatrizing conjunctivitis (eg, Wagner syndrome, atopic 
keratoconjunctivitis, autoimmune disease affecting the eyes), ocular Stevens-Johnson 
syndrome or toxic epidermal necrolysis, mucus pemphigoid, and participants with 
penetrating ocular transplants. Cataracts alone is not an exclusion criterion. 
• Major surgery within 4 weeks or minor surgery within 7 days prior to the first study 
treatment administration. 
• Peripheral neuropathy ≥grade 2. 
• Any prior treatment with monomethyl auristatin E (MMAE)-containing drugs. 
Number of Participants: Approximately 482 participants will be randomized in the study. 
Intervention Groups and Duration: 
Study Drug: Tisotumab vedotin 2.0 mg/kg Q3W 
Comparator(s): Investigator’s choice, one of the following: 
• topotecan 1 or 1.25 mg/m2 intravenous (IV) on Days 1 to 5, every 21 days 
• vinorelbine 30 mg/m2 IV on Days 1 and 8, every 21 days 
• gemcitabine 1000 mg/m2 IV on Days 1 and 8, every 21 days 
• irinotecan 100 or 125 mg/m2 IV weekly for 28 days, every 42 days 
• pemetrexed 500mg/m2 IV on Day 1 every 21 days 

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Dose Modifications: An individual’s dose may be modified based upon treatment-emergent 
adverse events. 
Data Monitoring Committee: Yes 
1.2. 
Schema  
The design of the study is shown in Figure 1. 
Figure 1: 
Study Design  
 
1.3. 
Schedule of Activities (SoA)  
Table 1 lists all the assessments in the tisotumab vedotin arm and indicates the visits to be 
performed and the associated timing. In addition to the fixed visits, it may be necessary to 
perform some of the assessments at unscheduled time points if deemed clinically necessary by 
the investigator. Table 2 shows the timing of the PK and ADA assessments in the tisotumab 
vedotin arm. Table 3 shows the timing of the assessments in the control arm (chemotherapy). 
 

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a. 
Cycle duration and administration days vary. Refer to Section 6.1.2. In addition to the scheduled assessments, the frequency of AE collection, vital signs, and 
laboratory assessments should be guided by local label and guidelines for topotecan, vinorelbine, gemcitabine, irinotecan, and pemetrexed. 
b. If screening assessment is performed within 1 day of C1D1, this test does not need to be repeated on C1D1. 
c. 
Pregnancy tests (serum or urine) are to be repeated monthly for 6 months after the last dose of investigator’s choice chemotherapy.  
d. EORTC-QLQ-CX24 should be performed on D1 of every cycle for the first 20 cycles only. In participants who receive irinotecan, EORTC-QLQ-CX24 
should be performed on D1 for the first 10 cycles only. 
e. 
EQ-5D-5L and EQ-5D VAS only. 
f. 
For participants without significant toxicity during the first 21-day cycle of topotecan, subsequent cycles may be increased to 1.25 mg/m2 IV × 5 days, every 
21 days. 
g. For participants without significant toxicity during the first 42-day cycle of irinotecan, subsequent cycles may be increased to 125 mg/m2 IV weekly × 4, 
followed by 14 days off treatment. 
h. In addition to the required baseline biopsy, an optional fresh biopsy collected at time of radiographic disease progression may be provided for biomarker 
analyses, if clinically feasible and if the participant provides consent for this procedure.  
i. 
If a tumor biopsy is collected per standard of care while the participant is on study (until treatment discontinuation), the FFPE block or unstained slides may 
be provided for biomarker analyses, if the participant provides consent for this procedure. 

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2. 
INTRODUCTION  
2.1. 
Study Rationale  
High, differential levels of expression of tisotumab vedotin’s target, tissue factor (TF), have been 
observed on the membranes of neoplastic cells as well as on tumor-associated endothelium in 
multiple cancers, including gynecological cancers of the cervix. Expression of TF on tumor cells 
has been associated with negative overall survival (OS) or disease-free survival as described in 
several indications. In preclinical studies, tisotumab vedotin treatment resulted in potent and 
long-lasting tumor regression in TF-expressing xenograft models derived from a variety of solid 
cancers, including patient-derived xenograft models with heterogeneous TF expression. 
Tisotumab vedotin showed evidence of activity in 101 participants with second and third-line 
(3L) recurrent or metastatic cervical cancer (r/mCC) in the GCT1015-04 pivotal phase 2 trial. In 
the current study, tisotumab vedotin will be further examined through a randomized study design 
to compare against single agent chemotherapy in this patient population. Patients with r/mCC 
have significant unmet medical need and therefore new therapies are needed. 
2.1.1. 
Unmet Need  
Women with cervical cancer who have progressed on first-line (1L) therapy comprise a 
population of high unmet medical need, and the development of new therapies is crucial to 
address this devastating disease. This study will enroll participants with r/mCC who have 
experienced disease progression during or after treatment with doublet chemotherapy and 
bevacizumab, if deemed appropriate. 
Mortality rate is high for patients with r/mCC. While patients with persistent, recurrent, or 
metastatic carcinoma of the cervix may receive the standard of care 1L treatment of bevacizumab 
and/or therapies targeting anti-programmed cell death protein 1 or anti-programmed cell death 
ligand 1 (anti-PD-[L]1) in combination with paclitaxel+cisplatin/carboplatin or 
paclitaxel+topotecan, these patients invariably progress. In addition, restrictions in the 
bevacizumab label and limited global availability of anti-PD-(L)1 agents suggest that a 
proportion of 1L patients are not eligible to receive this therapy, and thus, the standard of care 
for these patients is doublet chemotherapy. 
In a double-blind, phase 3 trial with 1L pembrolizumab (KEYNOTE-826) in combination with 
standard of care treatment, progression-free survival (PFS) and OS were significantly longer 
with pembrolizumab than with placebo among patients with persistent, recurrent, or metastatic 
cervical cancer who were also receiving chemotherapy with or without bevacizumab (Colombo 
2021).  
No established standard of care has been identified for patients with cervical cancer who 
progress on or after 1L therapy. Single-agent modalities have reported response rates between 
0 and 15% and an OS between 6.6 and 7.4 months (Miller 2008); (Bookman 2000); (Garcia 
2007); (Muggia 2004); (Monk 2009); (Santin 2011). Furthermore, toxicity is substantial with 
many of these agents, thus limiting their overall benefit-risk profile. 

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The lack of effective treatments, high risk of relapse, and substantial toxicity associated with 
currently administered therapies warrant the development of novel, safe, and effective therapies 
that result in markedly improved clinical benefit for these patients. 
2.1.2. 
Study Population  
Tisotumab vedotin has shown activity in previously treated participants with r/mCC (see 
Section 2.2.3). The current study will limit inclusion to participants with 1 or 2 prior lines of 
systemic therapy. The eligibility criteria specify that participants must have received 
bevacizumab and/or anti-PD-(L)1 agent in combination with paclitaxel+carboplatin, 
paclitaxel+cisplatin, or paclitaxel+topotecan, if eligible to receive bevacizumab and/or 
anti-PD-(L)1 agent according to local standards, as these combination regimens are identified 
standard of care therapies for the treatment of 1L r/mCC. To ensure that the population enrolled 
in this study reflects the approximate global utilization of bevacizumab, the percent of 
participants who have not received a bevacizumab combination as a 1L therapy may be capped 
at 50%. 
2.1.3. 
Control Arm  
As previously mentioned, a standard of care has not been established for the r/mCC patient 
population, and multiple systemic therapies including chemotherapy and targeted agents have 
been evaluated but with very limited activity. Topoisomerase I inhibitors (ie, irinotecan, 
topotecan), multitargeted anti-folate (pemetrexed), antimitotic agents (ie, vinorelbine), and 
antimetabolite agents (ie, gemcitabine) are among the most commonly used agents and are listed 
as global treatment options in both the European Society for Medical Oncology (ESMO) and 
National Comprehensive Cancer Network (NCCN) guidelines (Marth 2017); (Koh 2019). 
The International Conference on Harmonisation (ICH) E10 guideline on “Choice of Control 
Group and Related Issues in Clinical Trials” indicates that in such cases where there are no 
standard treatment regimens and since no single regimen can be defined, an active comparator of 
investigator’s choice is often preferable (ICH 2000). Because this study will be conducted 
globally, it is necessary to minimize variables that could lead to increased heterogeneity and bias. 
Thus, the treatment options for the control arm from which the investigator can choose have been 
predefined (refer to Section 4). The specified starting doses and treatment schedules for each of 
the options are based on scientific literature and recommendations provided in treatment 
guidelines (Bookman 2000); (Muggia 2004); (Lilly USA 2018); (Takeuchi 1991); (Verschraegen 
1997); (Lorusso 2010). The chemotherapy options offer different mechanisms of action and 
safety profiles that can be used (per investigator’s choice and local regulations) depending on the 
participant’s prior therapies and overall medical condition. 
2.2. 
Background  
2.2.1. 
Overview of the Disease  
Cervical cancer has an estimated incidence of more than 500,000 new cases per year globally, 
accounting for approximately 8% of cancer-related deaths in female patients (Bray 2018). 
According to National Cancer Institute estimates, more than 291,000 women are living with 
invasive cervical cancer in the US, and approximately 13,800 new cases will be diagnosed in 

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2020. More than 4,290 women in the US will die from the disease this year (National Cancer 
Institute (NCI) 2020). 
For the vast majority of patients diagnosed with r/mCC, platinum-based chemotherapy regimens 
were the 1L standard of care for many years. More recently, a systemic combination therapy of 
bevacizumab with either cisplatin+paclitaxel or paclitaxel+topotecan was established as the 
standard of care for 1L treatment of patients with persistent, r/mCC based on the Gynecologic 
Oncology Group (GOG) 240 trial. Median OS was increased by 3.7 months in the bevacizumab 
arm (17.0 months vs. 13.3 months with chemotherapy alone, hazard ratio [HR] 0.71). The 
objective response rate (ORR) was substantially higher in the bevacizumab arm (48% vs. 36%), 
and PFS was substantially prolonged (8.2 months vs. 5.9 months) (Tewari 2014). The addition of 
bevacizumab to chemotherapy was associated with an increased incidence of hypertension of 
grade 2 or higher (25% vs. 2%), thromboembolic events of grade 3 or higher (8% vs. 1%), and 
gastrointestinal fistulas of grade 3 or higher (3% vs. 0%). This regimen is the standard of care for 
the 1L treatment of r/mCC for patients who are eligible to receive bevacizumab. While definitive 
data are lacking, physician surveys suggest that approximately 55% and 47% of patients with 
cervical cancer in the US and Europe, respectively, are treated with the GOG 240 regimen in the 
1L setting (cancermpact.com). 
In the KEYNOTE-826 study, pembrolizumab, an anti-PD-(L)1 agent, met the dual primary 
endpoints of PFS and OS in patients with persistent, recurrent, or metastatic cervical cancer who 
were also receiving chemotherapy with or without bevacizumab (Colombo 2021). 
Treatment options after the 1L are limited, and no standard of care therapies have been 
identified. Single-agent cytostatic therapies are the mainstay of treatment; however, median 
survival is <9 months, and robust phase 2 or 3 data are lacking. Multiple cytostatic agents for the 
treatment of patients with cervical cancer who progress on or after 1L treatment are available, 
including vinorelbine, topotecan, irinotecan, pemetrexed, gemcitabine, or nanoparticle albumin-
bound paclitaxel. However, modest response rates and limited evidence of durability are 
observed with these therapies (Marth 2017); (Koh 2019). 
Recently, pembrolizumab, a programmed cell death protein 1 (PD-1) inhibitor, received 
accelerated approval in the US for the treatment of patients with programmed cell death ligand 
1 (PD-L1) positive (combined proportioned score ≥1) or microsatellite instability high/deficient 
mismatch repair cervical cancer who have demonstrated disease progression on or after 
chemotherapy. An ORR of 14% and a disease control rate of 31% was observed among 77 
previously treated patients with advanced cervical cancer who had PD-L1 expression of ≥1% 
(Merck & Co Inc 2018). 
2.2.2. 
Introduction to the Investigational Medicinal Product  
TF is a transmembrane glycoprotein that in normal physiology is the main initiator of the 
extrinsic coagulation pathway. In malignant cells, strict regulation of TF is lost, and it is 
aberrantly expressed in tumor cells and associated stromal cells of the tumor microenvironment. 
Published reports and sponsor studies demonstrate TF expression in a variety of malignancies, 
often correlating with increased metastatic properties, angiogenesis, tumor initiation, tumor 
growth, and poor disease prognosis (Kakkar 1995; Rickles 1995; Sawada 1999; Kaushal 2008; 
Milsom 2008; Cocco 2011a). Procoagulant activity and intracellular signaling induced by TF 
may enhance metastatic potential, angiogenesis, and cell survival in tumor cells (Ruf 1996). 

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Immunohistochemistry (IHC) analysis of TF expression in cervical cancer tissue 
(adenocarcinoma and squamous cell carcinoma) demonstrated high prevalence of TF expression 
in the tested patient population, with 96% of evaluable patient biopsies showing TF expression at 
variable intensities (Data on file from GCT1015-04 pivotal phase 2 trial). Comparison between 
cervical cancer biopsies and a small set of normal cervix biopsies showed enhanced TF staining 
intensity and a higher frequency of TF-positive cells in malignant tissues, demonstrating 
differential expression (Cocco 2011b; Srinivasan 2011). 
The investigational medicinal product, tisotumab vedotin, is an antibody-drug conjugate (ADC) 
composed of a human monoclonal immunoglobulin G1 (subtype κ) targeting TF conjugated via a 
protease cleavable valine citrulline linker to the drug monomethyl auristatin E (MMAE), a 
dolastatin 10 analog (Doronina 2003); (Hamblett 2004); (Sun 2005). Dolastatins and auristatins 
belong to a class of chemotherapies that act as microtubule disrupting agents (Chen 2017). 
Tisotumab vedotin binds to TF-expressing tumor cells, followed by internalization of the 
ADC-TF complex, and the local release of MMAE via proteolytic cleavage (Breij 2014). MMAE 
disrupts the microtubule network of actively dividing cells, leading to cell cycle arrest and 
apoptotic cell death. Released MMAE can diffuse out of the cell into the tumor 
microenvironment and enter neighboring cells by passive diffusion (Okeley 2010). If the 
neighboring cell is undergoing active cell division, then MMAE can once again induce cell cycle 
arrest and apoptotic death–a process called bystander cytotoxicity–independent of the 
neighboring cell’s TF expression level (Breij 2014). The direct cytotoxicity of Tisotumab 
vedotin may be augmented by the immune-mediated tumor cell killing effects of antibody-
dependent cell-mediated cytotoxicity, antibody-dependent cellular phagocytosis, and 
immunogenic cell death clinic (Alley 2019). Finally, in vivo anti-tumor activity of tisotumab 
vedotin was demonstrated in multiple tumor types in mouse efficacy models implanted with cell 
line-derived and patient-derived tumor xenografts. 
Tisotumab vedotin had no toxicologically meaningful effects on coagulation and bleeding events 
in cynomolgus monkeys with regards to untoward secondary effects of binding TF. While in 
vitro evidence suggests biological plausibility for tisotumab vedotin to alter TF-dependent 
initiation of coagulation, downstream physiological processes related to coagulation and 
bleeding have not manifested nonclinically. Further details of nonclinical studies can be found in 
the Investigator’s Brochure. 
2.2.3. 
Summary of Clinical Trials  
Tisotumab vedotin is in clinical development for the treatment of various solid tumors 
expressing TF, including cervical cancer. As of July 2020, there are 8 completed or ongoing 
clinical trials with tisotumab vedotin for the treatment of cervical cancer and other solid tumors: 
GEN701, GEN702, GCT1015-03, GCT1015-04, GCT1015-05, GCT1015-06, SGNTV-001, and 
SGNTV-002. 
GCT1015-04 is a pivotal phase 2, single-arm, global trial of tisotumab vedotin in 101 
participants with previously treated recurrent or metastatic cervical cancer. Eligible participants 
had 2L or 3L r/mCC and had experienced disease progression on or after receiving a 
chemotherapy doublet (paclitaxel + cisplatin/carboplatin OR paclitaxel + topotecan) in 
combination with bevacizumab, if eligible to receive such treatment/s according to local 
standards. Prior chemoradiation with curative intent was not considered a line of therapy for the 

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purposes of the trial. Participants were treated with IV tisotumab vedotin 2.0 mg/kg every 3 
weeks (Q3W) until disease progression or unacceptable toxicity. Imaging was obtained every 
6 weeks for the first 30 weeks and every 12 weeks thereafter until each participant experienced 
disease progression, began a new anti-cancer therapy, withdrew from the trial, or died. 
Responses were confirmed at least 4 weeks (28 days) after the first assessment of response. 
The primary endpoint was confirmed ORR based upon Response Evaluation Criteria in Solid 
Tumors (RECIST) v1.1, assessed by independent review committee (IRC). Secondary endpoints 
included duration of response (DOR), time to response (TTR) and PFS assessed by IRC and 
confirmed ORR, DOR, TTR, and PFS assessed by investigator, OS, and safety and tolerability. 
All radiographic secondary efficacy endpoints were based upon RECIST v1.1. 
At the 06 Feb 2020 data cutoff for primary analysis, treatment with tisotumab vedotin in 
GCT1015-04 resulted in a clinically meaningful confirmed ORR per IRC of 24% [95% CI: 
15.9%-33.3%] in participants with previously treated r/mCC, with 7 participants achieving a 
complete response (CR). Responses were generally consistent with the overall trial population 
across the subgroups analyzed and observed regardless of TF expression levels. 
Responses were durable, with a median DOR of 8.3 months (95% CI 4.2 months – not reported 
[NR]). This DOR compares favorably with the limited DOR data available for single agent 
chemotherapies, which present historical median DORs ranging from 3 to 6 months. 
Additionally, an estimated 62% of responses to tisotumab vedotin remained ongoing at 6 
months. 
Tisotumab vedotin had a manageable and tolerable safety profile in this population of 2L and 3L 
participants with recurrent or metastatic cervical cancer. The most common treatment-emergent 
adverse events (TEAEs) included nausea (41 participants, 41%), alopecia (39 participants, 39%), 
epistaxis (39 participants, 39%), fatigue (35 participants, 35%), anemia (34 participants, 34%), 
and conjunctivitis (31 participants, 31%). 
Certain TEAEs are identified as adverse events of special interest (AESIs) as follows: bleeding 
adverse event (AE) (TF plays a key physiologic role in clotting initiation); ocular AE 
(hypothesized as TF-mediated, due to TF expression on conjunctiva); peripheral neuropathy 
(known neurotoxic potential of MMAE). These AESIs including ocular AEs, peripheral 
neuropathy, and bleeding events were generally mild to moderate in nature (grades 1 and 2) and 
were effectively managed with dose modifications and supportive care. Please refer to the 
Investigator’s Brochure for additional information. 
In summary, the efficacy and safety data from GCT1015-04 demonstrate the potential for 
tisotumab vedotin to substantially improve clinical outcomes with a manageable safety profile in 
participants with r/mCC with disease progression on or after chemotherapy. 
2.3. 
Benefit/Risk Assessment  
Data from GCT1015-04 demonstrate clinically meaningful efficacy of tisotumab vedotin in 
participants with r/mCC along with a manageable safety profile (Section 2.2.3). Given the 
limited efficacy achieved with currently available therapies for patients with advanced or 
metastatic cervical cancer (Section 2.1.1), safety and efficacy data from the GCT1015-04 trial 
suggest a positive benefit-risk profile and warrant further investigation of tisotumab vedotin in 
participants with cervical cancer who have progressed on 1L therapy. This population represents 

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a substantial high unmet need and further investigation of treatments such as tisotumab vedotin 
that have novel mechanisms of action are needed to potentially extend and improve the quality of 
the lives of these patients. Known risks to participants from tisotumab vedotin include ocular 
adverse events, peripheral neuropathy, and epistaxis. Potential risks include bleeding events, 
cytopenia, skin toxicity, gastrointestinal disorders, and infusion-related reactions. Additional 
potential risks as described in the Investigator’s Brochure pertain to pregnancy and lactation and 
immunogenicity. 
The following risk mitigation measures are being employed to ensure the safety of participants in 
this trial: 
• Formation of an independent data monitoring committee (IDMC) to monitor safety of 
tisotumab vedotin in participants. 
• Identification of AESIs and implementation of preventative mitigation measures for 
each, when appropriate (see Section 6.6.2), that are informed by prior clinical trials as 
well as thought leader input. 
Preliminary safety and activity data from the tisotumab vedotin clinical trials suggest a positive 
benefit-risk profile. More detailed information about the known and expected benefits and risks 
and reasonably expected AEs of tisotumab vedotin may be found in the Investigator’s Brochure.

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3. 
OBJECTIVES AND ENDPOINTS  
Objectives and related endpoints are described in Table 4. 
Table 4: 
Objectives and Endpoints 
OBJECTIVES 
ENDPOINTS 
Primary 
● Demonstrate improvement in clinical efficacy of 
tisotumab vedotin compared to chemotherapy in 
participants with 2L-3L cervical cancer 
● OS 
Secondary 
● Assess improvement in clinical efficacy of tisotumab 
vedotin compared to chemotherapy in participants 
with 2L-3L cervical cancer 
● PFS based on RECIST v1.1 as assessed by the 
investigator 
● Demonstrate improvement in antitumor activity of 
tisotumab vedotin compared to chemotherapy in 
participants with 2L-3L cervical cancer 
● Confirmed ORR based on RECIST v1.1 as assessed 
by the investigator 
● Characterize the antitumor response of tisotumab 
vedotin and chemotherapy in participants with 2L-3L 
cervical cancer 
● Time-to-response (TTR) as assessed by the 
investigator 
● DOR as assessed by the investigator  
● Evaluate the safety and tolerability of tisotumab 
vedotin 
● Incidence of AEs 
● Assess health-related quality of life (HRQOL) 
● EQ-5D-5L index 
● EQ-5D visual analog scale (VAS) 
● EORTC-QLQ-C30 
● EORTC-QLQ-CX24 
Exploratory 
● Investigate the relationship between TF tumor 
expression and response to tisotumab vedotin  
● Tumor TF expression (via immunohistochemistry 
[IHC] or RNA) in relation to efficacy endpoints 
● Assess biomarkers and their association with disease, 
mechanisms of resistance, and/or response to therapy 
● Baseline characteristics and changes from Baseline 
of biomarkers from peripheral blood and/or 
formalin-fixed paraffin-embedded (FFPE) tumor 
tissue in relation to efficacy endpoints 
● Evaluate the pharmacokinetics (PK) and 
immunogenicity of tisotumab vedotin 
● PK concentrations and anti-drug antibodies (ADAs) 
associated with tisotumab vedotin 
 

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4. 
STUDY DESIGN  
4.1. 
Overall Design  
This is an open-label, randomized (1:1), global, phase 3 study of tisotumab vedotin versus 
investigator’s choice of chemotherapy in participants with r/mCC who have received 1 or 2 prior 
lines of systemic therapy for their recurrent or metastatic disease. Eligible participants will be 
randomized to either tisotumab vedotin 2.0 mg/kg Q3W or investigator’s choice of 
chemotherapy (See Section 4.3). No crossover between treatment arms is permitted. The term 
“study treatment” is used hereafter to refer to either tisotumab vedotin or any of the 
chemotherapy options. 
Randomization will be stratified by Eastern Cooperative Oncology Group (ECOG) performance 
status (0 vs. 1), prior bevacizumab administration (yes vs. no), region (US, EU, Other), and prior 
anti-PD-(L)1 administration (yes vs. no). Imaging will be obtained every 6 weeks (42 days ±7 
days) for the first 30 weeks and then every 12 weeks (84 days ±7 days) thereafter, calculated 
from Cycle 1 Day 1 (C1D1) of treatment administration. Imaging must continue until evidence 
of radiographic disease progression per RECIST v1.1 as assessed by investigator (see 
Section 7.1.2) or until the start of new anti-cancer treatment, withdrawal of consent, death, or the 
end of the study, whichever occurs first. Survival status will be assessed every 60 days (±7 days) 
beginning from the day of the last dose of study treatment, or more frequently around the time of 
a database lock. Approximately 482 participants will be randomized in the study. The design 
schema of the study is shown in Section 1.2. 
4.2. 
Scientific Rationale for Study Design  
Participants will be randomized 1:1 to one of the 2 arms to minimize bias in the assessment of 
treatment effects. The investigator’s choice of chemotherapy must be assigned and recorded for 
each participant prior to randomization. Randomization will be stratified by ECOG performance 
status, prior bevacizumab, region, and prior anti-PD-(L)1 therapy, as these are considered 
medically important prognostic factors and to ensure balance across these treatment groups, 
which could potentially influence the primary outcome, OS. The proportion of participants who 
have not received prior bevacizumab in combination with chemotherapy as 1L treatment may be 
capped at 50%, given that 50% represents the approximate utilization of bevacizumab in 
combination with chemotherapy as 1L standard of care in patients with cervical cancer. 
Blinding of the study is not operationally feasible due to the substantial differences in toxicity 
profile, cycle lengths, treatment administration, and premedications of the control arm treatment. 
Therefore, the study design will be open-label with the investigator, participants, and sponsor 
unblinded to treatment assignment. The evaluation of clinical effectiveness will be based on OS, 
which was selected as the primary endpoint as the most relevant and preferred endpoint in 
oncology in accordance with regulatory guidance. 
As no approved standard of care is available in the study population, the comparator treatment 
for tisotumab vedotin is investigator’s choice from a set of defined, available, commonly used 
chemotherapies in this setting. An interim analysis (IA) will be conducted to enable a potentially 
earlier assessment of whether tisotumab vedotin clearly prolongs OS compared to chemotherapy. 
An IDMC, consisting of members who are external and independent of the sponsor study team, 
will be formed to monitor the safety of participants in this study on a periodic basis, review 

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safety and efficacy data from this study as per planned analyses, and make recommendations to 
the sponsor. Refer to the IDMC charter for details. 
4.3. 
Justification for Dose  
Participants will be treated with either tisotumab vedotin 2.0 mg/kg IV Q3W or investigator’s 
choice of chemotherapy. The 2.0 mg/kg dose of tisotumab vedotin was identified as the 
recommended phase 2 dose in Part 1 of Trial GEN701 and was further evaluated in multiple 
dose-expansion cohorts during which additional safety and efficacy data were collected. The 
investigator’s choice chemotherapy options are:  
• Topotecan 1 or 1.25 mg/m2 IV on Days 1 to 5, every 21 days 
• Vinorelbine 30 mg/m2 IV on Days 1 and 8, every 21 days 
• Gemcitabine 1000 mg/m2 IV on Days 1 and 8, every 21 days 
• Irinotecan 100 or 125 mg/m2 IV weekly for 28 days, every 42 days 
• Pemetrexed 500 mg/m2 on Day 1, every 21 days 
Although there is no defined standard of care treatment for patients with r/mCC who have 
progressed during or after 1L treatment, there are small, single-agent, single-institution trials that 
support the use of certain chemotherapies in this setting (Table 5). These chemotherapy options 
and the respective doses and schedules are considered acceptable treatment options for a control 
arm and are all, or mostly, included in the NCCN (Koh 2019), ESMO (Marth 2017), and 
Japanese guidelines (Ebina 2019). 
Table 5: 
Clinical Outcomes in the Second Line and Beyond 
Author 
Agent 
N 
ORR (%) 
PFS 
OS  
(Muggia 2004) 
Vinorelbine 
44 
13.7 
NR 
NR 
(Bookman 2000) 
Topotecan 
45 
12.5 
2.1 months 
6.6 months 
(Schilder 2005) 
Gemcitabine 
22 
4.5 
2.1 months 
6.5 months 
(Verschraegen 1997) 
Irinotecan 
42 
21 
NR 
6.4 months 
(Lorusso 2010) 
Pemetrexed 
43 
13.9 
10 weeks 
35 weeks 
4.4. 
End of Study Definition  
4.4.1. 
End of Study Definition  
The study is considered completed when the last survival follow-up visit is completed or 5 years 
after randomization of the last participant participating in the study, whichever occurs first. 
4.4.2. 
Study Termination  
The sponsor reserves the right to close a site or terminate the study at any time for any reason at 
the sole discretion of the sponsor. Safety will be monitored throughout the study. If new or 
emerging safety information that affects the benefit/risk assessment of the trial negatively 
emerges, the trial will be discontinued. Sites will be closed upon study completion.  

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The investigator may initiate site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for early closure of a site by the sponsor or investigator include but are not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the 
Independent Ethics Committee (IEC)/Institutional Review Board (IRB) or local 
health authorities, the sponsor's procedures, or ICH Good Clinical Practice (GCP) 
guidelines 
• Inadequate recruitment of participants by the investigator 
• Discontinuation of further tisotumab vedotin development 
• If the development of the tisotumab vedotin is discontinued, or study closure is 
necessary, the sponsor will ensure provisioning of post-study treatment for ongoing 
study participants 
The sponsor will consult with the investigator, as appropriate, regarding the potential for 
continuation of study treatment for any participant continuing to benefit from tisotumab vedotin 
at the time the study is completed. 

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5. 
STUDY POPULATION  
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1. 
Inclusion Criteria  
Each potential participant must fulfill all of the following criteria to be enrolled in the study. 
Note that further inclusion criteria may apply to each of the chemotherapy options and that the 
investigator should assess eligibility based upon local labeling or institutional guidelines prior to 
identifying the chemotherapy they would administer, if the participant is randomized to the 
control arm. 
1. Age ≥18 years, or considered an adult by local regulations, at time of consent. 
2. Must sign an informed consent form (ICF) indicating that they understand the purpose of 
and procedures required for the study and are willing to participate in the study prior to 
any other study-related assessments or procedures. 
3. Has recurrent or metastatic cervical cancer with squamous cell, adenocarcinoma, or 
adenosquamous histology, and: 
a. Has experienced disease progression during or after treatment with a standard of care 
systemic chemotherapy doublet, or platinum-based therapy (if eligible), defined as 
either:  
− paclitaxel+cisplatin+bevacizumab+ anti-PD-(L)1 agent, or 
− paclitaxel+carboplatin+bevacizumab+ anti-PD-(L)1 agent, or 
− paclitaxel+topotecan/nogitecan+bevacizumab+ anti-PD-(L)1 agent 
NOTE: only in cases where bevacizumab and/or anti-PD-(L)1 agent is not a standard of 
care therapy or the participant was ineligible for such treatment according to local 
standards, prior treatment with bevacizumab and/or anti-PD-(L)1 agent is not required. 
b. Has received 1 or 2 prior systemic therapy regimens for recurrent and/or metastatic 
cervical cancer. Chemotherapy administered in the adjuvant or neoadjuvant setting, or 
in combination with radiation therapy, should not be counted as a systemic therapy 
regimen. Single agent therapy with an anti-PD(L)1 agent for r/mCC should be 
counted. 
c. Is not a candidate for curative therapy, including but not limited to radiotherapy or 
exenterative surgery. 
4. Measurable disease according to RECIST v1.1 as assessed by the investigator, defined as: 
a. A minimum of one non-nodal lesion ≥10 mm in the longest diameter from a non-
irradiated area. If target lesion(s) are located within previously irradiated area only, 
the participant can be enrolled only if there has been demonstrated progression in the 
“in field” lesion and upon approval of the sponsor’s medical monitor. 
OR 
b. Lymph node lesion ≥15 mm in the shortest diameter from a non-irradiated area. 

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5. Must demonstrate acceptable screening laboratory values: 
 
Laboratory Test 
Value 
 
Renal Function 
A1 
Calculated eGFR (MDRD formula) 
≥50 mL/min/1.73m2 
 
Liver Function 
B1 
Alanine aminotransferase (ALT)  
≤3× upper limit of normal (ULN) (if liver 
tumor/metastases are present, then ≤5×ULN is 
allowed) 
B2 
Aspartate aminotransferase (AST) 
≤3×ULN (if liver tumor/metastases are present, then 
≤5×ULN is allowed) 
B3 
Bilirubin 
≤1.5×ULN (except in participants diagnosed with 
Gilbert’s syndrome, direct bilirubin ≤2×ULN) 
 
Hematological Statusa (assessed at least 1 week after transfusion with blood products and/or growth 
factor support) 
C1 
Hemoglobin 
≥5.6 mmol/L (9.0 g/dL) 
C2 
Absolute neutrophil count (ANC)  
≥1500/µL (1.5x109/L) 
C3 
Platelet count 
≥100×109/L 
 
Coagulation Statusb 
For participants NOT on anti-coagulation therapy 
D1 
Activated partial thromboplastin time (aPTT) 
≤1.5×ULN 
D2 
International normalized ratio (INR) 
≤1.2 
 
Coagulation Statusb 
For participants on anti-coagulation therapyc 
E1 
aPTT 
≤1.5×ULN 
E2 
INR 
≤2.5d 
a. 
Acceptable hematologic status must be met without erythropoietin administration and packed red blood cell 
transfusion or G-CSF within 1 week of C1D1. 
b. Acceptable coagulation status must be met within 1 week of C1D1 
c. 
Concurrent chronic use of prophylactic acetylsalicylic acid (eg, aspirin) or chronic anti-platelet therapy is 
prohibited for participants on any type of anti-coagulation therapy. 
d. Participants that require laboratory assessments for dose titration (warfarin or other vitamin K dependent 
anticoagulant agents) must be on a steady dose (no active titration) for ≥4 weeks prior to C1D1. 
 
6. Has ECOG performance status of 0 or 1 prior to randomization. 
7. Has life expectancy of at least 3 months. 
8. Has a negative serum pregnancy test for participants of reproductive potential. 
Participants that are postmenopausal, permanently sterilized or previously subjected to 
bilateral oophorectomy, bilateral salpingectomy and/or hysterectomy can be considered 
as not having reproductive potential (refer to Section 10.4). 
9. Participants of reproductive potential must agree to use adequate contraception during 
and for 6 months after the last study treatment administration. Adequate contraception is 

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defined as highly effective methods of contraception (refer to Section 10.4). Two highly 
effective methods of contraception must be used in countries where this is required. 
10. Must agree not to breastfeed or donate ova, starting at the time of informed consent and 
continuing through 6 months after receiving the last dose of study drug administration. 
11. Where required by local health authorities, has negative serology for hepatitis B surface 
antigen (HBsAg)/HBV DNA, or hepatitis C antibody (HCVAb) or RNA. Active hepatitis 
C is defined by a known positive HCVAb result and known quantitative HCV RNA 
results greater than the lower limits of detection of the assay. 
12. Must be willing and able to adhere to the prohibitions and restrictions specified in this 
protocol. 
5.2. 
Exclusion Criteria  
A potential participant who meets any of the following criteria will be excluded from 
participating in the study. Note that further exclusion criteria may apply to each of the 
chemotherapy options and that the investigator should assess eligibility based upon local labeling 
or institutional guidelines prior to identifying the chemotherapy they would administer, if the 
participant is randomized to the control arm. 
1. Has primary neuroendocrine, lymphoid, sarcomatoid, or other histologies not mentioned 
in inclusion criterion 3 (refer to Section 5.1). 
2. Has clinically significant bleeding issues or risks:  
a. Known past or current coagulation defects leading to an increased risk of bleeding 
b. Diffuse alveolar hemorrhage from vasculitis 
c. Known bleeding diathesis 
d. Ongoing major bleeding (ie, participant requires a transfusion of >2 platelet 
concentrates within 14 days of the first dose of study treatment) 
e. Trauma with increased risk of life-threatening bleeding 
f. History of severe head trauma or intracranial surgery within 8 weeks of study entry. 
3. Has cardiovascular issues or risks: 
a. Clinically significant cardiac disease, including unstable angina or acute myocardial 
infarction, 6 months prior to screening 
b. Any medical history of congestive heart failure (grade III or IV as classified by the 
New York Heart Association) 
c. Any medical history of decreased cardiac ejection fraction of <45% 
d. A marked baseline prolongation of QT/QTc interval (eg, repeated demonstration of a 
QTc interval >450 msec) 
e. A complete left bundle branch block (defined as a QRS interval ≥120 msec in left 
bundle branch block form) or an incomplete left bundle branch block 
4. Central nervous system (CNS): any history of intracerebral arteriovenous malformation, 
cerebral aneurysm, or stroke (transient ischemic attack >1 month prior to screening is 
allowed). 

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5. Ophthalmological: Active ocular surface disease or a history of cicatricial conjunctivitis 
or inflammatory conditions that predispose to cicatrizing conjunctivitis (eg, Wagner 
syndrome, atopic keratoconjunctivitis, autoimmune disease affecting the eyes), ocular 
Stevens-Johnson syndrome or toxic epidermal necrolysis, mucus pemphigoid, and 
participants with penetrating ocular transplants are ineligible. Cataracts alone is not an 
exclusion criterion. 
6. Other cancer: known past or current malignancy other than inclusion diagnosis. 
Exceptions are malignancies with a negligible risk of metastasis or death (e.g., 5-year OS 
≥90%) such as non-invasive basal cell or squamous cell skin carcinoma, non-invasive, 
superficial bladder cancer, and ductal carcinoma in situ. 
7. Brain metastases are allowed if the following criteria are met: definitive therapy (eg, 
surgery or stereotactic brain radiotherapy) has been completed >8 weeks before the first 
dose of study treatment; no evidence of clinical or radiologic progression of the brain 
metastases; participant has completed perioperative corticosteroid therapy or steroid 
taper. NOTE: Chronic steroid therapy is acceptable provided that the dose is stable for 1 
month prior to screening. 
8. Surgery/procedures: major surgery within 4 weeks or minor surgery within 7 days prior 
to the first study treatment administration. Participants must have recovered adequately 
from the toxicity or complications from the intervention prior to starting study treatment. 
Participants who have planned major surgery during the treatment period must be 
excluded from the study. 
9. Peripheral neuropathy ≥grade 2. 
10. Prior anti-cancer therapy: 
a. Any prior treatment with MMAE-derived drugs. 
b. Radiotherapy within 21 days prior to the first administration of study treatment. 
Participants must have recovered from all clinically significant radiation-related 
toxicities. At least 42 days must have elapsed from the last administration of 
chemo-radiotherapy. 
c. Small molecules, chemotherapy, immunotherapy, or monoclonal antibodies within 
28 days prior to the first administration of study treatment. 
d. Currently participating in or has participated in a study of an investigational agent or 
device and received active treatment within 28 days prior to the first dose of study 
treatment. 
11. Other: 
a. Ongoing significant, uncontrolled medical condition. 
b. Clinically significant active viral, bacterial, or fungal infection requiring IV or oral 
treatment with antimicrobial therapy ending <7 days prior to first study treatment 
administration. 
c. Clinically relevant bilateral hydronephrosis which cannot be alleviated by ureteral 
stents or percutaneous drainage. 
d. Participants with clinical symptoms or signs of gastrointestinal obstruction and who 
require parenteral hydration or nutrition at the time of the first dose of study 
treatment.  

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12. Has known seropositivity of human immunodeficiency virus (HIV); known medical 
history of hepatitis B or C infection. Note: No testing for HIV, hepatitis B, or hepatitis C 
is required, unless mandated by local health authorities. Exceptions include latent or 
controlled HIV infection. 
13. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (dose 
exceeding 10 mg daily of prednisone or equivalent) or any other form of 
immunosuppressive therapy within 7 days prior to the first dose of tisotumab vedotin. 
14. Is pregnant or intends to conceive children within 6 months of ending study treatment. 
15. Is breast feeding and cannot discontinue breast feeding for the duration of the study and 
≥6 months after the last study treatment administration. 
16. Any condition for which, in the opinion of the investigator, participation would not be in 
the best interest of the participant (eg, compromise well-being) or that could prevent, 
limit, or confound the protocol-specified assessments. 
17. Known allergies, hypersensitivity, or intolerance to study treatment or its excipients 
(refer to the Investigator's Brochure for further information on tisotumab vedotin). 
18. Has known psychiatric or substance abuse disorders that would interfere with cooperating 
with the requirements of the study. 
5.3. 
Lifestyle Considerations  
Participants who receive tisotumab vedotin are advised not to wear contact lenses during the 
treatment phase of the study. 
To minimize possible contributing factors to the development of dry eye during the treatment 
phase of the study, participants are encouraged to cleanse the face and thoroughly remove 
makeup nightly, especially around the eyelids and eyelashes (ie, to remove eye shadows, 
mascara, and eye liner). 
Also to minimize dry eye, it is recommended that participants limit screen time on 
digital/electronic devices during the treatment phase of the study. The sponsor recommends the 
“20/20/20 Rule”: for every 20 minutes spent focusing on a digital screen, spend at least 20 
seconds looking at an object that is at least 20 feet away. In addition, it is recommended to adjust 
indoor lighting to avoid glare on electronic devices. 
5.4. 
Screen Failures  
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently entered in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility criteria, 
and any serious adverse event (SAE). 
Individuals who do not meet the criteria for participation in this study (screen failures) may be 
rescreened. Rescreened participants should be assigned a different participant number from the 
initial screening. Upon rescreening, all eligibility criteria must be re-assessed by the investigator. 

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Results from assessments performed during the previous screening period are acceptable for 
rescreening purposes if performed within the specified time frame and the inclusion/exclusion 
criteria are met: 
• Previously obtained chest X-ray (CXR), computed tomography (CT) or magnetic 
resonance imaging (MRI) scans are valid for rescreening purposes if the scanning 
acquisition date is ≤28 days prior to C1D1. 
• Already completed HRQOL questionnaires are valid if they have been completed ≤7 
days prior to C1D1. 
• Blood samples taken during the previous screening process are valid for rescreening 
purposes as long as they fulfill the initial timelines as indicated in Table 1 and 
Table 3. The same tumor biopsy sample is valid for rescreening purposes. 

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6. 
STUDY INTERVENTION  
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according to the 
study protocol. 
6.1. 
Study Intervention(s) Administered  
The term “study treatment” is used hereafter to refer to either: 
• tisotumab vedotin 2.0 mg/kg every 21 days (Q3W), or 
• any of the chemotherapy options. The investigator's choice chemotherapy options are: 
− Topotecan 1 or 1.25 mg/m2 IV on Days 1 to 5, every 21 days 
− Vinorelbine 30 mg/m2 IV on Days 1 and 8, every 21 days 
− Gemcitabine 1000 mg/m2 IV on Days 1 and 8, every 21 days 
− Irinotecan 100 or 125 mg/m2 IV weekly for 28 days, every 42 days 
− Pemetrexed 500 mg/m2 on Day 1, every 21 days 
Study treatment will be administered until one of the criteria for treatment discontinuation is met 
(see Section 7.1). 
6.1.1. 
Tisotumab Vedotin Arm  
Tisotumab Vedotin 
Tisotumab vedotin is an ADC composed of an IgG1 human monoclonal antibody chemically 
conjugated via a protease cleavable valine citrulline linker to the drug MMAE. 
Physical Description of Tisotumab Vedotin 
Tisotumab vedotin is presented as a lyophilized powder for reconstitution in water for injection 
and is intended for IV dosing by infusion after dilution in physiological saline solution, 5% 
Dextrose Injection, USP; or Lactated Ringer’s Injection, USP. It is manufactured and provided 
under the responsibility of the sponsor. A list of excipients can be found in the Investigator’s 
Brochure. 
Tisotumab Vedotin Dosage and Administration 
Tisotumab vedotin 2.0 mg/kg will be administered as an IV infusion on Day 1 of each 3-week 
treatment cycle (21 days) after all procedures and assessments have been completed. Tisotumab 
vedotin should be administered over a minimum of 30 minutes and it is recommended not to 
exceed 60 minutes. Sites should make every effort to target infusion timing to be as close to 
30 minutes as possible. 
Each participant’s dose will be calculated based on the participant’s weight (as described in 
Section 8.3.1) and may be rounded to the nearest kilogram, ie, 2.0 mg/kg × body weight in kg. 
For participants who weigh >100 kg, the calculation of the tisotumab vedotin dose should be 
normalized to 100 kg (ie, 2.0 mg/kg × 100 kg = 200 mg). 

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The Pharmacy Manual contains specific instructions for the preparation of the tisotumab vedotin 
infusion and administration of infusion solution. 
As a routine precaution, participants dosed with tisotumab vedotin must be monitored during 
infusion and treated in an area with resuscitation equipment and emergency agents. All 
participants should be observed for 2 hours after ending their first infusion of tisotumab vedotin 
and 15 minutes for all subsequent cycles. 
Preventive eye therapy must be administered in relation to each administration of tisotumab 
vedotin as described in Section 6.5.1.1. 
6.1.2. 
Chemotherapy Control Arm  
The investigator’s choice chemotherapy options are: 
• Topotecan 1 or 1.25 mg/m2 IV on Days 1 to 5, every 21 days 
• Vinorelbine 30 mg/m2 IV on Days 1 and 8, every 21 days 
• Gemcitabine 1000 mg/m2 IV on Days 1 and 8, every 21 days 
• Irinotecan 100 or 125 mg/m2 IV weekly for 28 days, every 42 days 
• Pemetrexed 500 mg/m2 on Day 1, every 21 days 
For the investigator’s choice of chemotherapy options, doses are weight-based. For C1D1, the 
investigator should use screening weight to calculate the dose, but C1D1 weight is also allowed 
to be used, per investigator discretion. Weight is measured at the start of each cycle. If there is a 
≥10% change in weight, the investigator’s choice chemotherapy dose should be recalculated. 
6.2. 
Preparation/Handling/Storage/Accountability  
General Procedures 
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study intervention received and any discrepancies are 
reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study intervention 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access limited to 
the investigator and authorized site staff. 
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
4. Further guidance and information for the final disposition of unused study interventions 
are provided in the Pharmacy Binder. 
6.2.1. 
Tisotumab Vedotin  
Packaging and Labeling of Tisotumab Vedotin 

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Tisotumab vedotin will be supplied to the study site pharmacy as single vial cartons. Tisotumab 
vedotin will be supplied in vials containing 40 mg of tisotumab vedotin as lyophilized powder. 
The powder must be reconstituted with 4 mL water for injection leading to a 10 mg/mL solution. 
Tisotumab vedotin will not be dispensed in child-resistant packaging. 
Labeling will be in accordance with the applicable local regulatory requirements. For further 
details, please refer to the Pharmacy Binder. 
Preparation, Handling, and Storage of Tisotumab Vedotin 
Tisotumab vedotin (lyophilized vials) must be stored in a refrigerator at 2°C to 8°C. The dose of 
tisotumab vedotin for administration must be prepared by the study site pharmacy using aseptic 
technique. The reconstituted tisotumab vedotin must be diluted into 0.9% NaCl 100 mL infusion 
bag according to the dose calculated for the participant. Refer to the Pharmacy Manual for 
instructions on storage, preparation, and infusion of tisotumab vedotin. 
6.2.2. 
Chemotherapy Control Arm  
Topotecan, vinorelbine, gemcitabine, irinotecan, and pemetrexed will be provided or reimbursed 
by the sponsor. Refer to the Pharmacy Binder and local label for instructions on storage, 
preparation, and administration. 
6.2.3. 
Drug Accountability  
The investigator or designee should maintain an accurate record of the shipment and dispensing 
of study treatment in accordance with the transactions in the Randomization and Trial Supply 
Management (RTFM) system. Drug accountability will be verified by the field monitor during 
site visits and at the completion of the study. 
Drug accountability procedures are provided in the Pharmacy Binder. 
6.2.3.1. 
Technical Complaint Handling  
A technical complaint is defined as any suspicion of a product defect related to manufacturing, 
labeling, or packaging, ie, any dissatisfaction relative to the identity, quality, durability, or 
reliability of a product, including its labeling or package integrity. A technical complaint may 
have an impact on the safety and efficacy of the product. Timely, accurate, and complete 
reporting and analysis of technical complaint information from studies are crucial for the 
protection of participants, investigators, and the sponsor, and are mandated by regulatory 
agencies worldwide. The sponsor has established procedures in conformity with regulatory 
requirements worldwide to ensure appropriate reporting of technical complaint information; all 
studies conducted by the sponsor or its affiliates will be conducted in accordance with those 
procedures. 
Procedures 
All initial technical complaints must be reported to the sponsor by the site personnel within 
24 hours after being made aware of the event. 
If the defect is combined with an AE, the site personnel must report the AE to the sponsor 
according to the AE and SAE reporting process and timelines (Section 8.4) in addition to 

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reporting the technical complaint. A sample of the suspected product should be maintained for 
further investigation if requested by the sponsor. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding  
This is an open-label study. Although this is an open label study, to maintain trial integrity, 
analyses or summaries by randomized treatment or actual treatment assignment will be limited 
and documented while the study is ongoing and before the database lock for primary analyses.  
Randomization will be used to avoid bias in the assignment of participants to treatment groups, 
to increase the likelihood that known and unknown participant attributes (eg, demographic and 
baseline characteristics) are evenly balanced across treatment groups, and to ensure the validity 
of statistical comparisons across treatment groups. The study has 2 treatment arms, and 
randomization will occur centrally using an RTSM system. Participants will be assigned 
randomly in a 1:1 ratio to either tisotumab vedotin or chemotherapy. The investigator’s choice of 
chemotherapy must be assigned and recorded for each participant prior to randomization. 
Additionally, the proportion of participants who have not received prior bevacizumab in 
combination with chemotherapy as 1L treatment may be capped at 50%. Randomization will be 
stratified according to the following factors: 
• ECOG performance status: 0 vs. 1 
• Prior bevacizumab therapy: yes vs. no 
• Prior anti-PD-(L)1 therapy: yes vs. no 
• Region: US, EU, Other 
6.4. 
Study Intervention Compliance  
Study drug will be administered by site personnel to assure compliance with study requirements. 
6.5. 
Concomitant Therapy  
6.5.1. 
Premedications and Supportive Care  
6.5.1.1. 
Tisotumab Vedotin Arm  
Premedication for Tisotumab Vedotin 
MANDATORY Prophylaxis of Ocular AEs: 
In order to reduce the incidence and severity of ocular AEs, all participants randomized to 
tisotumab vedotin must adhere to the following ocular premedication guidelines: 
• Administration of local ocular vasoconstrictor before infusion (brimonidine tartrate 
0.2% eye drops or similar, 3 drops in each eye immediately prior to start of infusion; 
otherwise to be used in accordance with the product prescribing information). If the 
participant does not tolerate ocular vasoconstrictors due to adverse reactions, 
continued treatment with these may be stopped at the discretion of the investigator 
and following discussion with the sponsor’s medical monitor. 

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• Use of eye cooling pads during infusion. Cooling pads must cover both eyes (such as 
an eye mask or cold pack/s) and should be applied 5 minutes prior to start of infusion 
in accordance with the instructions provided with the eye cooling pads. The cooling 
pads must remain on the participant’s eyes during the entire 30 to 60 minute infusion 
and for as long as 30 minutes afterwards. 
• Application of steroid eye drops (dexamethasone 0.1% eye drops or equivalent) 
before and after each infusion for a total of 4 days. The first drops are to be given 
24 hours prior to start of infusion. Continue treatment for 72 hours thereafter. Steroid 
eye drops should be administered as 1 drop in each eye, 3 times daily, or used in 
accordance with the product prescribing information. 
• Use of lubricating eye drops during the whole treatment phase of the trial (ie, from 
first dose of study drug until 30 days after the last dose of study drug). Frequent use 
of lubricating eye drops as per standard of care for participants receiving 
chemotherapy is recommended. Lubricating eyedrops should be self-administered 
daily according to the package insert or prescribed instructions from the 
ophthalmologist. 
• It is recommended not to wear contact lenses while being treated with tisotumab 
vedotin from the first dose until 30 days after the last dose of study drug. 
Note that prophylactic premedication does not qualify as an intervention when assessing 
Common Terminology Criteria for Adverse Events (CTCAE) grading of treatment-emergent 
ocular AEs. 
Supportive Care for Tisotumab Vedotin 
Refer to Section 6.6 for additional information regarding dose modification and safety 
management. 
Prophylaxis of alopecia: 
DigniCap Scalp Cooling System or similar systems should be considered, if allowed per local 
guidance, to mitigate chemotherapy-induced hair loss. 
Prophylaxis of nausea: 
Prophylactic treatment with anti-emetics and anti-pyretics (eg, paracetamol) is strongly 
suggested for participants experiencing nausea ≥ grade 1 after cycle 1. 
Recurrent infusion-related reactions (IRRs): 
In case of an IRR ≥ grade 2, the participant should receive premedication prior to the next 
infusion of tisotumab vedotin (antihistamine, acetaminophen, and/or corticosteroids are 
recommended). 
Recurrent neutropenia: 
In case of neutropenic sepsis or neutropenia grade 3 or 4, granulocyte colony-stimulating 
factor (G-CSF) should be given prophylactically for all subsequent tisotumab vedotin 
administrations. 
6.5.1.2. 
Chemotherapy Control Arm  
Premedication for Chemotherapy Arm 

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For the chemotherapy arm, administration of premedication should be performed per local 
labeling or institutional guidelines. 
Supportive Care for Chemotherapy Arm 
Supportive care for alopecia, IRRs, and bone marrow toxicity (eg, anemia, neutropenia, 
thrombocytopenia) should be administered per local standards. Anti-emetics should be 
administered per local standards for ≥ grade 1 nausea or vomiting. Any additional supportive 
care measures for toxicities identified with the chemotherapies should be administered per local 
guidelines. 
6.5.2. 
Permitted Concomitant Medications and Therapies  
All treatments that the investigator considers necessary for a participant’s welfare and according 
to local labeling or institutional guidelines may be administered at the discretion of the 
investigator in keeping with the community standards of medical care except for those 
medications identified as “prohibited” (Section 6.5.3). The participant should be told to notify 
the study site about any new medications taken after the time of informed consent. 
The timing for collection of concomitant medications is specified in Table 1 and Table 3. 
Concomitant medications administered beyond 30 days after the last dose of study treatment 
should be recorded for SAEs and AESIs. 
6.5.2.1. 
Permitted Concomitant Medications and Therapies for Tisotumab 
Vedotin Arm  
Anti-coagulation therapy is permitted. Participants being treated with anti-coagulation therapy 
that requires laboratory assessments for dose titration (warfarin or other vitamin K dependent 
anticoagulant agents) should have their doses adjusted to target an INR ≤2.5 and must be on a 
steady dose (no active titration) for at least 4 weeks prior to C1D1. Coagulation parameters, 
including aPTT and INR, must be measured prior to each infusion of tisotumab vedotin as per 
the assessment schedule. 
6.5.2.2. 
Permitted Concomitant Therapy for Tisotumab Vedotin Arm Requiring 
Caution or Action  
Drugs and substances known to be strong CYP3A or P-gp inhibitors according to the US FDA’s 
list of drug interactions should be avoided if possible (FDA 2016). Please see 
https://www.fda.gov/drugs/developmentapprovalprocess/developmentresources/druginteractionsl
abeling/ucm093664.htm for these lists. If administered, the participant should be closely 
observed for potential adverse reactions. 
6.5.2.3. 
Permitted Concomitant Therapy for the Chemotherapy Arm  
For the chemotherapy arm, permitted concomitant medications and therapies should be provided 
as per local labeling or institutional guidelines. 
6.5.3. 
Prohibited Concomitant Therapy  
Participants should be instructed not to take any medications, including over-the-counter 
products, without first consulting with the investigator. Medications specifically prohibited in the 

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exclusion criteria are not allowed during the study. If there is a clinical indication for any 
medication specifically prohibited during the study, discontinuation from study treatment may be 
required. The investigator should discuss any questions regarding this with the sponsor. The final 
decision on any supportive therapy rests with the investigator or the participant's primary 
physician. However, the decision to continue the participant on study treatment requires the 
mutual agreement of the investigator, the sponsor, and the participant. 
The following is prohibited for participants receiving tisotumab vedotin: 
• Chronic prophylactic treatment with acetylsalicylic acid (eg, aspirin) or chronic anti-
platelet therapy in combination with any other anti-coagulation therapy. 
The following are prohibited for participants receiving tisotumab vedotin or chemotherapy: 
• Investigational agents 
• Any other anti-cancer therapy, (eg, immunotherapy, monoclonal antibodies, hormonal 
therapy) 
• MMAE-derived drugs 
• Radiotherapy (note: radiation therapy of a symptomatic solitary non-target lesion or 
to the brain may be allowed at the investigator’s discretion) 
The following are prohibited for participants receiving chemotherapy: 
• Any drugs that are contraindicated for use with the assigned chemotherapy 
• Any other anti-cancer therapy that has not been identified as investigator’s choice 
6.6. 
Dose Modification  
6.6.1. 
Dose Modifications for Tisotumab Vedotin  
6.6.1.1. 
Dose Reduction for Tisotumab Vedotin  
For participants who do not tolerate the protocol-specified dosing schedule, dose reductions are 
permitted in order to allow the participant to continue treatment with tisotumab vedotin. Dose 
reductions must be preapproved by the sponsor’s medical officer unless permitted according to 
the dose modification guidelines provided below (Section 6.6.2, Table 6). 
In case any dose reduction of tisotumab vedotin is needed, the dose must be reduced according to 
the guidelines provided below (Table 6). Dose reductions below 0.9 mg/kg are not permitted. 
Thus, if an AE requiring dose reduction recurs after the second dose reduction of tisotumab 
vedotin, the participant must permanently discontinue tisotumab vedotin treatment. 
Table 6: 
Tisotumab Vedotin Dose Modification Scheme 
Previous dose of tisotumab vedotin 
Reduced dose of tisotumab vedotin 
2.0 mg/kg 
1.3 mg/kg 
1.3 mg/kg 
0.9 mg/kga 
a. 
Dose reductions below 0.9 mg/kg are not permitted. 

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6.6.1.2. 
Dose Delay for Tisotumab Vedotin  
Any dose delay resulting from AE(s) that delay(s) treatment with tisotumab vedotin for more 
than 21 days (delay is counted from date of planned dosing) must be approved by the sponsor’s 
medical officer unless allowed according to the mitigation plans specified in the protocol (refer 
to Section 6.6.2). 
For any dose delay due to AEs, dosing with tisotumab vedotin can be resumed immediately after 
the AE has improved as indicated in the guidance specified in Section 6.6.2. Tisotumab vedotin 
must be permanently discontinued for any dose delay >6 weeks, (ie, 42 days calculated from the 
intended day of the next scheduled dose), unless approved by the sponsor. 
6.6.2. 
Dose Modification Guidelines and Preventive Measures for Specific AEs 
Observed with Tisotumab Vedotin  
6.6.2.1. 
Ocular AEs  
The ocular mitigation plan may be modified, by the ophthalmologist or optometrist based on findings on the 
ocular examination obtained on either baseline or on-treatment examinations. Sponsor consultation is required 
prior to any modification. 
● All participants must adhere to all ocular preventive measures (refer to Section 6.6.2.1.1 and Section 6.5.1.1). 
● In case of ocular AEs, participants must be referred to an ophthalmologist or optometrist for prompt 
ophthalmological evaluation (within approximately 72 hours). The participant should thereafter be followed 
closely by the ophthalmologist or optometrist until resolution. Topical treatment should be initiated by the 
ophthalmologist or optometrist according to the treatment guidelines below.  
● If ≥3 ocular AEs occur in a participant, sponsor consultation is required to determine if dose modifications or 
treatment discontinuation is warranted. 
 
Grading: All ocular AEs should be graded according to both: 
CTCAE grading system; assessed by the ophthalmologist based on NCI-CTCAE criteria (CTCAE version 5.0). 
Note that prophylactic premedication does not qualify as an intervention when assessing CTCAE grading of 
treatment-emergent ocular AEs. 
Dose Modification for Ocular AEs (based on CTCAE grading) 
Conjunctivitis  
Conjunctivitis 
grade 1 
Hold dosing until event is managed effectively  
Continue same dose for next dosing 
Conjunctivitis 
grade 2  
first occurrence 
Hold dosing until event has improved to ≤ grade 1 
Continue same dose for next dosing 
Conjunctivitis 
grade 2 
second occurrence 
Hold dosing.  
● If the event resolves (to baseline) within 6 weeks (calculated from the onset date of the 
second occurrence of the grade 2 event), the participant can resume tisotumab vedotin 
dosing at a reduced dose according to the dose reduction scheme (Table 6) 
● If the event does not resolve (to baseline) within 6 weeks, the participant must 
permanently discontinue tisotumab vedotin treatment 
Conjunctivitis 
grade 2 
third occurrence 
Permanently discontinue tisotumab vedotin treatment 

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Conjunctivitis 
≥grade 3 
Permanently discontinue tisotumab vedotin treatment 
Keratitis  
Keratitis grade 1 
 
Hold dosing until event is managed effectively 
Continue same dose for next dosing 
Keratitis grade 2 
first occurrence 
Hold dosing until event has improved to ≤ grade 1 
Reduce next dose according to dose reduction scheme 
Keratitis grade 2 
second occurrence 
Hold dosing until event has improved to ≤ grade 1 
Further reduce next dose according to dose reduction scheme 
Keratitis grade 2 
third occurrence 
Permanently discontinue tisotumab vedotin treatment 
Keratitis ≥grade 3 
Permanently discontinue tisotumab vedotin treatment 
Conjunctival ulceration and ophthalmological findings of fluorescent patches  
Any grade 
first occurrence 
Hold dosing until event is managed effectively 
Reduce next dose according to dose reduction scheme 
Any grade 
≥second 
occurrence 
If symptoms do not stabilize/improve after dose reduction, the participant must 
permanently discontinue tisotumab vedotin treatment 
Symblepharon  
Any grade 
Permanently discontinue tisotumab vedotin treatment 
Conjunctival or corneal scarring 
Any grade 
Permanently discontinue tisotumab vedotin treatment 
All other ocular AEsa 
All other ocular 
AEs grade 1 
Hold dosing until event is managed effectively  
Continue same dose for next dosing  
All other ocular 
AEs grade 2 
first occurrence 
Hold dosing until event has improved to ≤ grade 1 
Continue same dose for next dosing 
All other ocular 
AEs grade 2 
second occurrence 
Hold dosing.  
● If the event resolves (to baseline) within 6 weeks (calculated from the onset date of the 
second occurrence of the grade 2 event), the participant can resume tisotumab vedotin 
dosing at a reduced dose (according to the dose reduction scheme). 
● If the event does not resolve (to baseline) within 6 weeks, the participant must 
permanently discontinue tisotumab vedotin treatment 
All other ocular 
AEs grade 2 
third occurrence 
Permanently discontinue tisotumab vedotin treatment 
All other ocular 
AEs ≥grade 3 
Permanently discontinue tisotumab vedotin treatment 
a. 
Unless more strict mitigation is indicated by sponsor 

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6.6.2.1.1. Ocular Preventive Measures  
In order to prevent ocular AEs, all participants randomized to tisotumab vedotin must adhere to 
the ocular premedication guidelines specified in Section 6.5.1.1. 

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6.6.2.1.2. Guidelines for Treatment Prescribed by the Ophthalmologist or 
Optometrist  
Ocular symptom (CTCAE grading) 
Treatment guideline 
(The length of treatment is to be decided by the local ophthalmologist) 
Conjunctivitis grade 1 
Frequent dosing of preservative-free topical steroid drops is 
recommended. 
Conjunctivitis grade 2 
Frequent dosing (every second hour) of preservative-free topical 
steroid drops in conjunction with preservative-free antibiotic 
prophylaxis such as chloramphenicol is recommended. 
Conjunctivitis grade 3 
Frequent dosing (every second hour) of preservative-free topical 
steroid drops in conjunction with preservative-free antibiotic 
prophylaxis such as chloramphenicol is recommended. 
Keratitis grade 1 
Frequent dosing of preservative-free topical steroid drops is 
recommended. 
Keratitis grade 2 
Frequent dosing (every second hour) of preservative-free topical 
steroid drops in conjunction with preservative-free antibiotic 
prophylaxis such as chloramphenicol is recommended. 
Conjunctival ulceration: any grade 
Frequent dosing (every second hour) of preservative-free topical 
steroid drops in conjunction with preservative-free antibiotic 
prophylaxis such as chloramphenicol is recommended. 
 
 
 

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6.6.2.2. 
Other AEs for Tisotumab Vedotin  
Dose Modification Guidelines for Other AEs (based upon CTCAE grading) 
Bleeding events 
● Control vital signs and ensure stabilization of the participant according to local standards. 
● Prompt evaluation to identify the underlying etiology of the bleeding event. Management should be dictated by 
the underlying diagnosis. 
● Control laboratory coagulation and hematologic parameters including prothrombin (PT), aPTT, fibrinogen, 
platelets, INR, and hemoglobin as soon as possible. 
All participants: 
Any grade pulmonary or 
CNS hemorrhage 
Permanently discontinue tisotumab vedotin treatment. 
Hemorrhage (other)a 
≥grade 4 
Permanently discontinue tisotumab vedotin treatment. 
Participants not on anti-coagulation therapy: 
Hemorrhage (other)a  
grade 3 
first occurrence 
Hold dosing until: 
a) Bleeding has resolved. 
b) Blood hemoglobin level is stable.  
c) There is no bleeding diathesis that could increase the risk of continuing therapy.  
d) There is no anatomical or pathologic condition that can increase the risk of 
hemorrhage recurrence.  
 
When the above criteria are fulfilled, the participant can resume treatment with 
tisotumab vedotin at the same dose as prior to the event. 
Hemorrhage (other)a  
grade 3 
≥second occurrence 
Contact the sponsor’s medical officer in order to discuss whether the participant can 
continue or must permanently discontinue tisotumab vedotin treatment. 
Participants on anti-coagulation therapy: 
INR >3.0 with ongoing 
hemorrhage (other)a 
≤grade 2 
Participants on therapeutic anti-coagulation whose INR is >3.0 prior to infusion of 
tisotumab vedotin must hold dosing until INR is ˂3.0. Participants may resume 
tisotumab vedotin administration immediately after the INR is ˂3.0. Strongly consider 
holding anti-coagulation until the above parameters are met. 
Hemorrhage (other)a 
≥grade 3 
Hold anti-coagulation therapy. 
Contact the sponsor’s medical officer in order to discuss whether the participant can 
continue or must permanently discontinue tisotumab vedotin treatment. 
INR requirements for participants on anti-coagulants who are not experiencing a bleeding event 
INR >3.0 
Participants on warfarin or other vitamin K dependent anticoagulant agents whose INR 
is >3.0 prior to infusion of tisotumab vedotin must hold dosing until INR is <3.0. 
Participants may resume tisotumab vedotin administration immediately after the INR 
is <3.0. Strongly consider holding anti-coagulation until the above parameters are met. 
a. 
Any other hemorrhage with the exception of pulmonary or CNS hemorrhage. 

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Dose Modification Guidelines for Other AEs (based upon CTCAE grading) (cont.) 
Infusion-Related Reactions (IRRs) 
● As a routine precaution, participants enrolled in this study must be monitored during infusion and treated in an 
area with resuscitation equipment and emergency agents.  
● All participants should be observed for 2 hours after ending their first infusion of tisotumab vedotin and 15 
minutes for all subsequent cycles. 
● In case any clinically significant IRR is observed during or after the first infusion of tisotumab vedotin or at 
subsequent treatment cycles, the participant should be observed for 2 hours after ending the administration of 
tisotumab vedotin for all subsequent infusions. 
● At all times during infusion, immediate emergency treatment of an anaphylactic reaction according to institutional 
standards must be assured. In order to treat possible anaphylactic reactions, for instance, dexamethasone 10 mg 
and epinephrine in a 1:1000 dilution or equivalents must always be available along with equipment for assisted 
ventilation. 
Grade 1 
Continue infusion at the investigator’s discretion at half the infusion rate under close 
medical supervision. 
Grade 2  
Infusion must be interrupted and appropriate medical management instituted. 
The infusion may be re-started at the investigator’s discretion at half the infusion rate 
under close medical supervision, if symptoms have resolved to ≤grade 1 within an 
hour. 
The participant should receive premedication (antihistamine, acetaminophen and 
corticosteroids are recommended) before next infusion. 
Grade 3 
first occurrence 
Infusion must be interrupted and appropriate medical management instituted. 
The infusion may be re-started at the investigator’s discretion at half the infusion rate 
under close medical supervision if symptoms have resolved to ≤grade 1 within an 
hour. 
The participant should receive premedication (antihistamine, acetaminophen, and 
corticosteroids are recommended) before next infusion. 
Grade 3 
second occurrence despite 
premedication 
Permanently discontinue tisotumab vedotin treatment. 
≥Grade 4 
Infusion must be interrupted immediately and appropriate medical therapy must be 
administered. Permanently discontinue tisotumab vedotin treatment. 
Liver parameters elevated 
Grade 3 
Contact the sponsor’s medical officer before next dosing of the participant, in order to 
decide whether next dose of tisotumab vedotin should be reduced, next dosing 
delayed, or tisotumab vedotin should be permanently discontinued. 
≥Grade 4 
Permanently discontinue tisotumab vedotin treatment. 
Mucositis 
Grade 3 
Hold dose until event has improved to ≤ grade 2. 
Start treatment according to local practice. 
≥ Grade 4 
Permanently discontinue tisotumab vedotin treatment. 
Neutropenia 

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Grade 3 or  
1st occurrence of grade 4 
Hold dosing until event has improved to ≤ grade 2 (including G-CSF administration) 
G-CSF may be given prophylactically for subsequent tisotumab vedotin 
administrations.  
Grade 4  
2nd occurrence 
Contact sponsor’s Medical Officer in order to discuss dose reduction or 
discontinuation of tisotumab vedotin. 
Peripheral neuropathy (including PTs as: neuropathy peripheral, peripheral sensory neuropathy, peripheral motor 
neuropathy, polyneuropathy) 
Grade 2 and 3 
Initial or worsening of 
pre-existing condition 
Hold dosing until event has improved to ≤ grade 1 
Reduce next dose according to dose reduction scheme (Table 6). 
≥ Grade 4 
Permanently discontinue tisotumab vedotin treatment. 
6.6.3. 
Dose Modifications for the Chemotherapy Control Arm  
Dose modifications for the chemotherapy arm should always be performed as per local labeling 
or institutional guidelines. Appendix 7 (Section 10.7) provides toxicity management 
recommendations for selected AEs that are characteristic for the investigator’s choice 
chemotherapy agents. 
6.7. 
Intervention after the End of the Study  
No interventions are planned after the end of the study. 

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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL  
7.1. 
Discontinuation of Study Treatment  
A participant’s study treatment may be discontinued for any of the following reasons: 
• Unacceptable AE requiring treatment discontinuation (see Section 8.4)* 
• Death 
• Pregnancy 
• Participant withdrawal of consent from the study  
• Participant request to discontinue study treatment*  
• Clinical progression* 
• Radiographic evidence of disease progression 
• Investigator decision 
• Other 
*Despite treatment discontinuation, imaging should continue to be performed until evidence of 
radiographic disease progression or until the start of new anti-cancer treatment, withdrawal of 
consent, death, or the end of the study, whichever occurs first. 
When a participant discontinues study treatment, they are to remain on study and are to be 
followed until death, initiation of subsequent therapy, or any other reason listed in Section 7.2. 
7.1.1. 
Summary of Safety Stopping Rules  
Tisotumab vedotin treatment must be permanently discontinued in case the participant fulfills 
any of the below criteria. Treatment discontinuation for the chemotherapy administered in the 
control arm should be done per local labeling or institutional guidelines. 
Tisotumab vedotin discontinuation criteria for ocular AEs: 
• Second occurrence of CTCAE grade 2 conjunctivitis that does not resolve to baseline 
within 6 weeks 
• Third occurrence of CTCAE grade 2 conjunctivitis 
• First occurrence of CTCAE ≥ grade 3 conjunctivitis  
• Third occurrence of CTCAE grade 2 keratitis 
• First occurrence of CTCAE ≥ grade 3 keratitis 
• Ophthalmological evaluation reveals conjunctival/corneal scarring 
• Any grade of symblepharon 
• Second occurrence of any grade of fluorescent patches or conjunctival ulceration 

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• Second occurrence of all other ocular CTCAE grade 2 AEs that does not resolve 
within 6 weeks 
• Third occurrence of all other ocular CTCAE grade 2 AEs 
• First occurrence of all other ocular CTCAE ≥ grade 3AEs 
• Any dose delay >6 weeks calculated from the intended day of the next scheduled 
dose, unless approved by the sponsor 
Tisotumab vedotin discontinuation criteria for other AEs: 
• Any grade pulmonary or CNS hemorrhage 
• First occurrence of a ≥ grade 4 hemorrhage (other) 
• Second occurrence of a grade 3 IRR (despite premedication) 
• First occurrence of a ≥ grade 4 IRR 
• First occurrence of mucositis ≥ grade 4 
• First occurrence of liver parameter elevated ≥ grade 4  
• First occurrence of peripheral neuropathy ≥ grade 4 
• Any dose delay > 6 weeks calculated from the intended day of the next scheduled 
dose, unless approved by the sponsor 
7.1.2. 
End of Treatment Visit  
When study treatment is permanently discontinued, investigators are to perform an end of 
treatment visit. The end of treatment visit should be performed 30 days (±5 days) after the 
participant has received the last dose of study treatment (Table 1 and Table 3). 
7.1.2.1. 
Post-Study Treatment Anti-Cancer Therapy Status  
If a participant initiates a new anti-cancer therapy within 30 days after the last dose of study 
treatment, the 30-day end of treatment visit should occur before the first dose of the new therapy, 
if possible. Once new anti-cancer therapy has been initiated, the participant will enter survival 
follow-up. 
7.1.2.2. 
Survival Follow-up  
Information about survival status and initiation of any new anti-cancer therapy should be 
collected every 60 days (±7 days) (or more frequently around the time of a database lock), 
beginning from the day of last study treatment dose until death or withdrawal from study. If for 
any reason a participant enrolled into the study comes off treatment prior to receiving study drug, 
survival follow-up can be collected from the date of the EOT visit or day of EOT if no visit 
occurred. Survival follow-up can be performed by telephone contact (the participant or a family 
member may give the requested information) or during a routine visit, if such a visit is scheduled 
for other reasons not related to this study. This should be documented in the medical records. 
Information related to subsequent progression after initiation of new anti-cancer therapy or death 
from any cause, whichever comes first, is to be collected. 

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7.2. 
Participant Discontinuation/Withdrawal from the Study  
Participants are to be withdrawn from the study for the following reasons: 
• Death  
• Lost to follow-up (see Section 7.3) 
• Study termination by sponsor 
• Participant withdrawal of consent 
• Other 
If the participant withdraws consent for disclosure of future information, the sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. A participant may 
choose to discontinue from any future study assessments (eg, dosing, imaging, blood sampling, 
etc.) but agree to remain in the study and to be followed for survival follow-up, without 
withdrawal of consent. If a participant withdraws consent from the study, they may request 
destruction of any samples taken and not tested, and the investigator must document this in the 
site study records. Study drug assigned to the withdrawn participant may not be assigned to 
another participant. Participants who withdraw will not be replaced. The investigator and sponsor 
will make every effort to ensure participant data are followed for completion of all study safety 
assessments including end of treatment follow-up and survival follow-up (refer to Table 1 and 
Table 3) at the time of study discontinuation. 
7.2.1. 
Follow-up for Safety Evaluations  
All participants will have safety evaluations at 30 days after the last dose of study treatment at 
the end of treatment visit (refer to Table 1 and Table 3). Some AEs may be followed beyond this 
period (refer to Section 8.4.3). 
7.3. 
Lost to Follow up  
A participant will be considered lost to follow-up if they repeatedly fail to return for scheduled 
visits and are unable to be contacted by the study site. 
For participants whose status is unclear because they fail to appear for study visits without 
stating an intention to withdraw consent, the investigator should show "due diligence" by 
contacting the participant, family, or family physician as agreed in the ICF and by documenting 
in the source documents steps taken to contact the participant, eg, dates of telephone calls, 
registered letters, etc. A participant should not be considered lost to follow-up until due diligence 
has been completed (minimum of 3 documented attempts). Participants lost to follow-up should 
be recorded as such on the appropriate disposition electronic case report form (eCRF). 
Discontinuation of specific sites or of the study as a whole are handled as part of Appendix 1 
(Section 10.1). 

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8. 
STUDY ASSESSMENTS AND PROCEDURES  
• Study procedures and their timing are summarized in the schedule of activities (SoA) 
(Section 1.3). Protocol waivers or exemptions are not allowed. 
• Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
• All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log 
to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable. 
• Procedures conducted as part of the participant’s routine clinical management (eg, 
blood count) and obtained before signing of the ICF may be utilized for screening or 
baseline purposes provided the procedures met the protocol-specified criteria and 
were performed within the time frame defined in the SoA. 
8.1. 
Demography and Baseline Assessments  
8.1.1. 
Demographics  
Demographic details must be assessed and recorded in the eCRF at screening. 
8.1.2. 
Diagnosis and Disease Status  
A participant’s history relating to the underlying disease, including primary diagnosis, date of 
diagnosis, and disease status at study entry, will be recorded at screening. 
8.1.3. 
Medical History  
Medical history is defined as all relevant past and all current medical conditions/diseases 
(besides cervical cancer) occurring prior to first dose (refer to Section 8.4.2 for details on the 
timing of AE reporting). Medical history includes all active conditions, and any condition 
diagnosed within the prior 10 years that are considered to be clinically significant by the 
investigator. Any abnormalities identified during screening prior to C1D1, including baseline 
ocular assessment, should be entered into the participant’s medical history. Details regarding the 
cancer for which the participant has enrolled in the study will be recorded separately and not 
listed as medical history. 
8.1.4. 
Concomitant Medication  
Investigators may prescribe concomitant medications or treatments deemed necessary to provide 
adequate supportive care except for those medications identified as “prohibited” (Section 6.5.3). 
The participant should be told to notify the study site about any new medications they are taking. 
All medications and significant non-drug therapies (including herbal/natural medications and 
blood transfusions) administered during the study must be recorded in the eCRF from the time of 
informed consent and up to 30 days after the last dose of study treatment. Thereafter only new 
anti-cancer therapy will be collected as noted in Table 1 and Table 3. 

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8.1.5. 
Prior Cancer Therapy and Surgery  
Administration of prior anti-cancer therapies for treatment of cervical cancer (including surgery, 
radiotherapy, chemo-radiotherapy, systemic therapy regimens, etc.) from the time of the initial 
cervical cancer diagnosis until enrollment in this study must be reported in the appropriate 
section of the eCRF. 
8.2. 
Efficacy Assessments  
8.2.1. 
Tumor Imaging  
Tumor images will be reviewed by the local investigator. Images will also be collected for a 
potential blinded independent central review. 
The imaging process is described in a separate imaging guidance document. Tumor imaging 
should be performed by CT (preferred), unless otherwise indicated in the imaging guidance 
document. MRI should be used only when CT is contraindicated, for imaging of the CNS, or for 
certain anatomical regions (see imaging guidance document). The same imaging technique with 
respect to the modality and use of contrast should be used in a participant throughout the study to 
optimize the visualization of existing and new tumor burden. Determination of measurable 
disease based on RECIST v1.1 will be conducted by the local site investigator during screening 
for assessment of participant eligibility and during the study for assessment of response. 
8.2.1.1. 
Baseline Imaging Assessments  
Baseline imaging assessments will be performed at screening within 28 days of start of treatment 
(Day -28 to Day -1 prior to C1D1). 
Any imaging assessments considered of adequate diagnostic quality already completed during 
the regular evaluation of the participant within 28 days prior to start of treatment, including 
before signing the main study ICF, can be considered as the baseline images for this study. Any 
imaging assessments obtained after randomization cannot be considered baseline images. 
The following assessments are required at screening: 
Contrast-enhanced chest, abdomen, and pelvis CT or MRI scan 
All participants will have a contrast-enhanced CT or contrast-enhanced MRI scan of the 
abdomen and pelvis and a non-contrast CT of the chest. 
If a participant is known to have a contraindication to CT IV contrast media or develops a 
contraindication during the study, a non-contrast CT of the chest plus a contrast-enhanced 
MRI (if possible) of the abdomen and pelvis should be performed. 
It is strongly recommended that MRI is used for evaluation of lesion(s) present within an 
irradiated field. Tumors within a previously irradiated field will be designated as “non-
target” lesions unless progression is documented or a biopsy is obtained to confirm 
persistence at least 90 days following completion of radiation therapy. Biopsy confirmation 
MAY be considered for either target or non-target lesions if the lesion(s) measures <30 mm 
or if the treating physician determines it is clinically indicated. If a biopsy is performed on a 
previously irradiated lesion, an MRI (or CT if MRI is contraindicated) should be obtained 

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following the biopsy procedure and before the start of treatment for use as the baseline 
screening exam. 
Chest X-rays (CXRs) and ultrasound imaging should not be used to measure tumor lesions. 
Chest X-ray 
A CXR is acceptable at screening in lieu of a chest CT only if the local standard of care does 
not support a chest CT and the CXR does not show evidence of metastases. Otherwise, a 
chest CT is required.  
If a baseline CXR shows no evidence of metastatic disease, subsequent imaging should also 
be performed with CXR; however, a chest CT scan must be obtained upon identification of 
lesions after baseline. 
If a baseline CXR shows evidence of metastatic disease, a CT of the chest must be obtained 
and followed for progression and response per the imaging schedule defined above. 
Brain CT or MRI scan (if clinically indicated) 
In order for participants with previously treated brain metastases to be eligible to participate 
in the study, documented stability by brain imaging over at least 4 weeks is required, and 
there must be confirmation of no new or enlarging brain metastases within 28 days of the 
first dose of study treatment. If brain metastases are suspected at screening, brain MRI or CT 
scans should be completed. A contrast-enhanced brain MRI is preferred; however, if MRI 
contrast is contraindicated, then an MRI without contrast or CT with/without contrast is 
acceptable. For any participant with known brain metastases at screening, and who achieves 
a CR during study treatment, a follow-up brain scan is required for confirmatory assessment 
of CR. 
Whole-body bone scan (if clinically indicated) 
For any participant with an elevated screening serum alkaline phosphatase level (1.5×ULN 
range), bone imaging (eg, bone scan or positron-emission tomography [PET] scan) should be 
conducted to identify possible bone metastases if clinically suspected. If bone metastases are 
identified that have not been imaged on the CT/MRI performed for baseline tumor imaging 
(Section 8.2.1.1), then additional baseline and all subsequent tumor imaging studies must 
include such lesions in the imaging field. A whole-body bone scan should be performed per 
institutional standard of care (eg, Tc-99 bone scan, whole body bone MRI, FDG-PET or 
NaF-PET). Combined PET/CT may be used only if the CT is of similar diagnostic quality as 
a CT performed without PET, including the utilization of IV contrast media. At the discretion 
of the investigators, FDG-PET scans may be performed to document disease progression as 
per RECIST v1.1 (Eisenhauer 2009). 
CT or MRI scan of other metastatic sites (if clinically indicated) 
If clinically indicated, CT or MRI of other areas (eg, neck) of disease, as appropriate, should 
be performed. 

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8.2.1.2. 
Post baseline imaging assessments  
Table 7: 
Imaging Assessment Collection Plan 
Procedure 
Screening/Baseline 
During Treatment/Follow-up 
Chest, abdomen, and pelvis CT or 
MRI (with IV contrast 
enhancement)  
Mandated 
Mandated, every 6 weeks 
(±7 days) 
 
Brain CT or MRI 
If clinically indicated 
If lesions were documented at 
baseline, follow same schedule as 
CT/MRI of chest, abdomen, and 
pelvis 
Whole-body bone scan 
If clinically indicated 
If clinically indicated 
Localized bone CT or MRI  
For any lesions identified on the 
whole-body bone scan that are not 
visible on the chest, abdomen and 
pelvis CT or MRI 
If lesions were documented at 
baseline, follow same schedule as 
CT/MRI of chest, abdomen, and 
pelvis 
CT or MRI of other metastatic 
sites (eg, neck) 
If clinically indicated 
If lesions were documented at 
baseline, follow same schedule as 
CT/MRI of chest, abdomen, and 
pelvis 
Note: CXR is acceptable at screening in lieu of a chest CT if the local standard of care does not support a chest CT. 
 
Imaging assessments as described in Table 7 should be performed at the time points specified 
using the same imaging modality used at baseline, irrespective of study treatment interruption or 
actual dosing. Imaging assessments for response evaluation will be performed every 6 weeks 
(42±7 days) after screening/baseline during the first 30 weeks, and every 12 weeks (84±7 days) 
thereafter, or more frequently if clinically indicated. Imaging assessments should be scheduled 
using the first dosing date as the reference date (not the date of the previous tumor assessment) 
and should be respected regardless of whether treatment with study treatment is temporarily 
withheld or unscheduled assessments performed. 
Additional imaging assessments may be performed at any time during the study at the 
investigator’s discretion to support the efficacy evaluations for a participant, as necessary. 
Clinical suspicion of disease progression at any time requires a physical examination and 
imaging assessments to be performed promptly rather than waiting for the next scheduled 
imaging assessment. Any imaging modalities, if obtained and clinically indicated to assess 
response or progression, must be entered in the electronic data capture pages for evaluation of 
response or progression. 
Each lesion that is measured at baseline must be measured by the same method and when 
possible, the same local radiologist/physician throughout the study so that the comparison is 
consistent. If an off-schedule imaging assessment is performed because progression is suspected, 
subsequent imaging assessments should be performed in accordance with the original imaging 
schedule. 
Objective response (according to RECIST v1.1) should be confirmed by a repeat imaging 
assessment at least 4 weeks (28 days) after the initial response is recorded. Participants who 

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obtain a confirmation scan do not need to undergo the next scheduled tumor imaging if it is 
<4 weeks later; tumor imaging may resume at the subsequent scheduled imaging time point. 
If previous tumor imaging was obtained within 4 weeks prior to the date of discontinuation, then 
tumor imaging at treatment discontinuation is not necessary. In participants who discontinue 
study treatment without evidence of radiographic disease progression, tumor imaging must be 
performed until evidence of radiographic disease progression or until the start of new anti-cancer 
treatment, withdrawal of consent, death, or the end of the study, whichever occurs first. 
8.2.2. 
Survival Status  
Survival status will be assessed every 60 days (±7 days) beginning from the day of the last dose 
of study treatment until the participant withdrawals consent or death, whichever occurs first. 
Survival status may be requested more frequently around the time of a database lock. This 
information can be given by the participant or a family member. Information may also be 
obtained by any mechanism allowed per applicable regulations, such as telephone, email, public 
information, visit, or other. 
8.3. 
Safety Assessments  
8.3.1. 
Physical Examination  
A complete physical examination is required at screening and includes, at a minimum, general 
appearance of the following body systems: lymph node regions, mouth and throat, lungs, 
cardiovascular, abdomen, extremities (including muscular-skeletal system), neurological system, 
and skin. Clinically significant abnormal findings should be recorded as medical history. After 
the first dose of study treatment, new clinically significant abnormal findings should be recorded 
as AEs. During the treatment phase, a targeted/directed physical examination will be performed 
as specified in Table 1 and Table 3. Targeted examination includes, at a minimum, the following 
body systems: eyes; ear, nose, and throat; cardiovascular; abdominal and neurological 
examination. 
Body Measurements 
Height (measured at screening only) and body weight should be measured as indicated  in 
Table 1 and Table 3. The participant’s body weight should be measured and used to calculate the 
dose of study drug for infusion. If body weight is measured ≤7 days before the day of the 
planned study treatment, this result can be used for calculation of dose. 
8.3.2. 
Vital Signs  
Vital signs (including temperature, blood pressure, respiratory rate, and heart rate) are to be 
measured according to Table 1  and Table 3. The participant should be resting for ≥10 minutes 
before vital signs are measured. Temperature should be measured according to local practice. 
Within each visit, preferably the same equipment shall be used for vital sign measurements. On 
infusion days, vital signs should be assessed before the infusion start. 
8.3.3. 
Electrocardiograms  
For all participants, one 12-lead electrocardiogram (ECG) will be performed at screening, at the 
end of treatment visit, and as clinically indicated during the treatment period. All participants 

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should be resting for ≥10 minutes prior to obtaining the ECG. In case any irregularity (eg, 
vomiting or cough) occurs during the recording of the ECG, the ECG should be repeated. The 
ECG recordings should be locally evaluated by investigator (the investigator may delegate this 
task to a cardiologist, if applicable) in order to exclude any safety concerns. 
8.3.4. 
ECOG Performance Status  
ECOG performance status will be assessed by the investigator as indicated in Table 1 and 
Table 3 and scored per Table 8. 
Table 8: 
ECOG Performance Status 
Score  
Performance Status  
0 
Fully active, able to carry out all normal activity without restriction. 
1 
Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or 
sedentary nature, eg, light housework, office work. 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. 
Up and about more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 
4 
Completely disabled. Cannot carry out any self-care. Totally confined to bed or chair. 
5 
Dead. 
8.3.5. 
Eye Examination and Ocular Assessment  
Eye examination should be assessed by investigator as indicated in Table 1 (every visit except 
survival follow-up visit). The eye examination should include a visual inspection of the eye orbit 
and conjunctiva and control of normal eye movement. The participant should furthermore be 
asked about any ocular symptoms (eg, itchy eyes, sticky eyelids, eye secretion, blurry vision, 
etc.). 
An ocular assessment should be performed by an optometrist or ophthalmologist at screening for 
baseline evaluation, as indicated in Table 1 and Table 3. This assessment may also be performed 
as needed at unscheduled visits by the treating physician or delegate. The following assessments 
should be performed: visual acuity, Schirmer’s test, slit lamp, inspections of the conjunctivas and 
corneas including staining, intraocular pressure, and fundoscopy. A visual inspection of the eye 
orbit and conjunctiva and control of normal eye movement should also be performed. Clinically 
significant abnormal findings at baseline should be recorded as medical history. After the first 
dose of study treatment, new clinically significant abnormal findings should be recorded as AEs. 
Participants should be informed to contact their investigator or delegate immediately in case of 
any ocular symptoms appearing between tisotumab vedotin administration days and should be 
referred for a prompt ophthalmologist or optometrist evaluation (within 72 hours). 
8.3.6. 
Clinical Laboratory Assessments  
Laboratory assessments detailed in Table 9 should be obtained according to the schedule of 
assessments outlined in Table 1 and Table 3. All clinical laboratory tests will be performed 

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locally. This testing will include institutional standard tests for evaluating safety and making 
clinical decisions. Results of clinical laboratory tests are to be submitted to the central laboratory. 
Laboratory tests for screening should be performed ≤7 days prior to the first dose of study 
treatment. After Cycle 1, pre-dose laboratory procedures can be conducted ≤72 hours prior to 
dosing. Results will be reviewed by the investigator or qualified designee and found to be 
acceptable prior to each dose of study treatment. 
Additional local laboratory assessments not included in the assessment schedule, eg, needed for 
dosing decision, should be obtained and collected as required according to local labels and 
guidelines for topotecan, vinorelbine, gemcitabine, irinotecan, and pemetrexed and results 
submitted to the central laboratory. Also, unscheduled laboratory assessments may be obtained at 
the discretion of the investigator, eg, to be used as supportive information for an AE or for dose 
modifications or delays of the study treatment. For details on AE reporting of laboratory test 
abnormalities, refer to Section 8.4.2. 
Table 9: 
Laboratory Assessments 
Laboratory Assessments 
Parameters 
Hematology 
Hematocrit 
Red blood cell indices: 
MCH 
MCHC 
MCV 
%Reticulocytes 
WBC count with 
differential: 
Basophils 
Eosinophils 
Lymphocytes 
Monocytes 
Neutrophils 
Hemoglobin  
Platelet count 
RBC count 
Coagulation factors 
aPTT 
INR 
Fibrinogen 
Biochemistry 
ALT 
Calcium 
Magnesium 
Albumin 
C-reactive Protein 
Sodium 
Alkaline phosphatase 
Creatinine (GFR 
calculation) 
Total and direct 
bilirubin 
AST 
Glucose 
Uric acid 
blood urea nitrogen 
Lactate dehydrogenase 
Potassium 
eGFR 
Calculated eGFR (MDRD formula) 
Other Screening Tests 
HBsAg/HBV DNA, or HCVAb or RNA (where applicable) 
Pregnancy Testa 
Serum or urine beta-human chorionic gonadotropinb 
a. 
For participants of reproductive potential (see Section 10.4) 
b. Serum beta-hCG is required at screening for eligibility. Thereafter, serum or urine can be used unless urine 
pregnancy results cannot be confirmed as negative, or if required as per local regulations where applicable. 

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8.4. 
Adverse Events and Serious Adverse Events  
8.4.1. 
Adverse Event Definitions  
8.4.1.1. 
Definition of Adverse Event  
An AE is any untoward medical occurrence in a clinical study participant temporally associated 
with the use of a medicinal product, whether or not considered related to the medicinal product. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 
medicinal product. 
AEs (including laboratory abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible, rather than individual underlying signs and symptoms. When a 
clear diagnosis cannot be identified, each sign or symptom should be reported as a separate AE. 
8.4.1.2. 
Definition of Serious Adverse Event  
An SAE is defined as an AE that meets one of the following criteria: 
• Is fatal or life-threatening1 
• Results in persistent or significant disability/incapacity 
• Constitutes a congenital anomaly/birth defect 
• Is medically significant, ie, defined as an event that jeopardizes the participant or may 
require medical or surgical intervention to prevent one of the outcomes listed above. 
Medical and scientific judgment must be exercised in deciding whether an AE is 
“medically important”. 
• Requires inpatient hospitalization or prolongation of existing hospitalization2  
1. The term "life-threatening" in the definition of "serious" refers to an event in which the 
participant was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death if it was more severe. 
2. Hospitalizations for the following reasons should not be reported as SAEs: 
− Routine treatment or monitoring of the underlying disease, not associated with 
any deterioration in condition 
− Elective or pre-planned treatment for a pre-existing condition that is unrelated to 
the indication under study and has not worsened since signing the ICF 
− Social reasons and respite care in the absence of any deterioration in the 
participant’s general condition 
− Treatment on an emergency outpatient basis that does not result in hospital 
admission and involves an event not fulfilling any of the definitions of an SAE 
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8.4.1.3. 
Definition of AEs of Special Interest for Tisotumab Vedotin  
AESIs are defined as events (serious or non-serious) of scientific and medical concern specific to 
the sponsor’s product or program. Such events may require further investigation in order to 
characterize and understand them. Some AESIs require immediate reporting, as described in 
Section 8.4.2. AESIs are defined on the basis of an ongoing review of the safety data. The 
following AESIs for tisotumab vedotin are discussed further in the Investigator’s Brochure: 
• Ocular AEs 
• Bleeding AEs 
• Peripheral neuropathy AEs 
8.4.2. 
Adverse Event Reporting  
The sponsor has a legal responsibility to notify, as appropriate and according to local regulations, 
both the local regulatory authority and other regulatory agencies about the safety of the product 
under clinical investigation. Prompt notification of SAEs by the investigator to the sponsor is 
essential so that legal obligations and ethical responsibilities towards the safety of participants 
are met. 
The safety reporting period for all AEs is from study Day 1 (predose) through the EOT visit or 
30 days after the last drug administration, whichever is later. AEs that occur after the ICF is 
signed and prior to first study treatment dose should be reported as AEs if they were assessed by 
the investigator to be caused by a protocol-mandated procedure (ie, tumor biopsy or CT scan), 
including washout or discontinuation of prior medications. Any medical condition (signs, 
symptoms, and diagnosis) occurring prior to first study treatment dose should be recorded as 
medical history in the “Medical History & Pre-existing Conditions” form. Any medical history 
condition that worsens after the first dose of study treatment will be recorded as an AE. 
The following AEs must be reported to the sponsor within 24 hours: 
• All SAEs 
• All Ocular AEs regardless of grade 
• All events of overdose and/or medication errors with tisotumab vedotin whether 
associated with an AE or not. All events of overdose and/or medication errors with 
the comparator chemotherapy, only if associated with an AE 
• Any event of pregnancy (regardless of treatment arm) 
Completed safety reporting documents must be forwarded to the sponsor within 24 hours 
following one of these events:  
a. the participant visit at which such AE was reported, noted, or recognized 
b. the principal investigator’s or any investigator personnel’s receipt of the test results  
c. other information at, or from which, such development was reported, noted, or 
recognized. 
Study sites should make every effort to respond to follow-up queries from sponsor within 
3 working days. 

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In this study, progression of underlying malignancy is not reported as an AE or SAE. No 
individual IND safety reports will be submitted for progression of underlying malignancy. 
Progression of underlying malignancy will be evaluated as an efficacy endpoint. 
8.4.3. 
Follow-up of Adverse Events and Serious Adverse Events  
All AEs must be followed until they are resolved or until the end of treatment visit, whichever 
occurs first. However, AESIs qualifying for safety reporting and all SAEs (independent of 
causality) still ongoing after the end of treatment visit should be followed on a regular basis, 
according to the investigator’s clinical judgment, until the event has been resolved or until the 
investigator assesses it as chronic and all queries have been resolved. Only SAEs judged by the 
investigator as related to study treatment should be reported after the 30-day end of treatment 
visit. 
Assessment of all peripheral neuropathy cases (regardless of meeting criteria for safety 
reporting) will be performed every 60 days (by telephone contact) from the time of treatment 
discontinuation until one of the following criteria are met: 
• The event returns to baseline or to grade 1 
• The participant changes to another chemotherapeutic agent with known neurologic 
toxicity 
• The participant is considered lost to follow-up 
8.4.4. 
Diagnosis  
The diagnosis/underlying cause of an AE should be recorded rather than symptoms of the AE. If 
no diagnosis is available, each sign and symptom must be recorded as individual AEs. 
8.4.5. 
Suspected Unexpected Serious Adverse Reactions  
The sponsor will ensure that all relevant information about serious unexpected suspected adverse 
reactions (SUSARs) is recorded and reported as soon as possible, but within a maximum of 
15 days (fatal or life-threatening SUSARs within a maximum of 7 days) of first knowledge by 
the sponsor or designee, to the competent regulatory authorities, and/or to the ethics committee 
according to the applicable local regulatory requirements. Relevant follow-up information of 
fatal or life-threatening SUSARs will be communicated subsequently within an additional 
8 days. 
The investigator must be aware of local reporting regulations to the IEC/IRB. The sponsor will 
either supply the investigator with the reports which must be passed on to the IEC/IRB or report 
directly to the IEC/IRB, depending on local regulations. 
8.4.6. 
Pregnancy  
Any pregnancy in a study participant must be reported to the sponsor within 24 hours of learning 
of its occurrence. Pregnant study participants must immediately permanently discontinue trial 
treatment. The pregnancy should be followed up to determine outcome (including premature 
termination) and status of mother and child. The child should be followed up to approximately 
6 months of age. Pregnancy complications and elective terminations for medical reasons must be 

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reported as an AE or SAE. Spontaneous abortions must be reported as an SAE. Any SAE 
occurring in association with a pregnancy brought to the investigator’s attention after the 
participant has completed the study and considered by the investigator as possibly related to 
study treatment must be promptly reported to the sponsor. 
8.4.7. 
Pre-existing Condition  
In this study, a pre-existing condition (ie, a disorder present before the AE reporting period has 
started and noted on the Medical History & Pre-existing Conditions form) should not be reported 
as an AE. If a pre-existing condition worsens during the AE reporting period, the event must be 
reported as an AE. 
8.4.8. 
Disease Progression or Death  
Since progression of underlying malignancy is being assessed as an efficacy variable, it should 
not be reported as an AE or SAE. The terms “Disease Progression”, “Progression of Disease” or 
“Malignant Disease Progression” and other similar terms should not be used to describe an AE 
or SAE. However, clinical symptoms of progression may be reported as AEs or SAEs if the 
symptom cannot be determined as exclusively due to progression of the underlying malignancy 
or does not fit the expected pattern of progression for the disease under study. In addition, 
complications from progression of the underlying malignancy should be reported as AEs or 
SAEs. 
All deaths within 30 days of last dose, except death caused by disease progression, should be 
reported as SAEs. 
8.4.9. 
Unrelated Procedures  
Diagnostic and therapeutic non-invasive and invasive procedures, such as surgery, should not be 
reported as AEs. A medical condition for which an unscheduled procedure was performed, must 
however be reported if it meets the definition of an AE. For example, an acute appendicitis must 
be reported as the AE and not the appendectomy. 
8.4.10. 
Laboratory Test Abnormalities  
Any laboratory abnormality that induces clinical signs or symptoms, requires concomitant 
therapy, or requires changes in study treatment must be reported as an AE. The following 
laboratory test result abnormalities should be captured as AEs or SAEs, as appropriate: 
• Any laboratory test result abnormality that is clinically significant or meets the 
definition of an SAE 
• Any laboratory test result abnormality that requires the participant to have study drug 
discontinued or interrupted 
• Any laboratory test result abnormality that requires the participant to receive specific 
corrective therapy 
Whenever possible, a diagnosis, rather than a symptom, should be provided (eg, anemia instead 
of low hemoglobin). Laboratory abnormalities that meet the criteria for AEs must be followed 
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an abnormal laboratory or test result corresponds to a sign/symptom of an already reported AE, it 
is not necessary to separately record the laboratory/test result as an additional event. 
Note: A CTCAE grade 3 or 4 laboratory value abnormality does not automatically indicate an 
SAE. 
8.4.11. 
Information About Infusion-Related Reactions  
For all AEs with onset during or <24 hours after infusion of study drug, the investigator must 
assess whether the AE is considered caused by the infusion (ie, considered an IRR). 
8.5. 
Treatment of Overdose  
8.5.1. 
Overdose and Medication Errors  
For tisotumab vedotin dose administration, please refer to Section 6.1.1. For the purposes of this 
study, an overdose is defined as >10% of the prescribed tisotumab vedotin dose or ≥20% of any 
prescribed chemotherapy dose. No specific information is available on the treatment of overdose 
of tisotumab vedotin. There is currently no known antidote for an overdose of tisotumab vedotin. 
In the event of overdose, tisotumab vedotin or chemotherapy should be discontinued and the 
participant should be observed closely for signs of toxicity. Appropriate supportive treatment 
should be provided if clinically indicated. Notify the sponsor’s medical monitor as soon as they 
become aware of the overdose, to relay details of the overdose (e.g., exact amount of tisotumab 
vedotin administered, participant weight) and AEs, if any. 
If an AE is associated with (“results from”) the overdose of tisotumab vedotin, the AE should be 
reported as an SAE, even if no other seriousness criteria are met. If a dose of tisotumab vedotin 
meeting the protocol definition of overdose is taken without any associated clinical symptoms or 
abnormal laboratory results, the overdose is reported as a non-serious AE, using the terminology 
“accidental or intentional overdose without adverse effect.” All reports of overdose with and 
without an AE must be reported within 24 hours to the sponsor. 
8.6. 
Pharmacokinetics  
Blood samples for assessment of tisotumab vedotin and MMAE will be drawn in accordance 
with the PK assessment schedule (refer to Table 2). Three assays will be performed: 
• Detection of tisotumab vedotin (ie, conjugated antibody only) 
• Detection of total antibody (ie, conjugated and unconjugated antibody) 
• Detection of free MMAE in circulation 
• Samples will be used to evaluate the PK of tisotumab vedotin. Remaining samples 
collected for analyses of tisotumab vedotin plasma concentration may also be used to 
evaluate other safety, efficacy, or biomarker laboratory parameters. 
Note: Sites will be notified if prospective PK blood sample collection is no longer required 
during the course of the study. 

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8.7. 
Biomarkers  
Exploratory biomarker assessments may be performed on tumor tissues and/or whole blood 
samples, to expand on the understanding of pharmacodynamic effects and the mechanism of 
action of tisotumab vedotin, assess potential predictors of participant response to tisotumab 
vedotin, or further the understanding of TF biology and cervical cancer. Samples for exploratory 
biomarkers will be collected at protocol-specific time points as specified in Table 1 and Table 3. 
Biomarker assessments will not be used for participant selection. 
Biomarker analyses are dependent upon the availability of appropriate biomarker assays and 
clinical response rates. Biomarker analysis may be deferred or not performed, if during or at the 
end of the study, it becomes clear that the analysis will not have sufficient scientific value for 
biomarker evaluation, or if there are not enough samples or responders to allow for adequate 
biomarker evaluation. In the event the study is terminated early or shows poor clinical efficacy, 
completion of biomarker assessments is based on justification and intended utility of the data. 
8.7.1. 
Biomarker Assessments in Blood and Tumor Samples  
Biomarker assays may be performed on blood samples to address whether changes in circulating 
tumor DNA correlate with patient response and level of disease.  
Tissue biopsies may be assessed for specific pharmacodynamic, predictive, and prognostic 
biomarkers in the tumor. To characterize the malignancy and response to study treatment, 
biomarker assessments in tumor biospecimens may include measurements of tisotumab vedotin 
and its potential metabolites as well as characterization of the tumor microenvironment, drug 
target(s), tumor subtyping, profiling of somatic mutations and/or gene expression.  
Biomarker assessments may include: 
• Expression of TF protein. TF expression in the tumor will be explored in relation to 
clinical response. Other proteins related to tisotumab vedotin mechanism of action 
and cervical cancer (PD-L1 or other proteins) may also be explored in tumor biopsies 
by IHC or similar methods. 
• Tumor messenger RNA expression. RNA sequencing may be performed on tumor 
biopsies to determine TF RNA expression levels, and to evaluate expression of other 
genes associated with cervical cancer biology, response to tisotumab vedotin (eg, 
MDR1, MDR6), or markers of the immune microenvironment (eg PD-1, PD-L1, 
CD8). 
• Tumor DNA sequencing. Next generation sequencing (NGS) may be performed to 
evaluate DNA mutations, copy number variations, microsatellite instability, 
insertions, deletions, or rearrangements in genes associated with the mechanism of 
action of tisotumab vedotin or cervical cancer biology.  
8.7.2. 
Tumor Tissue Sample Collection  
Samples for biomarker analyses will be collected as specified in Table 1 and Table 3. Detailed 
instructions for tissue collection, processing and shipment are provided in the Laboratory 
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For the purposes of screening, the most recent archival tumor biopsy should be collected for 
biomarker analyses, preferentially within the last 2 years. If an adequate archival tumor biopsy 
less than 2 years old is not available, a fresh tumor biopsy should be collected before initiation of 
study treatment, if clinically feasible. If a fresh biopsy cannot be collected, the most recent 
archival tumor sample may be submitted, even if obtained more than 2 years prior to participant 
enrollment. Note that no tumor biopsy sample is required to be provided if the subject fails 
screening. 
An optional fresh biopsy collected at time of radiographic disease progression may be provided 
for biomarker analyses, if clinically feasible and if the participant provides consent for this 
procedure. 
If a tumor biopsy is collected per standard of care while the participant is on study (until 
treatment discontinuation), the FFPE block or unstained slides may be provided for biomarker 
analyses, if the participant provides consent for this procedure. 
Core needle and excisional biopsies, or resected tissues, formalin fixed and paraffin embedded, 
are acceptable. FFPE blocks are preferred to unstained slides. If unstained slides are provided, 
freshly cut serial sections are requested. Detailed instructions for tissue collection, processing 
and shipment are provided in the Laboratory Manual. 
If it is determined at any time before study completion that additional material is needed from a 
FFPE tumor sample for the successful completion of the protocol-specified analyses, the sponsor 
may request that additional material from existing samples. Also, based on emerging scientific 
evidence relating to a potential correlation between a biomarker and treatment efficacy or safety, 
the sponsor may request additional material from previously collected tumor samples. 
8.7.3. 
DNA/RNA Research  
DNA/RNA samples from the tumor may be analyzed to assess gene expression levels, mutations, 
copy number variations, microsatellite instability, insertions, deletions, and rearrangements in 
genes as described in previous biomarker sections.  
DNA/RNA samples may be used for research related to tisotumab vedotin or cervical cancer. 
8.7.4. 
Patient Reported Outcomes  
The following HRQOL questionnaires will be completed as described in Table 1 and Table 3. It 
is strongly recommended that the questionnaires be completed by the participant first upon 
arrival for a visit (ie, before any disease/treatment dialog with study nurse/treating physician or 
initiation of other preparations for the study treatment).  
EQ-5D-5L 
EQ-5D-5L is a standardized instrument developed by the EuroQol Group as a measure of 
HRQOL that can be used in a wide range of health conditions and treatments (Herdman 2011) 
(Rabin 2001). The EQ-5D-5L consists of a descriptive system and the EQ VAS. The descriptive 
system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression. The EQ VAS records the participant’s self-rated health on a vertical VAS. 
This can be used as a quantitative measure of health outcome that reflects the participant’s own 
judgment. The scores on these 5 dimensions can be presented as a health profile or can be 

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converted to a single summary index number (utility) reflecting preferability compared to other 
health profiles. 
EORTC-QLQ-C30 
The QLQ-C30 is a validated questionnaire developed by the European Organization for Research 
and Treatment of Cancer (EORTC) to assess the quality of life of participants with cancer in 
multicultural clinical research settings (Aaronson 1993). 
EORTC-QLQ-CX24 
The EORTC-QLQ-CX24 is a validated questionnaire developed by the EORTC to assess the 
quality of life in patients who are treated for cervical cancer both in clinical studies and in 
clinical practice (Greimel 2006). 
8.8. 
Immunogenicity Assessments  
8.8.1. 
Evaluations  
Venous blood samples will be drawn for central analysis of ADAs at the time points shown in 
Table 2. Samples collected for ADA to tisotumab vedotin may also be used to evaluate safety, 
efficacy, or biomarker laboratory parameters to address concerns arising during the study. 
8.8.2. 
Immunogenicity Assessments  
Antibodies to tisotumab vedotin will be evaluated in serum samples collected from all 
participants according to the visit schedule (Table 2). 
Serum samples will be screened for antibodies binding to tisotumab vedotin and the titer of 
confirmed positive samples will be reported. Other analyses may be performed to verify the 
stability of antibodies to tisotumab vedotin or further characterize the immunogenicity of 
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9. 
STATISTICAL CONSIDERATIONS  
9.1. 
Statistical Hypotheses  
The overall type I error for this study is controlled at 5% (2-sided) for the statistical hypotheses 
on the primary endpoint, OS, and the key secondary endpoints, PFS and ORR, by using a 
hierarchical group sequential procedure (GSP) (Maurer 2013). One interim analysis (IA) and one 
final analysis (FA) are planned, and the timing of the analyses will be determined by the OS 
endpoint. 
9.2. 
Sample Size Determination  
Approximately 482 participants will be randomized in a 1:1 ratio to one of the 2 study arms. No 
crossover between treatment arms is permitted. 
This sample size is determined to provide sufficient power to demonstrate superiority of the 
tisotumab vedotin arm against the control arm based on the primary endpoint OS. Specifically, 
this sample size, with a total number of approximately 336 OS events, provides an overall power 
of 90% for the hypothesis testing on OS at a 2-sided 5% significance level to detect an HR ≠ 1 
when the true HR is 0.7, with the following assumptions: 
• median OS of 12.9 months in the tisotumab vedotin arm 
• median OS of 9 months in the chemotherapy arm 
• drop-out rate of 5% per year 
• an IA at approximately 75% (252) of the total number of OS events using the Lan 
deMets (O’Brien Fleming) boundary (Lan 1983) 
• accrual duration of approximately 23 months with at least 12 months of follow-up 
• 1:1 randomization ratio 
The IA and FA on OS are estimated to occur at approximately 27 and 35 months after the first 
participant is randomized into the study.  
At the OS IA and FA, it is estimated that the number of PFS events will be approximately 413 
and 457, respectively, which will provide an overall power of 95% at a 2-sided 5% level of 
significance assuming an HR of 0.7 with a median PFS of 4.3 months in the tisotumab vedotin 
arm and a median PFS of 3 months in the control arm.  
For ORR, it is estimated that all 482 participants will be fully randomized into the study, based 
on the assumed accrual, and have at least 2 post-baseline scans at the OS IA and FA timings. 
This provides an overall power of approximately 99% at a 2-sided 5% level of significance 
assuming an ORR of 25% for the tisotumab vedotin arm and a 10% ORR for the control arm. 
9.3. 
Populations for Analyses  
Intent-to-treat (ITT) analysis set: This analysis set includes all participants who are randomized 
into the study. Participants will be included in the treatment group assigned at randomization 
regardless of the actual treatment received. The primary analysis of the efficacy endpoints will 

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be based on the ITT analysis set. Demographics and baseline characteristics will also be 
summarized on the ITT analyses set. 
Safety analysis set: This analysis set includes all randomized participants who received any 
amount of the study treatment. Participants will be evaluated by the treatment actually received. 
Analyses on treatment exposure and safety will be based on the safety analysis set. 
Additional analysis sets may be defined in the Statistical Analysis Plan (SAP). 
9.4. 
General Considerations  
The SAP will be finalized prior to the database lock for primary analyses, and it will include a 
more technical and detailed description of the statistical analyses described in this section. This 
section is a summary of the planned statistical analyses on the main study endpoints including 
primary and key secondary endpoints. 
9.4.1. 
Responsibility for Analyses/In-house Blinding  
The statistical analysis of the data from this study is the responsibility of the sponsor. 
The randomization list will be prepared by the RTSM system vendor. Although this is an open 
label study, to maintain trial integrity, analyses or summaries by randomized treatment or actual 
treatment assignment will be limited and documented while the study is ongoing and before the 
database lock for primary analyses. 
Results of the planned OS, PFS, and ORR interim analyses will be provided to the IDMC by an 
external independent vendor. Additional details will be provided in a separate document. 
9.5. 
Efficacy Analyses  
The primary analyses on efficacy endpoints will be analyzed using the ITT analysis set. 
Stratified primary analyses will use stratification factors (ECOG, prior bevacizumab, and prior 
anti-PD-[L]1 therapy) with values as employed in the randomization. The stratification factor of 
region will not be included in the stratified primary analyses to reduce sparse strata. 
9.5.1. 
Overall Survival  
OS is defined as the time from the date of randomization to the date of death due to any cause. 
OS is the primary endpoint of this trial. 
The difference in OS between the treatment and control arms will be assessed by the stratified 
log-rank test. The 2-sided p-value corresponding to the test of superiority of tisotumab vedotin 
over chemotherapy (control) will be presented. The estimated HR and its 95% CI from the 
stratified Cox model will be presented. The median OS will be estimated using the Kaplan-Meier 
(KM) method and will be presented along with estimated KM curves and the corresponding 95% 
CI by treatment arm. 
In the absence of confirmation of death, survival time will be censored at the last date the 
participant is known to be alive. 

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9.5.2. 
Progression-Free Survival Assessed per Investigator  
PFS per investigator is defined as the time from the date of randomization to the first 
documentation of disease progression per RECIST v.1.1 by the investigator, or to date of death 
due to any cause, whichever occurs earlier. 
PFS will be analyzed using the same methods as described for the primary analyses on OS. In the 
primary analysis on PFS, participants without evidence of radiographic disease progression or 
death will be censored at the date of the last adequate tumor assessment prior to data cut-off date 
or the start of new anti-cancer therapy. Participants with disease progression or death that occur 
after 2 or more missed scans would be censored at the last adequate tumor assessment prior to 
the missed scans. Participants without post-baseline scan data would be censored at the day of 
randomization. 
9.5.3. 
Confirmed Objective Response Rate as Assessed by Investigator  
Confirmed objective response rate is defined as the proportion of participants with a confirmed 
CR or partial response (PR) per RECIST v.1.1. 
ORR will be analyzed using a Cochran-Mantel-Haenszel chi-squared test. The common odds 
ratio across strata will be estimated with its 95% CI and 2-sided p-value for testing of superiority 
of tisotumab vedotin over chemotherapy. 
In the primary analysis of ORR, participants without at least two post-baseline tumor 
assessments will be considered to be non-responders. 
9.5.4. 
Health-related Quality of Life (HRQOL)  
Results of the EQ-5D-5L index based on the UK Value Set, EQ-5D VAS, EORTC-QLQ-C30, 
and EORTC-QLQ-CX24 will be summarized. Longitudinal and descriptive data analysis will be 
used to evaluate patient-reported outcomes. Further details on these analyses will be provided in 
the statistical analysis plan. 
9.5.5. 
Duration of Response and Time to Response  
DOR and TTR will be summarized descriptively by treatment group using the Kaplan-Meier 
approach. Only participants with a confirmed CR or PR will be included in these analyses. 
9.5.6. 
Exploratory Analyses  
The relationship between TF expression and efficacy endpoints may be explored. Relationships 
and associated data that are determined to be of interest will be summarized. Biomarker data, 
PK, and ADA incidence will be summarized descriptively. Details will be described separately.  
9.5.7. 
Testing Strategy  
Hypothesis testing will be performed on the primary endpoint OS and two key secondary 
efficacy endpoints, PFS and ORR, while controlling the overall Type I error rate of 5% (2-sided) 
using a hierarchical approach with group sequential testing (Maurer 2013). 
The endpoints are tested in the hierarchical order as follows: OS first, then PFS, and finally 
ORR. Hypothesis testing starts with OS and will only proceed to the hypothesis testing on the 

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next endpoint, PFS, when the efficacy boundary is crossed for OS at the first time (IA or FA). 
Similarly, the hypothesis testing on ORR will only occur after the efficacy boundary is crossed 
for PFS.  
For OS, the Lan DeMets (O’Brien-Fleming) spending function will be used (Lan 1983). With 
approximately 252 and 336 events estimated to occur at the IA and FA respectively, the OS will 
be tested at a 2-sided nominal 0.019/0.044 level at the IA/FA corresponding to a HR boundary of 
0.75/0.80. 
For PFS, the Lan DeMets (Pocock) spending function will be used (Lan 1983). With 
approximately 413 and 457 events estimated to occur at the OS IA and FA respectively, the PFS 
will be tested at a 2-sided nominal 0.047/0.025 level at the IA/FA corresponding to an HR 
boundary of 0.822/0.811.  
For ORR, it is estimated that all 482 participants will be fully randomized into the study and 
have at least two post-baseline scans by the OS IA at 27 months. The ORR will be tested at 
2-sided 5% level corresponding to an odds ratio boundary of 1.67. 
For hypothesis testing on all endpoints, the actual nominal significance level to be applied will 
be adjusted to reflect the actual number of events realized at the time of the IA/FA using the 
specified spending function for each endpoint. The overall type 1 error for the 3 key endpoints, 
OS, PFS, and ORR, is controlled at a 2-sided 5% level using the approach of Maurer and Bretz 
(Maurer 2013). 
9.6. 
Safety Analyses  
Safety analyses will be performed on the safety analysis set. 
9.6.1. 
AEs  
An overview of AEs will provide a tabulation of the number and incidence of all 
treatment-emergent adverse events (TEAEs), treatment-related TEAEs, grade 3 and higher 
TEAEs, treatment-emergent SAEs, treatment-related treatment-emergent SAEs, deaths, TEAEs 
leading to dose modification, and TEAEs leading to study treatment discontinuation. A TEAE is 
defined as a newly occurring or worsening AE after the first dose of study treatment and with 
onset date on or before 30 days after the last dose of study treatment. 
AEs will be listed and summarized by Medical Dictionary for Regulatory Activities (MedDRA), 
system organ class, preferred term, severity, and relationship to study drug. In the event of 
multiple occurrences of the same AE with the same preferred term in one participant, the AE will 
be counted once as the occurrence. The incidence of AEs will be tabulated by preferred term and 
treatment group. AEs leading to discontinuation of study drug will be summarized and listed in 
the same manner. 
The following groups of TEAEs will be summarized: 
• All TEAEs 
• Grade 3 to 5 TEAEs 
• Treatment-emergent SAEs 
• Treatment-related TEAEs 

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• Treatment-related grade 3 to 5 TEAEs 
• Treatment-related treatment-emergent SAEs 
• TEAEs leading to dose reduction 
• TEAEs leading to dose interruption 
• TEAEs leading to dose delay 
• TEAEs leading to study drug discontinuation 
• Grade 5 TEAEs 
• Treatment-emergent AESIs 
• Treatment-emergent ocular AEs 
• Treatment-emergent bleeding AEs  
• Treatment-emergent peripheral neuropathy AEs  
Analyses of AEs will be summarized descriptively. Details will be specified in the SAP. 
9.6.2. 
Safety Laboratory Tests, Vital Signs, and ECG Parameters  
Continuous measures such as safety laboratory tests and vital signs will be summarized 
descriptively. Summary statistics for baseline, on-treatment, and change from baseline values 
will be summarized by treatment group. For safety laboratory parameters, shift tables from 
baseline based on CTCAE grading will be provided. For 12-lead ECG parameters, only a listing 
will be generated. 
9.7. 
Interim Analyses  
One interim efficacy analysis is planned when approximately 252 (75%) of the total expected 
336 OS events occur. The IDMC will evaluate the overall safety and efficacy data at the interim 
analysis to make recommendations regarding whether to terminate or continue the trial. Overall 
type I error for OS will be controlled using the O’Brien-Fleming spending function (Lan 1983). 
More details regarding the interim analysis will be described in the SAP. 
9.8. 
Trial Governance and Oversight  
9.8.1. 
Independent Data Monitoring Committee (IDMC)  
An IDMC, consisting of members who are external and independent of the sponsor study team, 
will be formed to monitor the safety of participants participating in this study on a periodic basis, 
review safety and efficacy data from this study as per planned analyses, and make 
recommendations to the sponsor. The IDMC will consist of a minimum of 3 physicians with 
appropriate disease area qualifications and a statistician who will be a non-voting member of the 
committee. 
Additional details on the IDMC will be described in a separate IDMC charter. 

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS  
10.1. 
APPENDIX 1: Regulatory, Ethical, and Study Oversight Considerations  
10.1.1. 
Protocol Amendments  
Neither the investigator nor the sponsor will modify this protocol without a formal amendment 
by the sponsor. All protocol amendments must be issued by the sponsor and signed and dated by 
the investigator. Protocol amendments must not be implemented without prior IEC/IRB 
approval, or when the relevant competent authority has raised any grounds for non-acceptance, 
except when necessary to eliminate immediate hazards to the participants, in which case the 
amendment must be promptly submitted to the IEC/IRB and relevant competent authority. 
Documentation of amendment approval by the investigator and IEC/IRB must be provided to the 
sponsor. When the change(s) involve(s) only logistic or administrative aspects of the trial, the 
IRB (and IEC where required) only needs to be notified. 
During the course of the trial, in situations where a departure from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the appropriate sponsor 
representative (see contact information page[s] provided separately). Except in emergency 
situations, this contact should be made before implementing any departure from the protocol. In 
all cases, contact with the sponsor must be made as soon as possible to discuss the situation and 
agree on an appropriate course of action. The data recorded in the eCRF and source documents 
will reflect any departure from the protocol, and the source documents will describe this 
departure and the circumstances requiring it. 
10.1.2. 
Regulatory Approval/Notification  
This protocol and any amendments must be submitted to the appropriate regulatory authorities in 
each respective country, if applicable. A trial may not be initiated until all local regulatory 
requirements are met. 
10.1.3. 
Participant Identification, Enrollment, and Screening Logs  
The investigator agrees to assign a unique participant identification to protect the participant’s 
identity and to permit easy identification of each participant during and after the trial. All reports 
and communications relating to the trial will identify participants by the unique participant 
identifiers and year of birth or age. 
The investigator must complete a participant screening and enrollment log, which reports on all 
participants who consent to be on trial, those who are screened, screen failures, and those who 
meet eligibility for inclusion in the trial. The participant identification log will be treated as 
confidential and will be filed by the investigator in the site file. The screening and enrollment 
logs will be reviewed by the sponsor or designee for completeness. 
10.1.3.1. Participant Identification Card  
After signing the ICF, it is recommended that all participants should be given participant 
identification cards by the site identifying them as participants in a clinical trial. The card should 

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contain trial site contact information (including direct telephone numbers) to be utilized in the 
event of an emergency. 
10.1.4. 
Ethics  
10.1.4.1. Trial-Specific Design Considerations  
Potential participants will be fully informed of the risks and requirements of the trial and, during 
the trial, participants will be given any new information that may affect their decision to continue 
participation. Only participants who are fully able to understand the risks, benefits, and potential 
AEs of the trial, and provide their consent voluntarily, will be enrolled. 
The total blood volume to be collected is considered to be within the normal range allowed for 
this participant population over the time frame of the trial. 
10.1.4.2. Regulatory Ethics Compliance  
Investigator Responsibilities 
The investigator is responsible for ensuring that the trial is performed in accordance with the 
protocol, current ICH guidelines on GCP, and applicable regulatory and country-specific 
requirements. 
This study will be conducted in accordance with the Note for Guidance on Good Clinical 
Practice (ICH Harmonised Tripartite Guideline E6 [R2]; FDA CFR [21 CFR § 50, 56, 312]), 
Declaration of Helsinki (Brazil 2013), and all applicable regulatory requirements. GCP is an 
international ethical and scientific quality standard for designing, conducting, recording, and 
reporting trials that involve the participation of human participants. Compliance with this 
standard provides public assurance that the rights, safety, and well-being of trial participants are 
protected, consistent with the principles that originated in the Declaration of Helsinki, and that 
the trial data are credible. 
Independent Ethics Committee or Institutional Review Board 
This trial will be undertaken only after the IEC/IRB has given full approval of the final protocol, 
amendments (if any, excluding the ones that are purely administrative, with no consequences for 
participants, data, or trial conduct), the ICF, applicable recruiting materials, and participant 
compensation programs, and the sponsor has received a copy of this written approval. This 
approval letter must be dated and must clearly identify the IEC/IRB and the documents being 
approved. 
Approval for the collection of samples for exploratory and DNA/RNA research and for the 
corresponding ICF must be obtained from the IEC/IRB as required by local regulations. 
Approval for the protocol can be obtained independent of this research component. 
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for participants, data, or trial conduct), the amendment and applicable ICF 
revisions must be submitted promptly to the IEC/IRB for review and written approval before 
implementation of the change(s) unless the amendment is issued to eliminate immediate hazards 
to trial participants. 
Where applicable, interim reports on the trial and/or review(s) of trial progress will be submitted 
by the investigator to the IEC/IRB at intervals stipulated in its guidelines. 

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At the end of the trial, the investigator (or sponsor where required) will notify the IEC/IRB about 
the trial completion. 
10.1.4.3. Return of Exploratory Research Data to Participants and Investigators  
Exploratory biomarker research is not conducted under standards appropriate for the return of 
data to participants or investigators. In addition, the sponsor cannot make decisions as to the 
clinical significance of any findings resulting from exploratory research. Therefore, exploratory 
research data will not be returned to participants or investigators, unless required by law or local 
regulations. Privacy and confidentiality of data generated in the future on stored samples will be 
protected by the same standards applicable to all other clinical data. 
10.1.5. 
Biospecimen Repository  
In the US only, for participants who provide additional consent, remaining de-identified unused 
blood and/or tissue will be retained by Seagen Inc and used for future research, including but not 
limited to the evaluation of targets for novel therapeutic agents, the biology of ADC sensitivity 
and resistance mechanisms, and the identification of biomarkers of ADCs. Blood and tissue 
samples donated for future research will be retained for a period of up to 25 years. If additional 
consent is not provided, any remaining biological samples will be destroyed after the study has 
been completed and all applicable regulatory obligations have been met. 
10.1.6. 
Regulatory and Ethical Considerations/Statement of Compliance  
• This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines 
• Applicable ICH Good Clinical Practice (GCP) Guidelines 
• Applicable laws and regulations 
• The protocol, protocol amendments, ICF, Investigator’s Brochure, and other relevant 
documents (eg, advertisements) must be submitted to an IRB/IEC by the investigator 
and reviewed and approved by the IRB/IEC before the study is initiated.  
• Any amendments to the protocol will require IRB/IEC approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants.  
• The sponsor may terminate the study at any time. The IRB/IEC must be advised in 
writing of study completion or early termination. 
• The investigator will be responsible for the following: 
• Providing the following to the IRB/IEC in accordance with the requirements, policies, 
and procedures established by the IRB/IEC: 
− Protocol and amendments 
− Informed consent document and updates 

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− Investigator’s Brochure and updates 
− Relevant curricula vitae, if required 
− Required safety and SAE reports 
− Any additional submissions required by the site’s IRB/IEC 
• Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations 
• The investigator must provide the following documentation to the sponsor or its 
designee: 
• The IRB/IEC periodic (eg, quarterly, annual) re-approval of the protocol. 
• The IRB/IEC approvals of any amendments to the protocol or revisions to the 
informed consent document. 
• The IRB/IEC receipt of safety and SAE reports, as appropriate. 
10.1.7. 
Financial Disclosure  
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. 
10.1.8. 
Clinical Trial Agreement  
Payments by the sponsor to investigators and institutions conducting the trial, requirements for 
investigators’ insurance, the publication policy for clinical trial data, and other requirements are 
specified in the clinical trial agreement. 
10.1.9. 
Investigator Information  
The contact information and qualifications of the principal investigator and subinvestigators and 
name and address of the research facilities are included in the investigator file. 
10.1.10. Informed Consent Process  
The investigator is responsible for presenting the risks and benefits of study participation to the 
participant in simple terms using the IRB/IEC approved informed consent document and for 
ensuring participants are re-consented when the informed consent document is updated during 
the study, if required. The investigator will ensure that written informed consent is obtained from 
each participant, or legally authorized representative, if applicable to this study, by obtaining the 
signature and date on the informed consent document prior to the performance of protocol 
evaluations or procedures. 
If informed consent is obtained from a legally authorized representative for a participant who is 
unable to provide informed consent at study entry (if applicable), but the participant is later able 

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to provide informed consent, the investigator must obtain written informed consent from the 
participant. 
The ICFs that are used must be approved by the reviewing IEC/IRB and be in a language that the 
participant can read and understand. The ICF should be in accordance with principles that 
originated in the Declaration of Helsinki 2013, current ICH guidelines, applicable regulatory 
requirements, and sponsor policy. 
It is the personal responsibility of the investigator or an authorized member of the trial-site 
personnel to explain to potential participants the aims, methods, reasonably anticipated benefits, 
and potential hazards of the trial, and any discomfort participation in the trial may entail. 
Participants will be informed that their participation is voluntary and that they may withdraw 
consent to participate at any time without justifying the reason. They will be informed that 
choosing not to participate will not affect the care the participant will receive for the treatment of 
their disease. Finally, they will be told that the investigator will maintain a participant 
identification register for the purposes of long-term follow-up if needed and that their records 
may be accessed by health authorities and authorized sponsor personnel without violating the 
confidentiality of the participant, to the extent permitted by the applicable laws or regulations. 
By signing the ICF, the participant is authorizing such access and agrees to allow their trial 
physician to re-contact the participant for the purpose of obtaining consent for additional safety 
evaluations, including scans, if needed. 
The participant will be given sufficient time to read the ICF and the opportunity to ask questions. 
After this explanation and before entry into the trial, consent should be appropriately recorded by 
means of the participant's personally dated signature. After having obtained the consent, a copy 
of the ICF must be given to the participant. 
Where required, a separate consent will be used for long-term retention of remaining samples for 
additional exploratory research (Refer to Section 10.1.5). 
10.1.11. Data Protection  
10.1.11.1. Study Documentation, Privacy and Records Retention  
To protect the safety of participants in the study and to ensure accurate, complete, and reliable 
data, the investigator will keep records of laboratory tests, clinical notes, and participant medical 
records in the participant files as original source documents for the study. If requested, the 
investigator will provide the sponsor, its licensees and collaborators, applicable regulatory 
agencies, and applicable IRB/IEC with direct access to original source documents or certified 
copies. 
Records containing participant medical information must be handled in accordance with local 
and national laws, rules, and regulations and consistent with the terms of the participant 
authorization contained in the informed consent document for the study (the Authorization). Care 
should be taken to ensure that such records are not shared with any person or for any purpose not 
contemplated by the Authorization. Furthermore, case report forms and other documents to be 
transferred to the sponsor should be completed in strict accordance with the instructions provided 
by the sponsor, including the instructions regarding the coding of participant identities. 

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In compliance with local and/or regional regulations, this trial may be registered and trial results 
may be posted on public registries, such as ClinicalTrials.gov. 
10.1.12. Data Quality Assurance  
10.1.12.1. Monitoring  
The sponsor or delegate will use a combination of remote and on-site monitoring to monitor this 
trial. The sponsor or delegate will perform on-site monitoring visits as frequently as necessary. 
The monitor will record dates of the visits in a trial-site visit log that will be kept at the trial-site. 
The first post-initiation visit will be made as soon as possible after enrollment has begun. At 
these visits, the monitor will compare the data entered into the eCRFs with the hospital or clinic 
records (source documents). The nature and location of all source documents will be identified to 
ensure that all sources of original data required to complete the eCRF are known to the sponsor 
and trial-site personnel and are accessible for verification by the sponsor trial-site contact. If 
electronic records are maintained at the trial site, the method of verification must be discussed 
with the trial-site personnel. 
Direct access to source documentation (medical records) must be allowed for the purpose of 
verifying that the data recorded in the eCRF are consistent with the original source data. Findings 
from this review of eCRFs and source documents will be discussed with the trial-site personnel. 
The sponsor expects that, during monitoring visits, the relevant trial-site personnel will be 
available, the source documentation will be accessible, and a suitable environment will be 
provided for review of trial-related documents. The monitor will speak with the investigator on a 
regular basis during the trial to provide feedback on the trial conduct. 
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during 
these remote contacts, trial-site personnel will be available to provide an update on the progress 
of the trial at the site. 
10.1.13. Source Documents  
At a minimum, source documentation must be available for the following to confirm data 
collected in the eCRF: participant identification, eligibility, and trial identification; trial 
discussion and date of signed informed consent; dates of visits; results of safety and efficacy 
parameters as required by the protocol; record of all AEs and follow-up of AEs; concomitant 
medication; drug receipt/dispensing/return records; trial drug administration information; and 
date of trial completion and reason for early discontinuation of trial drug or withdrawal from the 
trial, if applicable. In addition, the author of an entry in the source documents should be 
identifiable. 
At a minimum, the type and level of detail of source data available for a participant should be 
consistent with that commonly recorded at the trial site as a basis for standard medical care. 
Specific details required as source data for the trial will be reviewed with the investigator before 
the trial and will be described in the monitoring guidelines (or other equivalent document). 
10.1.14. Study and Site Start and Closure  
The sponsor reserves the right to close a site or terminate the trial at any time for any reason at 
the sole discretion of the sponsor. Sites will be closed upon trial completion. 

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The investigator may initiate site closure at any time, provided there is reasonable cause and 
sufficient notice is given in advance of the intended termination. 
Reasons for early closure of a site by the sponsor or investigator include but are not limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the 
IEC/IRB or local health authorities, the sponsor's procedures, or ICH Good Clinical 
Practice guidelines 
• Inadequate recruitment of participants by the investigator 
• Discontinuation of further tisotumab vedotin development 
• If the development of the tisotumab vedotin is discontinued, or study closure is 
necessary, the sponsor will ensure provisioning of post-study treatment for ongoing 
study participants 
10.1.15. Publication Policy  
The publication policy for clinical data from this trial can be found within the Clinical Trial 
Agreement. 
10.1.16. Registration of Clinical Trials and Disclosure of Results  
In compliance with local and/or regional regulations, this trial may be registered and trial results 
may be posted on public registries, such as ClinicalTrials.gov. 
 
 

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10.2. 
APPENDIX 2: Clinical Laboratory Tests  
Please refer to Section 8.3.6, Table 1 and Table 3. 
 
 

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10.3. 
APPENDIX 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting  
Please refer to Section 8.4. 
 
 

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10.4. 
APPENDIX 4: Definition of Reproductive Potential and Guidance on 
Contraception  
In this study, participants are considered to have reproductive potential, UNLESS they are 
post-menopausal or permanently sterile. 
• A post-menopausal state is defined as no menses in participants >45 years of age, for 
12 months without an alternative medical cause. A high follicle-stimulating hormone 
(FSH) level in the post-menopausal range should be used to confirm a post-
menopausal state in participants not using hormonal contraception or hormonal 
replacement therapy. However, in the absence of 12 months of amenorrhea, a single 
FSH measurement is insufficient. 
• Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and 
bilateral oophorectomy. 
All participants must agree not to donate eggs (ova, oocytes) for the purpose of assisted 
reproduction during the study and for 6 months after receiving the last dose of study treatment. 
Participants of reproductive potential must agree to use adequate contraception during and for 
6 months after the last study treatment administration. Adequate contraception is defined as 
highly effective methods of contraception (Table 10). Birth control methods are considered 
highly effective if they have a failure rate of <1% per year, when used consistently and correctly. 
 
 

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Table 10: 
Acceptable Methods of Contraception 
Participants who are of childbearing potentiala who are sexually active in a way that could lead to pregnancy may 
choose to use complete abstinence*, if consistent with the participant’s preferred lifestyle, OR any TWO of the 
following methods: 
● Hormonal methods of contraception associated with inhibition of ovulation  
● Intrauterine device with failure rate <1% 
● Tubal ligation 
● Vasectomy (at least 90 days from the date of surgery with a semen analysis documenting azoospermia) 
● A barrier method (male or female condom with or without spermicide, cervical cap with or without spermicide, 
diaphragm with or without spermicide) 
*Complete abstinence is defined as abstinence starting from the time of informed consent and continuing 
throughout the study and for at least 6 months after the final dose of study drug 
a. 
A person of childbearing potential is defined as anyone born female who has experienced menarche and 
who has not undergone surgical sterilization (eg, hysterectomy, bilateral salpingectomy, bilateral 
oophorectomy) or has not completed menopause. Menopause is defined clinically as 12 months of 
amenorrhea in a person born female over age 45 years in the absence of other biological, physiological, or 
pharmacological causes. 
Unacceptable Methods of Contraception 
● Periodic abstinence 
● No method 
● Withdrawal 
● Rhythm 
● Spermicide only 
● Progestin-only pills 
● Concomitant use of female and male condoms 
Tables adapted from “Recommendations related to contraception and pregnancy testing in clinical trials.” advisory 
non-binding guidance represented at the Clinical Trials Facilitation Group meeting, Rome 2014. (UK MHRA 
2014). 
 
 

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10.5. 
APPENDIX 5: Genetics  
Not applicable. 
 
 

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10.6. 
APPENDIX 6: Liver Safety: Potential Drug-Induced Liver Injury  
The observation of the critical importance of altered liver function has been referred to 
informally as Hy’s Law (Reuben 2004). Hy’s Law can be used to estimate severity and the 
likelihood that a study drug may cause an increased incidence of severe hepatotoxicity. 
The absence of hepatotoxicity in clinical trials provides a limited predictive value for potential 
hepatotoxicity in the clinical setting(s) being studied. However, finding 1 Hy’s Law case in 
clinical trials is ominous; finding 2 cases is highly predictive of a potential for severe drug-
induced liver injury (DILI). 
Definition 
Briefly, potential Hy’s Law cases include the following 3 components: 
1. Aminotransferase (ALT and/or AST) elevation >3 x ULN 
AND 
2. Total bilirubin >2 x ULN, without initial findings of cholestasis (ie, elevated serum 
alkaline phosphatase), 
AND 
3. No other immediately apparent possible causes of aminotransferase elevation and 
hyperbilirubinemia, including, but not limited to, viral hepatitis, pre-existing chronic or 
acute liver disease, or the administration of other drug(s) known to be hepatotoxic. 
Reporting Requirements 
Any potential Hy’s Law case should be handled as a suspected unexpected serious adverse 
reaction (SUSAR) associated with the use of the drug and reported promptly to the 
sponsor. 
Reporting should include all available information and should initiate close follow-up until 
complete resolution of the problem and completion of all attempts to obtain supplementary data. 
Follow-up for Abnormal Laboratory Results Suggesting Potential DILI 
In general, an increase of serum ALT or AST to >3x ULN should be followed by repeat testing 
within 48 to 72 hours of serum ALT, AST, alkaline phosphatase, and total bilirubin, to confirm 
the abnormalities and to determine whether they are worsening. 
Appropriate medical assessment should be initiated to investigate potential confounding factors 
and alternative causes of hepatotoxicity. During this investigation, study drug should be 
withheld. 
 
 

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10.7. 
APPENDIX 7: Dose Modifications for the Chemotherapy Arm  
Dose modifications for the chemotherapy arm should always be performed as per local labeling 
or institutional guidelines. The following section provides toxicity management 
recommendations for selected AEs that are characteristic for the investigator’s choice 
chemotherapy agents. For other chemotherapy-related AEs that are not specifically addressed in 
the following sections, the general approach for ≥ grade 3 TEAEs is to hold chemotherapy until 
resolution of the event to ≤ grade 1 or baseline, and to reduce by 1 dose level on resumption of 
treatment. 
The starting doses specified in Section 6.1.2 should not be modified. Treatment may be delayed 
to allow for resolution of toxicity to pretreatment, baseline levels. The treating investigator 
should contact the sponsor to discuss the case of any participant whose treatment has been 
delayed beyond what is specified in local labeling or institutional guidelines.  
Dose adjustments at the start of a subsequent cycle should be based on nadir observed 
hematologic counts or maximum nonhematologic toxicity from the preceding cycle of therapy. 
Treatment may be delayed to allow sufficient time for recovery. Upon recovery, participants may 
be retreated using guidelines in the following subsections. Missed doses of chemotherapy will 
not be made up. 
 

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10.7.1. 
Recommended Dose Modifications for Topotecan  
The starting dose for topotecan is 1.0 mg/m2 or 1.25 mg/m2 × 5 days, every 21 days.  
Toxicity 
Dose Modification 
ANC ≤1000/mm3 or 
Platelet count of ≤100,000/mm3 or 
Hemoglobin <9.0 g/dL or 
Serum creatinine >1.5 mg/dL 
Delay next cycle of topotecan until hematologic 
or renal recovery. No dose reduction unless 
criteria below are met 
ANC <500/mm3 in preceding cycle 
Permanently reduce topotecan dose to 0.75 
mg/m2 or administer prophylactic G-CSF during 
subsequent cycles 
Platelets <25,000/mm3 in preceding cycle 
Permanently reduce topotecan dose to 0.75 
mg/m2 
Creatinine clearance 20 mL/min to 39 mL/min in preceding 
cycle 
Permanently reduce topotecan dose to 0.75 
mg/m2 
Special safety considerations for topotecan: 
• Topotecan-induced neutropenia can lead to neutropenic colitis, which can be fatal. In 
participants presenting with neutropenia, fever, and a compatible pattern of 
abdominal pain, consider the possibility of neutropenic colitis. 
• For participants for whom the dose was increased to 1.25 mg/m2 after the first cycle 
and then experienced any toxicity requiring dose reduction, the recommended first 
dose reduction is to 1.0 mg/m2. 
• Topotecan can cause interstitial lung disease (ILD), which can be fatal. Monitor 
participants for symptoms indicative of ILD (cough, fever, dyspnea, or hypoxia), and 
discontinue topotecan if a new diagnosis of ILD is confirmed. 
 

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10.7.2. 
Recommended Dose Modifications for Irinotecan  
The starting dose for irinotecan is 100 mg/m2 or 125 mg/m2 weekly × 4, followed by 14 days off 
treatment. For participants who experience toxicity with 125 mg/m2 (described in Section 6.1.2), 
the recommended first dose reduction is to 100 mg/m2. Participants who experience toxicity at 
100 mg/m2 will undergo a first dose reduction to 75 mg/m2. Participants who experience toxicity 
at 75 mg/m2 will undergo a second dose reduction to dose level of 50 mg/m2. 
A new cycle of therapy should not begin until the granulocyte count has recovered to 
≥1500/mm3, the platelet count has recovered to ≥100,000/mm3, and treatment-related diarrhea 
has fully resolved. Treatment should be delayed for 1 to 2 weeks to allow for recovery of 
irinotecan-related toxicities. If the participant has not recovered after a 2-week delay, 
consideration should be given to discontinuing irinotecan. 
Worst Toxicity, NCI 
Gradeb 
During a Cycle of Therapya 
At Start of Next Cycle of Therapy 
(after adequate recovery), 
Compared with the Starting Dose 
of the Previous Cyclea 
Neutropenia 
 
 
1 (1500 – 1999/mm3) 
Maintain dose level 
Maintain dose level 
2 (1000 – 1499/mm3) 
↓ 25 mg/m2 
Maintain dose level 
3 (500 – 999/mm3) 
Omit dose level until resolved to ≤ grade 2, 
then  
↓ 25 mg/m2 
↓ 25 mg/m2 
4 (<500/mm3) 
Omit dose level until resolved to ≤ grade 2, 
then 
↓ 50 mg/m2 
↓ 50 mg/m2 
Neutropenic Fever 
Omit dose level until resolved, then ↓ 50 mg/m2 
↓ 50 mg/m2 
Other Hematologic 
Toxicities 
Dose modifications for leucopenia, thrombocytopenia, and anemia during a cycle of 
therapy and at the start of subsequent cycles of therapy are also based on NCI toxicity 
criteria and are the same as those recommended for neutropenia above 
Diarrhea 
 
 
1 (2 – 3 stools/day)c 
Maintain dose level 
Maintain dose level 
2 (4 – 6 stools/day)c 
↓ 25 mg/m2 
Maintain dose level 
3 (7 – 9 stools/day)c 
Omit dose level unit resolved to ≤ grade 2, then 
↓ 25 mg/m2 
↓ 25 mg/m2 
4 (≥10 stools/day)c 
Omit dose level until resolved to ≤ grade 2, 
then 
↓ 50 mg/m2 
↓ 50 mg/m2 
Other nonhematologic 
toxicitiesd 
 
 
1 
Maintain dose level 
Maintain dose level 
2 
↓ 25 mg/m2 
Maintain dose level 

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3 
Omit dose level until resolved to ≤ grade 2, 
then 
↓ 25 mg/m2 
↓ 25 mg/m2 
4 
 
Omit dose level until resolved to ≤ grade 2, 
then 
↓ 50 mg/m2 
↓ 50 mg/m2 
a. 
All dose modifications should be made based on the worst preceding toxicity. 
b. NCI- CTCAE (version 5.0). 
c. 
All numbers refer to increase over number of pre-treatment number of stools/day. 
d. Excludes anorexia, alopecia, fatigue, asthenia, and laboratory abnormalities that are not considered to be 
clinically significant. 
Source: CAMPTOSAR prescribing information, Pfizer, January 2020 
 

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10.7.3. 
Recommended Dose Modifications for Gemcitabine  
The dose reduction guidelines for gemcitabine for myelosuppression on the day of 
treatment are presented below. 
Treatment 
Day 
Absolute Neutrophil Count (× 
106/L) 
 
Platelet Count (× 106/L) 
% of Full Dose 
Day 1 
≥1500 
And 
≥100,000 
100% 
 
<1500 
Or 
<100,000 
Hold 
Day 8 
≥1500 
And 
≥100,000 
100% 
 
1000 to 1499 
Or 
75,000 to 99,999 
50% 
 
<1000 
Or 
<75,000 
Hold 
The dose reduction guidelines for gemcitabine for myelosuppression in the preceding cycle 
are presented below. 
Occurrence 
Myelosuppression During Treatment Cycle 
Dose Modification 
Initial 
occurrence 
ANC <500 × 106/L for more than 5 days  
ANC <100 × 106/L for more than 3 days Febrile 
neutropenia 
Platelets <25000 × 106/L 
Cycle delay >1 week due to toxicity 
Permanently reduce gemcitabine to 
800 mg/m2 on Days 1 and 8 
Subsequent 
occurrence 
If any of the above toxicities occurred after the initial 
dose reduction 
Permanently reduce gemcitabine to 
800 mg/m2 on Day 1 only 
Permanently discontinue gemcitabine for any of the following: 
• Unexplained dyspnea or other evidence of severe pulmonary toxicity 
• Severe hepatic toxicity 
• Hemolytic-uremic syndrome 
• Capillary leak syndrome 
• Posterior reversible encephalopathy syndrome 
Withhold gemcitabine or reduce the dose by 50% for other severe (grade 3 or 4) nonhematologic 
toxicity until resolved. No dose modifications are recommended for alopecia, nausea, or 
vomiting. 
Source: GEMZAR prescribing information, Eli Lilly and Company, May 2019 
 

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10.7.4. 
Recommended Dose Modifications for Vinorelbine  
Hematologic Toxicity 
Neutrophils on Day of Treatment 
(cells/mm3) 
Percentage of Starting Dose of Vinorelbine 
≥1500 
100% 
1000 to 1499 
50% 
<1000 
Do not administer vinorelbine. Repeat neutrophil count in 
1 week. If 3 consecutive weekly doses are held because 
neutrophil count is <1000/mm3, discontinue vinorelbine 
NOTE: For participants who experience fever and/or sepsis while neutrophil count is <1500 or participants who 
had 2 consecutive weekly doses held due to neutropenia, subsequent doses of vinorelbine should be: 
≥1500 
75% 
1000 to 1499 
37.5% 
<1000 
Do not administer vinorelbine. Repeat neutrophil count in 
1 week. 
Hepatic Impairment/Toxicity 
Serum Total Bilirubin Concentration (mg/mL) 
Percentage of Starting Dose of Vinorelbine 
≤2.0 
100% 
2.1 to 3.0 
50% 
>3.0 
25% 
Source: NAVELBINE prescribing information, GlaxoSmithKline, 2002 
 
Concurrent hematologic toxicity with hepatic impairment 
In participants with both hematologic toxicity and hepatic impairment, administer the lower of 
the doses based on the corresponding starting dose of vinorelbine determined from the respective 
schemas above. 
Neurologic toxicity 
Discontinue vinorelbine for NCI-CTCAE grade 2 or higher peripheral neuropathy or autonomic 
neuropathy causing constipation. 
 

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10.7.5. 
Recommended Dose Modifications for Single Agent Pemetrexed  
Hematological Toxicities 
Pemetrexed dose (mg/m2) 
Nadir ANC < 500/mm3 and nadir platelets ≥ 50,000/mm3 
75% of previous dose 
Nadir platelets < 50,000/mm3 without bleeding regardless of nadir 
ANC 
75% of previous dose 
Nadir platelets < 50,000/mm3 with bleedinga, regardless of nadir 
ANC 
50% of previous dose 
Non-hematological Toxicities 
Pemetrexed dose (mg/m2) 
Any grade 3 or 4 toxicities except mucositis 
75% of previous dose 
Any diarrhea requiring hospitalization (irrespective of grade) or 
grade 3 or 4 diarrhea 
75% of previous dose 
Grade 3 or 4 mucositis 
50% of previous dose 
a. 
These criteria meet the CTC version 2.0 (NCI 1998) definition of ≥ CTC grade 2 bleeding. 
Source: ALIMTA prescribing information, Eli Lilly and Company, Sep 2008 
 
 

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10.8. 
APPENDIX 8: Investigator Signature Page  
 
Investigator Statement and Signature 
I have read the attached protocol entitled “A Randomized, Open-Label, Phase 3 Trial of 
Tisotumab Vedotin vs Investigator’s Choice Chemotherapy in Second- or Third-Line Recurrent 
or Metastatic Cervical Cancer”. 
I understand and agree to the provisions of the protocol, and I accept the responsibilities listed 
above in my role as principal investigator for the study. 
 
 
_____________________________________________________  
__________________ 
Investigator Signature  
 
 
 
 
 
 
 
 
 
 
 
 
 
Date 
 
_____________________________________________________ 
Investigator Name, Printed 
 
 

Protocol 
 
SGNTV-003 
 
Study SGNTV-003  
Clinical Protocol Amendment 4 
22-Jan-2024 
Tisotumab vedotin 
Seagen Inc. – Confidential 
Page 110 of 115 
10.9. 
APPENDIX 9: Abbreviations  
1L 
first-line 
2L 
second-line 
3L 
third-line 
ADA 
anti-drug antibody 
ADC 
antibody-drug conjugate 
aPTT 
activated partial thromboplastin time 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
CI 
confidence interval 
CNS 
central nervous system 
CR 
complete response 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CXR 
chest X-ray 
DILI 
drug-induced liver injury 
DOR 
duration of response 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
EORTC 
European Organization for Research and Treatment of Cancer 
ESMO 
European Society for Medical Oncology 
EQ-5D 
standardized instrument developed as a measure of HRQOL 
FA 
final analysis 
FDA 
US Food and Drug Administration 
FFPE 
formalin-fixed paraffin-embedded 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
G-CSF 
granulocyte colony-stimulating factor 
GFR 
glomerular filtration rate 
GOG 
Gynecologic Oncology Group 
GSP 
group sequential procedure 
HBsAg 
hepatitis B surface antigen 

Protocol 
 
SGNTV-003 
 
Study SGNTV-003  
Clinical Protocol Amendment 4 
22-Jan-2024 
Tisotumab vedotin 
Seagen Inc. – Confidential 
Page 111 of 115 
HCVAb 
hepatitis C antibody 
HIV 
human immunodeficiency virus 
HR 
hazard ratio 
HRQOL 
health-related quality of life 
IA 
interim analysis 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IDMC 
independent data monitoring committee 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IHC 
immunohistochemistry 
ILD 
interstitial lung disease 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IRC 
independent review committee 
IRR  
infusion-related reaction 
ITT 
intent to treat 
IV 
intravenous 
KM 
Kaplan-Meier 
MDRD 
Modification of Diet in Renal Disease 
MMAE 
monomethyl auristatin E 
MRI 
magnetic resonance imaging 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NR 
not reported 
ORR 
objective response rate 
OS 
overall survival 
PD-1 
programmed cell death protein 1 
PD-L1 
programmed cell death ligand 1 
PET 
positron-emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic 
PR 
partial response 
PT 
prothrombin time 
Q3W 
every 3 weeks 
QLQ-C30 
Quality of Life of Cancer Patients questionnaire 
QLQ-CX24 
Quality-of-Life questionnaire cervical cancer module 

Protocol 
 
SGNTV-003 
 
Study SGNTV-003  
Clinical Protocol Amendment 4 
22-Jan-2024 
Tisotumab vedotin 
Seagen Inc. – Confidential 
Page 112 of 115 
RECIST 
Response Evaluation Criteria In Solid Tumors 
r/mCC 
recurrent/metastatic cervical cancer 
RNA 
ribonucleic acid 
RTFM 
randomization and trial supply management 
SAE 
serious adverse event 
SoA 
schedule of activities 
SUSAR 
serious unexpected suspected adverse reactions 
TEAE 
treatment-emergent adverse event 
TF 
tissue factor 
TTR 
time-to-response 
TV 
tisotumab vedotin 
ULN 
upper limit of normal 
VAS 
visual analog scale 
“Study treatment” is used to refer to either tisotumab vedotin or any of the chemotherapy options. 

Protocol 
 
SGNTV-003 
 
Study SGNTV-003  
Clinical Protocol Amendment 4 
22-Jan-2024 
Tisotumab vedotin 
Seagen Inc. – Confidential 
Page 113 of 115 
11. 
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