DREAMM 7: A Multicenter, Open-Label, Randomized Phase III Study to Evaluate the Efficacy and Safety of the Combination of Belantamab Mafodotin, Bortezomib, and Dexamethasone (B-Vd) Compared With the Combination of Daratumumab, Bortezomib and Dexamethasone (D-Vd) in Participants With Relapsed/Refractory Multiple Myeloma
Phase: PHASE3
Conditions: Multiple Myeloma
Sponsor: GlaxoSmithKline

 
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Protocol Amendment 7 Final 
 
23 Oct 2024 
1 
TITLE PAGE 
Protocol Title: DREAMM 7: A Multicenter, Open-Label, Randomized Phase III Study 
to Evaluate the Efficacy and Safety of the Combination of Belantamab Mafodotin, 
Bortezomib, and Dexamethasone (B-Vd) Compared with the Combination of 
Daratumumab, Bortezomib and Dexamethasone (D-Vd) in Participants with 
Relapsed/Refractory Multiple Myeloma 
Protocol Number: 207503 / Amendment 7 
Compound Number: GSK2857916 
Brief Title: Phase III study of belantamab mafodotin, bortezomib, and dexamethasone 
(B-Vd) versus daratumumab, bortezomib, and dexamethasone (D-Vd) in participants 
with relapsed/refractory multiple myeloma 
Study Phase: Phase 3 
Acronym: DREAMM 7 
Sponsor Name and Legal Registered Address: 
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Regulatory Agency Identifying Number(s): 
Registry 
ID 
IND number 
119333 
EU CT number 
2023-510537-28-00 
Medical Monitor Name and Contact Information can be found in the Study Reference 
Manual 
Sponsor Signatory: 
Sumita Roy-Ghanta, MD 
Clinical Development Lead 
Approval Date: 23 Oct 2024 
©2024 GSK group of companies or its licensor. All rights reserved. Unauthorized 
copying or use of this information is prohibited. 

 
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Protocol Amendment 7 JPN-1 
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Protocol Amendment 7 Investigator Agreement 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of and will comply with GCP and all applicable regulatory 
requirements. 
• 
That I will comply with the terms of the clinical study site agreement. 
• 
To ensure that all persons assisting me with the study are adequately informed 
about the GSK study intervention and other study-related duties and functions 
as described in the protocol. 
• 
To cooperate with representative(s) of GSK in the monitoring and data 
management processes of the study with respect to data entry and resolution of 
queries about the data. 

 
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Protocol Amendment 7 JPN-1 
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Study identifier 
207503 
EU CT number 
2023-510537-28-00 
Approval date 
23 Oct 2024 
Title 
DREAMM 7: A Multicenter, Open-Label, 
Randomized Phase III Study to Evaluate the Efficacy 
and Safety of the Combination of Belantamab 
Mafodotin, Bortezomib, and Dexamethasone (B-Vd) 
Compared with the Combination of Daratumumab, 
Bortezomib and Dexamethasone (D-Vd) in 
Participants with Relapsed/Refractory Multiple 
Myeloma 
Investigator name 
 
 
 
Signature 
 
 
 
Date of signature 
(DD Month YYYY) 
 

 
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Protocol Amendment 7 JPN-1 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Document Number 
Amendment 7 JPN-1 
23 Oct 2024 
TMF-20084894 
Amendment 7 
26 Sep 2024 
TMF-19845186 
Amendment 6 JPN-1 
03 Oct 2023 
TMF-17032336 
Amendment 6 
20 Sep 2023 
TMF-16739525 
Amendment 5 JPN-1 
23 Feb 2023 
TMF-15236461 
Amendment 5 
19 Dec 2022 
TMF-15039862 
Amendment 4 JPN-1 
01 Sep 2022 
TMF-14870760 
Amendment 4 
15 Jul 2022 
TMF-14626992 
Amendment 3 JPN-1 
29 Sep 2021 
TMF-14000145 
Amendment 3 
15 Jul 2021 
TMF-13879371 
Amendment 2 JPN-1 
27 Apr 2021 
TMF-12032560 
Amendment 2 
16 Dec 2020 
TMF-7925758 
Amendment 1 
16 Jul 2020 
2018N372572_01 
Original Protocol 
13 Dec 2019 
2018N372572_00 
 
Amendment 7: 23 Oct 2024 
Where this Protocol Amendment applies: 
Protocol Amendment 7 JPN-1 applies to all participants and all sites in Japan. 
Overall Rationale for the current amendment:  
This protocol has been amended to include a table of defintions of product designations 
for study treatments that  will be administered during the trial. In addition, the relevant 
product designations have been added for each study treatment agent within the Study 
Interventions Administered table (Table 7). 
Additional administrative changes have also been made to incorporate program level 
changes related to EU CTR disclosure requirements. 
List of main changes in the protocol and their rationale: 
Section # and title 
Description of change 
Brief rationale 
Section 1.3 Schedule of 
Activities  
Table 1 and Table 2 Schedule of 
Activities (SoA) have been updated. The 
text regarding Survival follow-up: has 
been updated to include “Subsequent 
visits should be 12 weeks (14-day 
window) from the date of contact of the 
prior survival follow-up visit.” 
Clarification of the frequency and 
timing of Survival follow-up visits. 
Section 6.1 Study 
Intervention(s) Administered 
Table 7 has been updated to include 
additional details/definitions for each 
study treatment. 
Alignment with program-level 
updates to identify the product 
designations for each of the study 
treatments within the protocol. 

 
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Section # and title 
Description of change 
Brief rationale 
Section 7.1.2 Liver Chemistry 
Stopping Criteria 
Figure 4 and Figure 5 have been updated 
to the current protocol template which 
updates the criteria of total bilirubin 
≥2xULN (>35% direct bilirubin) to be total 
bilirubin ≥2xULN. 
Alignment with the requirements in 
the Sponsor’s standard protocol 
template. 
Section 8 Study Assessments 
and Procedures 
Collection of sex, race and ethnicity data 
are necessary to assess and monitor the 
diversity of the study participants, and to 
determine if the study participants are 
truly representative of the impacted 
population. 
Rationale for the collection of sex, 
race and ethnicity data. 
Section 10.1.10 Study and Site 
Closure 
The text has been updated to specify 
reasons for study termination and for site 
termination. 
Alignment with program-level 
updates to clarify the 
circumstances for closures specific 
to study level termination and site 
level termination. 
Section 10.1.11 Third parties 
and Sub-Contractors 
This appendix has been removed and is 
now contained in a separate document. 
Alignment with the Sponsor’s 
standard protocol template and 
ways of working; a separate 
document has been created. 
Section 10.4 Appendix 4: Liver 
Safety: Required Actions, 
Follow-up Assessments, and 
Study Treatment Rechallenge 
Guidelines 
The text in the table for the row: 
Bilirubin1, 2 ALT  3xULN and total 
bilirubin  2xULN (>35% direct bilirubin) 
has been updated to: 
Bilirubin1, 2 ALT  3xULN and total 
bilirubin  2xULN 
Alignment with the requirements in 
the Sponsor’s standard protocol 
template. 
Section 10.14 Appendix 14: 
Abbreviations and Trademarks 
Addition of a definitions table and 
updated the section name to Section 
10.14 Appendix 14: Abbreviations, 
Definitions and Trademarks 
Alignment with program-level 
updates to provide definitions for 
product designations of study 
treatments within the protocol. 

 
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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 4 
List of main changes in the protocol and their rationale: ........................................... 4 
1. 
PROTOCOL SUMMARY ........................................................................................ 13 
1.1. 
Synopsis ..................................................................................................... 13 
1.2. 
Schema ...................................................................................................... 17 
1.3. 
Schedule of Activities (SoA) ........................................................................ 18 
2. 
INTRODUCTION .................................................................................................... 38 
2.1. 
Study Rationale .......................................................................................... 38 
2.2. 
Background ................................................................................................ 39 
2.2.1. 
Current Treatment of Multiple Myeloma ....................................... 39 
2.2.2. 
Role of B-Cell Maturation Antigen in Multiple Myeloma. ............... 40 
2.2.3. 
Antibody-Drug Conjugate Belantamab Mafodotin ........................ 40 
2.2.4. 
Clinical Experience with Belantamab Mafodotin ........................... 41 
2.3. 
Benefit/Risk Assessment ............................................................................ 45 
2.3.1. 
Summary of Risk Assessment for Belantamab Mafodotin 
(Treatment Arm A), Daratumumab (Treatment Arm B), 
and Bor/Dex (Treatment Arms A and B) ...................................... 45 
2.3.2. 
Benefit Assessment ..................................................................... 52 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 53 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 54 
4. 
STUDY DESIGN .................................................................................................... 57 
4.1. 
Overall Design ............................................................................................ 57 
4.2. 
Scientific Rationale for Study Design .......................................................... 58 
4.3. 
Justification for Dose .................................................................................. 59 
4.3.1. 
Belantamab Mafodotin Dose ........................................................ 59 
4.3.2. 
Daratumumab Dose ..................................................................... 60 
4.3.3. 
Bortezomib Dose ......................................................................... 60 
4.3.4. 
Dexamethasone Dose ................................................................. 61 
4.4. 
End of Study Definition ............................................................................... 61 
5. 
STUDY POPULATION ........................................................................................... 62 
5.1. 
Inclusion Criteria ......................................................................................... 62 
5.2. 
Exclusion Criteria ........................................................................................ 64 
5.3. 
Lifestyle Considerations .............................................................................. 66 
5.4. 
Screen Failures........................................................................................... 67 
6. 
STUDY INTERVENTION ........................................................................................ 68 
6.1. 
Study Intervention(s) Administered ............................................................. 68 
6.1.1. 
Treatment Arm A Dosing Schedule .............................................. 69 
6.1.2. 
Treatment Arm B Dosing Schedule .............................................. 69 
6.1.3. 
Belantamab Mafodotin ................................................................. 71 
6.1.4. 
Daratumumab .............................................................................. 73 
6.1.5. 
Bortezomib .................................................................................. 74 
6.1.6. 
Dexamethasone........................................................................... 75 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 75 

 
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6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 76 
6.4. 
Study Intervention Compliance ................................................................... 76 
6.5. 
Concomitant Therapy.................................................................................. 77 
6.5.1. 
Permitted Concomitant Therapies ................................................ 77 
6.5.2. 
Prohibited Concomitant Therapies ............................................... 77 
6.6. 
Dose Modification and Delay ...................................................................... 79 
6.6.1. 
Belantamab Mafodotin ................................................................. 79 
6.6.2. 
Daratumumab .............................................................................. 84 
6.6.3. 
Bortezomib .................................................................................. 84 
6.6.4. 
Dexamethasone........................................................................... 87 
6.6.5. 
Guidance on Dose Delays for Treatment Arm A and B ................ 87 
6.6.6. 
Management of Hepatitis B+ participants ..................................... 89 
6.7. 
Intervention After the End of the Study ....................................................... 90 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 91 
7.1. 
Discontinuation of Study Intervention .......................................................... 91 
7.1.1. 
Discontinuation of Individual Components of Combination 
Study Treatment .......................................................................... 92 
7.1.2. 
Liver Chemistry Stopping Criteria ................................................ 93 
7.1.3. 
Corneal Event Stopping Criteria ................................................... 95 
7.1.4. 
Infusion-Related Reactions Stopping Criteria ............................... 95 
7.1.5. 
Allergic Reactions and Anaphylactic Reactions Stopping 
Criteria ......................................................................................... 96 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 96 
7.3. 
Lost to Follow Up ........................................................................................ 96 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 98 
8.1. 
Efficacy Assessments ............................................................................... 100 
8.1.1. 
Response Evaluation ................................................................. 101 
8.1.2. 
Assessment of CR Where Daratumumab Interference is 
Suspected .................................................................................. 101 
8.1.3. 
MRD Assessment and PET-CT Imaging .................................... 102 
8.2. 
Safety Assessments ................................................................................. 102 
8.2.1. 
Physical Examinations ............................................................... 103 
8.2.2. 
ECOG Performance Status ........................................................ 103 
8.2.3. 
Vital Signs .................................................................................. 103 
8.2.4. 
Electrocardiogram ...................................................................... 104 
8.2.5. 
Clinical Safety Laboratory Assessments .................................... 104 
8.2.6. 
Ophthalmic Assessments .......................................................... 105 
8.2.7. 
Patient-Reported Outcome Version of the Common Term 
Criteria for Adverse Events (PRO-CTCAE) ................................ 106 
8.2.8. 
Pregnancy Testing (WOCBP Only) ............................................ 107 
8.3. 
Adverse Events and Serious Adverse Events ........................................... 107 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................. 107 
8.3.2. 
Method of Detecting AEs and SAEs ........................................... 108 
8.3.3. 
Follow-up of AEs and SAEs ....................................................... 108 
8.3.4. 
Regulatory Reporting Requirements for SAEs ........................... 108 
8.3.5. 
Pregnancy ................................................................................. 109 
8.3.6. 
Cardiovascular and Death Events .............................................. 109 
8.3.7. 
Adverse Events of Special Interest ............................................ 109 

 
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8.4. 
Treatment of Overdose ............................................................................. 110 
8.5. 
Pharmacokinetics ..................................................................................... 110 
8.5.1. 
Belantamab Mafodotin Blood Sample Collection for 
Pharmacokinetics ...................................................................... 110 
8.5.2. 
Belantamab Mafodotin PK Sample Analysis .............................. 112 
8.5.3. 
Daratumumab and Bortezomib .................................................. 112 
8.6. 
Belantamab Mafodotin Immunogenicity .................................................... 112 
8.7. 
Pharmacodynamics .................................................................................. 113 
8.8. 
Genetics ................................................................................................... 113 
8.9. 
Biomarkers ............................................................................................... 114 
8.9.1. 
Soluble BCMA ........................................................................... 114 
8.9.2. 
Tumor-related Biomarkers ......................................................... 116 
8.9.3. 
Circulating Cell-Free DNA (cfDNA) Analysis .............................. 117 
8.10. 
Health-Related Quality of Life ................................................................... 117 
8.10.1. 
European Organization for Research and Treatment of 
Cancer Quality of Life Questionnaire 30-item Core module 
(EORTC QLQ-C30) ................................................................... 118 
8.10.2. 
European Organization for Research and Treatment of 
Cancer Item Library 52 (disease symptoms domain from 
the EORTC Quality of Life Questionnaire 20-item Multiple 
Myeloma module (EORTC QLQ-MY20) ..................................... 118 
8.10.3. 
EuroQol Questionnaire (EQ-5D-3L) ........................................... 118 
8.10.4. 
Functional Assessment of Cancer Therapy – General 
Population (FACT-GP5) ............................................................. 119 
8.10.5. 
Patient Global Impression Items ................................................ 119 
8.11. 
Visual Function Questionnaires ................................................................ 119 
8.12. 
Non-protocol Specified Health Care Resource Utilization ......................... 119 
9. 
STATISTICAL CONSIDERATIONS ...................................................................... 120 
9.1. 
Statistical Hypotheses............................................................................... 120 
9.2. 
Multiple Comparisons and Multiplicity ....................................................... 121 
9.3. 
Sample Size Determination ...................................................................... 121 
9.4. 
Populations for Analyses .......................................................................... 123 
9.5. 
Statistical Analyses ................................................................................... 123 
9.5.1. 
Efficacy Analyses ....................................................................... 123 
9.5.2. 
Safety Analyses ......................................................................... 127 
9.5.3. 
Pharmacokinetic Analyses ......................................................... 127 
9.5.4. 
Pharmacokinetic/PD Analyses ................................................... 128 
9.5.5. 
Other Analyses .......................................................................... 128 
9.6. 
Planned Analyses ..................................................................................... 128 
9.6.1. 
Periodic IDMC Safety Reviews and CPMS Early Access ........... 128 
9.6.2. 
Interim Analyses ........................................................................ 128 
9.6.3. 
Final Analysis ............................................................................ 130 
9.6.4. 
Sequence of Interim and Other Planned Analyses ..................... 130 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................. 132 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations .......................................................................................... 132 
10.1.1. 
Regulatory and Ethical Considerations ...................................... 132 
10.1.2. 
Financial Disclosure ................................................................... 132 
10.1.3. 
Informed Consent Process ........................................................ 133 

 
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10.1.4. 
Data Protection .......................................................................... 133 
10.1.5. 
Committees Structure ................................................................ 134 
10.1.6. 
Publication Policy ....................................................................... 134 
10.1.7. 
Dissemination of Clinical Study Data ......................................... 134 
10.1.8. 
Data Quality Assurance ............................................................. 135 
10.1.9. 
Source Documents .................................................................... 136 
10.1.10. Study and Site Closure .............................................................. 136 
10.2. 
Appendix 2: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ..................................... 138 
10.2.1. 
Definition of AE .......................................................................... 138 
10.2.2. 
Definition of SAE ........................................................................ 139 
10.2.3. 
Definition of Cardiovascular Events ........................................... 141 
10.2.4. 
Recording and Follow-Up of AE and SAE .................................. 141 
10.2.5. 
Reporting of SAEs to GSK ......................................................... 143 
10.3. 
Appendix 3: Contraceptive Guidance and Collection of Pregnancy 
Information ................................................................................................ 144 
10.3.1. 
Definitions .................................................................................. 144 
10.3.2. 
Contraception Guidance ............................................................ 145 
10.3.3. 
Collection of Pregnancy Information .......................................... 146 
10.4. 
Appendix 4: Liver Safety: Required Actions, Follow-up 
Assessments, and Study Treatment Rechallenge Guidelines ................... 148 
10.4.1. 
Liver Safety Drug Restart or Re-Challenge Guidelines .............. 150 
10.5. 
Appendix 5: Genetics ................................................................................ 153 
10.6. 
Appendix 6: Eastern Cooperative Oncology Group (ECOG) 
Functional Status ...................................................................................... 154 
10.7. 
Appendix 7: Modified Diet in Renal Disease (MDRD) Formula .................. 155 
10.8. 
Appendix 8: New York Heart Association Classification ............................ 156 
10.9. 
Appendix 9: Corneal Event Grading and Prophylactic Interventions 
for Corneal Toxicity (Treatment Arm A) ..................................................... 157 
10.10. Appendix 10: Eye Care Specialist’s Qualifications and 
Requirements ........................................................................................... 159 
10.11. Appendix 11: Progression-Free Survival Event and Censoring Rules ....... 160 
10.12. Appendix 12: Country Specific Requirements ........................................... 162 
10.13. Appendix 13: Revised International Staging System for Multiple 
Myeloma ................................................................................................... 163 
10.14. Appendix 14: Abbreviations, Definitions and Trademarks ......................... 164 
10.15. Appendix 15: Home Healthcare and Telemedicine Approaches ................ 171 
10.16. Appendix 16: Data Management/Monitoring ............................................. 174 
10.17. Appendix 17: Protocol Amendment History ............................................... 175 
10.18. Appendix 18 COUNTRY SPECIFIC REQUIREMENTS (JAPAN) .............. 197 
10.18.1. Study Conduct Considerations ................................................... 197 
10.18.2. Unapproved Medical Device ...................................................... 198 
10.18.3. Modification to the full protocol ................................................... 205 
11. REFERENCES ..................................................................................................... 208 
 

 
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LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities – Treatment Arm A (Belantamab 
Mafodotin/Bortezomib/Dexamethasone) ................................................ 18 
Table 2 
Schedule of Activities - Treatment Arm B 
(Daratumumab/Bortezomib/Dexamethasone) ........................................ 27 
Table 3 
Bone Marrow Aspirate/Biopsy Collection (Treatment Arm A and 
Treatment Arm B) ................................................................................... 35 
Table 4 
Hepatitis B (HBV) SoA – Additional Procedures ..................................... 36 
Table 5 
Hepatitis C (HCV) SoA – Additional Procedures..................................... 37 
Table 6 
Adequate Organ System Function Based on Safety 
Assessments .......................................................................................... 63 
Table 7 
Study Treatment..................................................................................... 68 
Table 8 
Administration of Belantamab Mafodotin ................................................ 71 
Table 9 
Dose Levels Belantamab Mafodotin: Treatment Arm A .......................... 80 
Table 10 
Dose Modification Guidelines for Adverse Events Associated 
with Belantamab Mafodotin .................................................................... 81 
Table 11 
Dose Modification Guidelines for Belantamab Mafodotin 
Treatment-Related Corneal Events based on KVA1 Scale ...................... 83 
Table 12 
General Dose Modification and Management Guidelines for 
Drug-Related Adverse Events Not Otherwise Specified ......................... 83 
Table 13 
Dose Levels for Bortezomib ................................................................... 85 
Table 14 
Dose Modification Guidelines for Hematologic and Other 
Toxicities Associated with Bortezomib and Dexamethasone 
Treatment............................................................................................... 86 
Table 15 
Permitted Dose Reductions for Dexamethasone in Both Arms ............... 87 
Table 16 
Dose Delays for Treatment Arm A (Cycles 1-8 only) .............................. 88 
Table 17 
Dose Delays for Treatment Arm B (Cycles 1-8) ...................................... 88 
Table 18 
Dose Modification Guideline for Hepatitis B Reactivation ....................... 90 
Table 19 
List of Clinical Laboratory Tests ............................................................. 99 
Table 20 
PK Schedule for Enhanced PK Collection (Treatment Arm A 
Only) .................................................................................................... 111 

 
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Table 21 
PK Schedule for Standard PK Collection (Treatment Arm A Only) ....... 112 
Table 22 
Treatment Arm A sBCMA Blood Collection (Enhanced PK 
Cohort) ................................................................................................. 115 
Table 23 
Treatment Arm A sBCMA Blood Collection (Standard PK Cohort) ....... 116 
Table 24 
Treatment Arm B sBCMA Blood Collection .......................................... 116 
Table 25 
Statistical Analytical Methods: Efficacy ................................................. 124 
Table 26 
Statistical Analytical Methods: Safety ................................................... 127 
Table 27 
 Summary of Planned Interim Analyses ................................................ 129 
Table 28 
 Stopping Boundaries for PFS Interim and Primary Analyses ............... 129 
Table 29 
 Details of Planned Analyses ................................................................ 130 
Table 30 
Keratopathy Visual Acuity (KVA) Scale for Treatment-related 
Corneal Events:.................................................................................... 157 
Table 31 
Prophylactic Measures for Corneal Toxicity Associated with 
Belantamab Mafodotin ......................................................................... 158 
 

 
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LIST OF FIGURES 
PAGE 
Figure 1 
Mechanism of Action of Belantamab Mafodotin ...................................... 41 
Figure 2 
Summary of Dosing Schedule for Treatment Arm A (Belantamab 
mafodotin/bor/dex) ................................................................................. 69 
Figure 3 
Summary of Dosing Schedule for Treatment Arm B 
(Daratumumab/bor/dex) ......................................................................... 70 
Figure 4 
Liver Stopping and Monitoring Event Algorithm (ALT ≥ 3xULN) ............. 93 
Figure 5 
Liver Stopping and Monitoring Event Algorithm for ALT ≥ 3xULN 
but <8xULN ............................................................................................ 94 

 
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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: 
DREAMM 7: A Multicenter, Open-Label, Randomized Phase III Study to Evaluate the 
Efficacy and Safety of the Combination of Belantamab Mafodotin, Bortezomib, and 
Dexamethasone (B-Vd) Compared with the Combination of Daratumumab, Bortezomib 
and Dexamethasone (D-Vd) in Participants with Relapsed/Refractory Multiple Myeloma 
Short Title: 
Phase III study of belantamab mafodotin, bortezomib, and dexamethasone (B-Vd) versus 
daratumumab, bortezomib, and dexamethasone (D-Vd) in participants with 
relapsed/refractory multiple myeloma 
Rationale: 
In relapsed or refractory multiple myeloma (RRMM), combination therapies utilizing 
agents with differing modes of action have dramatically improved outcomes. Combining 
active agents with bortezomib/dexamethasone (bor/dex) treatment can yield improved 
patient outcomes with acceptable toxicity profiles, establishing new global standard of 
care (SoC) regimens. The approval of the anti-CD38 antibody daratumumab has 
demonstrated that the addition of a targeted monoclonal antibody, with activity as a 
monotherapy, to bor/dex can result in significant improvements in progression-free 
survival (PFS) in patients with RRMM, and the combination of daratumumab with 
bor/dex is currently a widely accepted SoC for MM patients who have received at least 1 
prior line of therapy.  
Belantamab mafodotin (GSK2857916) has demonstrated strong single-agent activity in 
RRMM in the First-Time-in-Human (FTIH) study BMA117159. As of 31 August 2018, 
the Overall Response Rate (ORR) in 35 participants treated at the recommended Phase 2 
dose of 3.4 mg/kg was 60.0% (95% CI: 42.1, 76.1) and the median PFS was 12.0 months 
(95% CI: 3.1, NR) in a heavily pre-treated population (57% ≥5 prior lines of therapy). In 
participants refractory to both immunomodulators and proteasome inhibitors (n=32/35), 
the ORR was 56% (95% CI: 37.7, 73.6). 
In Study BMA117159, the maximum clinical benefit (ORR) was observed at the 
3.4 mg/kg dose level, but a significant number of participants required dose delays and 
dose reductions to manage adverse events. In phase II Study 205678, belantamab 
mafodotin was further evaluated as monotherapy in RRMM patients at the dose of 
2.5 mg/kg and 3.4 mg/kg Q3W; both dose levels, 2.5 and 3.4 mg/kg, have a positive 
benefit/risk profile. Overall, there were no new safety signals identified in the 205678 
study, and the profile of adverse events was similar to the experience in DREAMM-1 for 
both arms. The dose of 2.5 mg/kg appears to have a lower incidence of adverse events 
and less frequent dose delays and reductions, and it results in similar efficacy with 
3.4 mg/kg dose as measured by ORR. The dose of 2.5 mg/kg Q3W has been further 

 
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evaluated in combination with bortezomib and dexamethasone in Study 207497 and 
based on the safety evaluation, this dose has been selected for this study.  
It is hypothesized that the combination of belantamab mafodotin and bor/dex will lead to 
greater patient benefit, as measured by progression-free survival (PFS), compared to the 
SoC combination of daratumumab and bor/dex. While there are some potential overlaps 
in the pattern of identified toxicities between belantamab mafodotin and bor/dex 
(primarily hematologic), they are expected to be manageable. 
Primary and Secondary Objectives and Endpoints: 
Objectives 
Endpoints1 
Primary 
The primary objective of this study is to 
compare the efficacy of belantamab 
mafodotin in combination with bortezomib 
and dexamethasone (bor/dex) with that of 
daratumumab in combination with bor/dex in 
participants with RRMM 
• 
Progression-Free Survival (PFS), defined as the time from the 
date of randomization until the earliest date of documented 
disease progression or death due to any cause 
Key Secondary 
To compare the efficacy of belantamab 
mafodotin in combination with bor/dex with 
that of daratumumab in combination with 
bor/dex in participants with RRMM 
• 
Overall Survival (OS), defined as the time from the date of 
randomization until the date of death due to any cause 
 
• 
Duration of Response (DoR), defined as the time from first 
documented evidence of PR or better until progressive 
disease (PD) or death due to any cause 
• 
Minimal Residual Disease (MRD) negativity rate, defined as 
the percentage of participants who are MRD negative by next-
generation sequencing (NGS) 
Secondary 
To further assess the efficacy of belantamab 
mafodotin in combination with bor/dex with 
that of daratumumab in combination with 
bor/dex in terms of other efficacy outcomes in 
participants with RRMM 
• 
Complete Response Rate (CRR), defined as the percentage 
of participants with a confirmed complete response (CR) or 
better (i.e., CR, stringent complete response (sCR)) 
• 
Overall Response Rate (ORR), defined as the percentage of 
participants with a confirmed partial response (PR) or better 
(i.e., PR, VGPR, CR, sCR) 
• 
Clinical Benefit Rate (CBR), defined as the percentage of 
participants with a confirmed minimal response (MR) or better 
per International Myeloma Working Group (IMWG) 
• 
Time to Response (TTR), defined as the time between the 
date of randomization and the first documented evidence of 
response (PR or better) among participants who achieve 
confirmed PR or better 

 
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15 
Objectives 
Endpoints1 
• 
Time to Progression (TTP), defined as the time from the date 
of randomization until the earliest date of documented PD or 
death due to PD 
• 
PFS2, defined as time from randomization to disease 
progression after initiation of new anti-myeloma therapy or 
death from any cause, whichever is earlier. If disease 
progression after new anti-myeloma therapy cannot be 
measured, a PFS event is defined as the date of 
discontinuation of new anti-myeloma therapy, or death from 
any cause, whichever is earlier. 
To evaluate the safety and tolerability of 
belantamab mafodotin when administered in 
combination with bor/dex 
• 
Incidence of adverse events (AEs) and changes in laboratory 
parameters 
• 
Ocular findings on ophthalmic exam 
To further describe the exposure to 
belantamab mafodotin when administered in 
combination with bor/dex 
• 
Plasma concentrations of belantamab mafodotin, and cys-
mcMMAF 
To assess anti-drug antibodies (ADAs) 
against belantamab mafodotin 
• 
Incidence and titers of ADAs against belantamab mafodotin 
To evaluate the safety and tolerability of 
belantamab mafodotin based on self-reported 
symptomatic adverse effects when 
administered in combination with bor/dex 
• 
Maximum post-baseline PRO-CTCAE score for each item 
attribute 
To evaluate and compare changes in 
symptoms and health-related quality of life 
(HRQOL)  
• 
Change from baseline in HRQOL as measured by EORTC 
QLQ-C30 and EORTC IL52 (disease symptoms domain from 
the EORTC QLQ-MY20) 
1. All categories of disease response (sCR, CR, VGPR, PR, SD, PD) used in the calculation of study endpoints will 
be determined by an IRC using IMWG 2016 criteria. 
 
Overall Design: 
This is a multicenter Phase III, randomized, open-label study evaluating the efficacy and 
safety of the combination of belantamab mafodotin and bor/dex versus with the 
combination of daratumumab and bor/dex in participants with RRMM. 
Disclosure Statement:  
This is a randomized, parallel group treatment study with 2 arms and no blinding.  
Number of Participants: 
Global Study: Approximately 600 participants will be screened to achieve about 478 
participants randomized in a 1:1 ratio between the 2 study arms. There will be a
% 
global enrollment cap on North East Asia Countries. In these countries, the respective 
regulatory authorities require a sufficient number of their country populations to be 
included in marketing authorizations.  
CCI

 
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16 
Japan Expansion Cohort: Once the enrollment into the global study is completed, 
recruitment into an expansion cohort will continue in Japan to enroll a total of 
Japanese participants, including any Japanese participants enrolled in the global study. 
These additional participants in the expansion cohort will not be included in the statistical 
analysis of the global study. Details will be provided in the Japan-specific Statistical 
Analysis Plan (SAP). 
Intervention Groups and Duration: 
Following screening, participants will be stratified based on the number of prior lines of 
therapy, prior treatment with bortezomib and revised international staging system (R-ISS, 
see Appendix 13) at screening, and centrally randomized in a 1:1 ratio to either arm. No 
more than
 of participants with 2 or more prior lines of treatment will be enrolled 
(including those in Japan expansion cohorts). No cross-over will be allowed. 
Treatment Arm A: Belantamab mafodotin 2.5 mg/kg (IV) Q3W to progression. Cycles 
1 through 8: bortezomib 1.3 mg/m2 (SC) on Days 1, 4, 8, and 11 of every 21-day cycle; 
and dexamethasone 20 mg (IV or PO) on the day of and the day after bortezomib 
treatment. 
Treatment Arm B: Daratumumab 16 mg/kg (IV) weekly for Cycles 1 through 3 (Weeks 
1-9; 21-day cycles, total of 9 doses), on Day 1 of Cycles 4 through 8 (Weeks 10 – 24; 21-
day cycles, total of 5 doses), and then every 4 weeks from Cycle 9 (Week 25) onwards 
until progression (28-day cycles). For Cycles 1 through 8: bortezomib 1.3 mg/m2 (SC) on 
Days 1, 4, 8, and 11 of every 21-day cycle; and dexamethasone 20 mg (IV or PO, but IV 
prior to first daratumumab dose) on the day of and the day after bortezomib treatment. 
Treatment will continue in both arms until progressive disease, death, unacceptable 
toxicity, withdrawal of consent, or end of study, whichever occurs first. Dose delays or 
reductions may be required following potential drug-associated toxicities. 
Data Monitoring/Other Committee: Yes, refer to Section 10.1.5. 
 
CCI
CCI

 
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17 
1.2. 
Schema 
 
* 
Stratification: Prior lines of treatment (1 vs 2/3 vs ≥4), R-ISS (I vs II/III), Prior bortezomib (yes vs no). 
†  
Reduce starting dose of dexamethasone to 10 mg for participants older than 75 years of age, who have a body-mass index of less than 18.5, who had previous unacceptable 
side effects associated with glucocorticoid therapy, or who are unable to tolerate the starting dose (For guidance on further dose modification, see Table 15, Section 6.6.4).  
PD = Progressive Disease; C1D1 = Cycle 1 Day 1; IV = intravenous; SC = subcutaneous; Q1W = once weekly; Q3W = once every 3 weeks; Q4W = once every 4 weeks; PFS = 
Progression-free Survival; OS = Overall Survival.  

 
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18 
1.3. 
Schedule of Activities (SoA) 
Table 1 
Schedule of Activities – Treatment Arm A (Belantamab Mafodotin/Bortezomib/Dexamethasone) 
• 
Screening assessments do not need to be repeated on C1D1 if conducted within 72 hours of C1D1 dosing, unless otherwise specified.  
• 
The 28-day Screening period is initiated upon signature of the informed consent form (Day 1). The full 28 days can be taken to determine the eligibility of the participants. 
Participants can be randomized during or upon completion of the 28 days i.e. the day after the Screening period has ended. Study treatment (C1D1) should be initiated within 
72 hours after randomization.  
• 
Precise timing of treatment cycles may vary due to treatment delays, but participants must still visit for efficacy assessments regularly regardless of when they receive 
treatment. The schedule for efficacy assessments is Q3W. These are referred to as ‘fixed visits’ or ‘weeks visits’ and should be scheduled from C1D1. 
• 
Assessments scheduled on days of dosing should be done prior to drug administration unless otherwise specified. All assessments should be carried out even if a participant is 
not dosed except for the following:  vital signs, weight, pregnancy test and PK where applicable.  
• 
End of Treatment (EOT) visit will occur within 30 days from the last cycle, or prior to initiation of new anti-myeloma therapy (whichever occurs first). AEs and SAEs will be 
collected up to at least 70 days after the last dose of belantamab mafodotin, either via phone or a follow up visit. Participants who have ocular symptoms at EOT will be 
followed up for ocular exams and OSDI questionnaire as described in Section 8.2.6. After discontinuation of study treatment, the participant should continue disease 
assessments as per the SoA.  Every effort should be made to confirm disease progression per the IMWG criteria prior to initiating a new anti-myeloma therapy. 
• 
PFS follow-up: Participants who permanently discontinue study treatment for reasons other than disease progression will remain in the study and will be followed for PFS 
according to the protocol schedule until: 
o 
Disease progression according to IMWG criteria (then move to Survival follow-up) 
o 
New anti-myeloma therapy is initiated (then move to Survival follow-up) 
o 
Death 
o 
Withdrawal of consent 
o 
Loss to follow-up 
o 
End of study 
• 
Survival follow-up: Participants will be followed for survival and subsequent anti-myeloma therapy (PFS2) by chart review, phone call, or any form of communication every 12 
weeks (14-day window) from the last Q3W assessment visit until death, withdrawal of consent, lost to follow-up or end of the study, whichever comes first. Subsequent visits 
should be 12 weeks (14-day window) beginning from the date of contact of the prior survival follow-up visit. Participant does not need to come in for visit unless they are being 
followed for treatment-related changes in vision that are present at the EoT. Record the participant’s survival status and whether subsequent treatment for disease was given. 
• 
GSK may request that updated survival data be collected on all treated/randomized participants outside the protocol window noted in the Schedule of Assessments. At the time 
of the request, the site will determine survival status for each participant by the method agreed with the participant, unless the participant has withdrawn consent for survival 
follow-up. Where permitted, data from publicly available death registers will be used for participants withdrawn from study or lost to follow-up prior to death. 
• 
For details on Home Healthcare and Telemedicine Approaches, please refer to Appendix 15. 
 

 
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19 
Schedule of Activities – Treatment Arm A (Belantamab Mafodotin/Bortezomib/Dexamethasone) 
Procedure 
Screening 
(-28days) 
Treatment Period (±3 days) 
End of Treatment 
(EOT) 
Follow up 
Cycle /  
Visit 
C1 
C2-8 
C1-8  
C1-8  
C1-8  
C9 + 
Fixed Visits 
Q3W 
(Starting at 
Week 4) 
 
PFS 
Follow-
up 
Visit 
Q3W 
(±3 
days) 
OS 
Follow-
up Visit 
Q12W 
(±14 
days) 
Day 
 
D1 
D4 
D8 
D11 
D1 
 
 
 
 
Informed Consent1,2 
X 
 
 
 
 
 
 
 
 
 
 
Baseline Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical/Disease History, and 
Characteristics 
X 
 
 
 
 
 
 
 
 
 
 
Body Weight 
X 
X 
X 
 
 
 
X 
 
X 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
Safety 
Physical Exam3 
X 
X 
X 
 
 
 
X 
 
X 
X 
 
ECOG Performance Status 
X 
 
X 
 
 
 
X 
 
X 
X 
 
Ocular Exam4 
X 
 
X4 (see 
footnote) 
 
 
 
X4 (see footnote) 
X4 (see 
footnote) 
X 
X4 
X4 
Vital Signs5 
(BP, Heart rate, Body Temp) 
X 
X 
X 
If clinically indicated 
X 
 
X 
 
 
12-Lead ECG6 
X 
 
 
 
 
 
 
 
 
Adverse Events/SAEs 
 
Adverse events and SAEs will be collected throughout the study until at least 70 days after the last dose of belantamab 
mafodotin. SAEs related to study participation or related to belantamab mafodotin are collected from time of consent until end of 
study. See Section 8.3.1. 
Concomitant Medications  
Concomitant medications will be collected, as reported by the participant or through participant medical record review. 
Survival Follow-up Phone call7 
 
 
 
 
 
 
 
 
 
 
X 
Laboratory Assessments8 
Hematology9,10 
X 
X 
X 
X 
X 
X 
X 
X1 
X 
X 
 
Clinical Chemistry9, 10 
X 
X 
X 
X 
X 
X 
X 
X1 
X 
X 
 
HbA1c 
As clinically indicated 
 
eGFR11 
X 
X 
 
 
 
 
 
X1 
X 
 
 

 
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Protocol Amendment 7 JPN-1 
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20 
Schedule of Activities – Treatment Arm A (Belantamab Mafodotin/Bortezomib/Dexamethasone) 
Procedure 
Screening 
(-28days) 
Treatment Period (±3 days) 
End of Treatment 
(EOT) 
Follow up 
Cycle /  
Visit 
C1 
C2-8 
C1-8  
C1-8  
C1-8  
C9 + 
Fixed Visits 
Q3W 
(Starting at 
Week 4) 
 
PFS 
Follow-
up 
Visit 
Q3W 
(±3 
days) 
OS 
Follow-
up Visit 
Q12W 
(±14 
days) 
Day 
 
D1 
D4 
D8 
D11 
D1 
 
 
 
 
Urine dipstick for protein OR Spot 
Urine (Albumin/Creatinine ratio12) 
X 
X 
 
 
 
 
 
X1 
X 
 
 
HbsAg, HbcAb, Hep C Ab, Hep C 
RNA13 
X 
 
 
 
 
 
 
 
 
 
 
Indirect antiglobulin test (Indirect 
Coombs test) 
X 
 
Blood type and screen 
X 
 
Pregnancy Test for WOCBP14 
X 
X 
X 
 
 
 
X 
 
X 
X13 
X13 
(phone 
call only) 
Disease Evaluations:  Baseline disease assessments completed within 28 days (30 days for imaging) of C1D1 do not need to be repeated on C1D1. For participants who are 
discontinuing IP due to PD, confirmation based on laboratory parameters must be performed from a different sample collection (serum/urine) before institution of any new anti-
myeloma therapy and preferably within 14 days of the date of the initial assessment showing unconfirmed disease progression. This may be performed at the EOT visit.  
β2 Microglobulin 
X 
 
 
 
 
 
 
 
 
 
 
SPEP (Serum Protein 
Electrophoresis) 
X 
 
 
 
 
 
 
X1 
X 
X 
 
UPEP (Urine Protein 
Electrophoresis) (on 24-hour 
collected urine)  
X 
 
 
 
 
 
 
X1 
X 
X 
 
Serum M Protein Calculation 
X 
 
 
 
 
 
 
X1 
X 
X 
 
Serum Kappa Lambda Free LC, 
FLC Ratio 
X 
 
 
 
 
 
 
X1 
X 
X 
 
Serum Immunofixation 
X 
 
Serum immunofixation must be performed each time that M-protein is not quantifiable by SPEP 
(0g/dL) 
 
Urine Immunofixation 
X 
 

 
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Protocol Amendment 7 JPN-1 
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21 
Schedule of Activities – Treatment Arm A (Belantamab Mafodotin/Bortezomib/Dexamethasone) 
Procedure 
Screening 
(-28days) 
Treatment Period (±3 days) 
End of Treatment 
(EOT) 
Follow up 
Cycle /  
Visit 
C1 
C2-8 
C1-8  
C1-8  
C1-8  
C9 + 
Fixed Visits 
Q3W 
(Starting at 
Week 4) 
 
PFS 
Follow-
up 
Visit 
Q3W 
(±3 
days) 
OS 
Follow-
up Visit 
Q12W 
(±14 
days) 
Day 
 
D1 
D4 
D8 
D11 
D1 
 
 
 
 
Urine immunofixation must be performed each time that M-protein is not quantifiable by UPEP 
(0 mg/24 hr) AND SPEP (0 g/dL) 
Calcium Corrected for Albumin 
(serum) 
X 
 
 
 
 
 
 
X1 
X 
X 
 
lgG, lgM, lgA 
X 
 
 
 
 
 
 
X1 
X 
X 
  
lgD/lgE15 
X 
 
 
 
 
 
 
X1 
X 
X 
 
Imaging for Extramedullary 
Disease16 
X 
 
 
 
 
 
 
X1, 16 (Q12W) 
X 
X 
(Q12W) 
 
PET-CT upon achieving MRD 
negativity by NGS 
 
 
 
 
 
 
 
To be performed ONCE after 
achieving MRD negativity by NGS, 
within 42 days (6 weeks) of testing 
negative 
 
Skeletal Survey17 
X 
As clinically indicated 
Response Assessment by 
IMWG18 
 
 
 
 
 
 
 
X1 
X 
X 
 

 
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Protocol Amendment 7 JPN-1 
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22 
Schedule of Activities – Treatment Arm A (Belantamab Mafodotin/Bortezomib/Dexamethasone) 
Procedure 
Screening 
(-28days) 
Treatment Period (±3 days) 
End of Treatment 
(EOT) 
Follow up 
Cycle /  
Visit 
C1 
C2-8 
C1-8  
C1-8  
C1-8  
C9 + 
Fixed Visits 
Q3W 
(Starting at 
Week 4) 
 
PFS 
Follow-
up 
Visit 
Q3W 
(±3 
days) 
OS 
Follow-
up Visit 
Q12W 
(±14 
days) 
Day 
 
D1 
D4 
D8 
D11 
D1 
 
 
 
 
Bone Marrow Assessments19 
BM Biopsy and Aspirate for 
BCMA Expression and Biomarker 
Research 
Please refer to Table 3 for detailed schedule for BM collection procedures at all timepoints, including Screening. 
 
BM Aspirate for FISH Testing 
BM Aspirate/Biopsy for Disease 
Assessments  
BM Aspirate for MRD Testing 
BM Biopsy to Confirm sCR by 
IHC 
Optional BM and/or Tissue 
Sample at PD for BCMA 
Expression and Biomarker 
Research 2 
 
Treatments Administered 
Belantamab mafodotin20 
 
X 
X 
 
 
 
X 
 
 
 
 
Bortezomib21 
 
X 
X 
X 
X 
X 
 
 
 
 
 
Dexamethasone 
 
Days 1, 2, 4, 5, 8, 9, 11 and 12 of each 21-Day cycle 
for Cycles 1 through 8.  
Dose modifications will follow guidance in Section 6.6. 
 
 
 
 
 
Supportive Medication 
 
Supportive medication to be provided for each agent as per institutional guidelines, see Section 6.5.  
 
 
Dispense/Return Medication 
Diary22 
 
X 
X 
 
 
 
X 
 
X 
 
 

 
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23 
Schedule of Activities – Treatment Arm A (Belantamab Mafodotin/Bortezomib/Dexamethasone) 
Procedure 
Screening 
(-28days) 
Treatment Period (±3 days) 
End of Treatment 
(EOT) 
Follow up 
Cycle /  
Visit 
C1 
C2-8 
C1-8  
C1-8  
C1-8  
C9 + 
Fixed Visits 
Q3W 
(Starting at 
Week 4) 
 
PFS 
Follow-
up 
Visit 
Q3W 
(±3 
days) 
OS 
Follow-
up Visit 
Q12W 
(±14 
days) 
Day 
 
D1 
D4 
D8 
D11 
D1 
 
 
 
 
Ocular Supportive Care for Belantamab Mafodotin 
Preservative-free Artificial Tears 
 
4 to 8 times daily in each eye. Daily beginning on Cycle 1 Day 1 until EOT. Allow 5-10 min between 
administration of artificial tears and steroid eye drops, if administered together. In the event of ocular 
symptoms (i.e., dry eyes), the use of artificial tears may be increased up to every 2 hours, as needed.  
 
 
Cooling Eye Masks 
 
May apply to both eyes for as long as tolerated up to 4 hours 
 
 
Health Outcomes 
PRO-CTCAE23 
 
X 
 
 
 
 
 
X 
X 
 
 
EORTC QLQ-C3023 
 
X 
 
 
 
 
 
X 
X 
X 
X23 
EORTC IL5223 
 
X 
 
 
 
 
 
X 
X 
X 
X23 
EQ-5D-3L 
 
X 
 
 
 
 
 
X (Q6W) 
X 
X 
X23 
PGIS 
 
X 
 
 
 
 
 
X (Q6W) 
X 
X 
 
PGIC 
 
X 
 
 
 
 
 
X (Q6W) 
X 
X 
 
FACT-GP523 
 
X 
 
 
 
 
 
X 
X 
X 
 
OSDI24 
 
X 
 
 
 
 
 
X (Q6W) 
X 
X 
X 
Healthcare Resource Utilization 
 
X 
 
 
 
 
 
X1 
 
 
 
Pharmacokinetics and ADA 
Pharmacokinetics25 
 
X (See Table 20 and Table 
21) 
 
 
 
X (See Table 20 
and Table 21) 
 
X 
 
 
ADA25 
 
X (See Section 8.6) 
 
 
 
X (See Section 
8.6) 
 
X 
 
 
Biomarkers19 
Soluble BCMA25, 26 
X 
See Section 8.9.1, Table 22 and Table 23 
 
 
Plasma cfDNA 
 
X 
(predose) 
At every MRD assessment and EOT. For enhanced PK cohort collect also Q12W after 
C1D1 until EOT 
 
 

 
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Schedule of Activities – Treatment Arm A (Belantamab Mafodotin/Bortezomib/Dexamethasone) 
Procedure 
Screening 
(-28days) 
Treatment Period (±3 days) 
End of Treatment 
(EOT) 
Follow up 
Cycle /  
Visit 
C1 
C2-8 
C1-8  
C1-8  
C1-8  
C9 + 
Fixed Visits 
Q3W 
(Starting at 
Week 4) 
 
PFS 
Follow-
up 
Visit 
Q3W 
(±3 
days) 
OS 
Follow-
up Visit 
Q12W 
(±14 
days) 
Day 
 
D1 
D4 
D8 
D11 
D1 
 
 
 
 
Genetics 
Optional Genetic Sample2 
 
X 
 
 
 
 
 
 
 
 
 
ADA = Anti-drug antibody; BM= Bone marrow; BCMA= B-cell maturation antigen; C1D1 = Cycle 1 Day 1, etc.; cfDNA = Circulating free DNA; CR = Complete response; ECG = 
Electrocardiogram; ECOG = Eastern Cooperative Oncology Group; eGFR = Estimated glomerular filtration rate; EOI = End of Infusion; EORTC QLQ-C30  = European Organization for 
Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core module; EORTC IL 52 = European Organization for Research and Treatment of Cancer Item Library 52; 
FISH = Fluorescence in-situ hybridization; EOT = End of Treatment; FLC = Free light chain; FSH = Follicle-stimulating hormone; IHC = Immunohistochemistry; IMWG = International 
Myeloma Working Group; IP = Investigational Product; IV = Intravenous; MRD = Minimal residual disease; OS = Overall Survival; OSDI = Ocular Surface Disease Index; NGS = Next-
generation sequencing; PD = Progressive disease; PGIC= Patient Global Impression of Change; PGIS= Patient Global Impression of Severity; PK = Pharmacokinetics; PRO-CTCAE = 
Patient-Reported Outcomes Version of the Common Term Criteria for Adverse Events; SAE = Serious adverse event; sCR = Stringent Complete Response; SPD = Sum of the 
Products of the maximal perpendicular Diameters; SRM = Study Reference Manual; VGPR= Very Good Partial Response; WOCBP = Women of childbearing potential. 
1. 
To be performed regardless of dosing. 
2. 
Informed consent must be signed before any study specific assessments are performed; the day the informed consent form is signed will be counted as Day 1 and the screening 
window of 28 days will initiate on this Day 1 as well. Assessments performed as standard of care prior to signing consent need not be repeated if done within the appropriate 
screening window. A separate informed consent required for optional samples. For optional samples, a blood sample will be taken at C1D1. The blood sample may be collected at 
another visit if not taken at C1D1. A redraw can be requested if the sample is lost, damaged, or of insufficient quality to perform the analysis. 
3. 
Physical exam must be within 72 hours prior to the first dose of study drugs to be administered in that cycle.  
4. 
C1D1 ocular exam does not need to be repeated if performed within 28 days of screening exam. Participants will be assessed by a qualified eye care specialist (Appendix 10) at 
screening/baseline and then Q3W prior to dosing up to the sixth dose of belantamab mafodotin (assessment window of up to 5 days prior to dosing, but all effort should be made 
to schedule as close to belantamab mafodotin dosing as possible). If there are no significant ocular examinations findings, patient’s symptoms or vision changes at or prior to the 
time of the sixth dose exam, participants may have their ophthalmologic exams decreased to once every 3 months. If a participant subsequently develops vision changes or other 
ocular symptoms, the participant should be promptly evaluated by a qualified eye care specialist. In case of persistent ophthalmic exam findings, newly developed ocular 
symptoms or vision changes at the sixth dose exam, the participants will have further ophthalmologic exams, at least every cycle until resolution (to Grade 1 or baseline) or more 
frequently as clinically indicated by the qualified eye care specialist. See Section 8.2.6 for full details of ocular exam procedures. Participants who have treatment-related ocular 
AEs present at the end of treatment will continue to be followed by qualified eye care specialist at least every 3 months, for up to 12 months or until resolution (to Grade 1 or 
baseline), whichever comes first. 

 
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5. 
For belantamab mafodotin: C1D1 vital signs must be assessed within 30 mins prior to Start of Infusion (SOI), 15 mins after SOI (±10 min), within 15 min after End of Infusion 
(EOI), and at 1 hour (±10 min) after EOI. On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 mins prior to SOI) and within 15 min after EOI, and as 
clinically indicated. On days where vital sign time points align with blood sampling time points, vital signs should be assessed prior to blood samples being drawn.  
Vital signs should be assessed for bortezomib as clinically indicated. See Section 8.2.3 for full details of vital signs. 
6. 
Single ECG. 
7. 
GSK may request that updated survival data be collected on all treated/randomized participants outside the protocol window noted in the SoA. At the time of the request, the site 
will determine survival status for each participant by the method agreed with the participant, unless the participant has withdrawn consent for survival follow-up. Where permitted, 
data from publically available death registers will be used for participants withdrawn from study or lost to follow-up prior to death. 
8. 
All laboratory tests with values considered clinically significantly abnormal during participation in the study or at least 70 days after the last dose of study treatment should be 
repeated until the values return to normal or baseline. See Table 19 for list of comprehensive list of lab tests that must be collected for all participants  
9. 
Hematology and clinical chemistry must be repeated if not within 72 hours prior to first dose of study drugs to be administered in Cycle 1. For Cycles 2 to 8, haematology and 
chemistry must be repeated, if not within 24 hours prior to each dose of study drugs. Starting at Cycle 9, hematology and chemistry must be repeated if not within 24 hours prior to 
each dose of belantamab mafodotin. On Day 1 of any planned cycle, Absolute Neutrophil Count (ANC) must be ≥1.0×109/L to administer treatment. Results must be evaluated 
prior to treatment administration. 
10. Hematology, chemistry and vital signs (as clinically indicated) must be repeated if not within 24 hours prior to each dose of bortezomib, except for C1D1 as the tests are done 
within 72 hours prior to the first dose. 
11. As calculated by Modified Diet in Renal Disease (MDRD) formula (Appendix 7).  
12. Urine dipstick for protein may be used to assess for presence of urine protein. Urine dipstick should be performed at a local lab. Albumin/creatinine ratio needs to be done in any 
participant with urine dipstick protein result of ≥1+ (at screening visit), or ≥2+ (during study treatment), or with positive protein if urine dipstick protein quantification is not available. 
Albumin/creatinine will be performed at a local lab. If local testing is not available, then central testing will be performed (first void). Spot Urine (albumin/creatinine) testing does not 
need to be repeated on i) C1D1 if conducted within 7 days of C1D1 dosing (in case of screening assessment), and  
ii) D1 of subsequent cycles if conducted within 5 days of D1 dosing of a given cycle (C2 onwards). 
Results must be received prior to dosing.  
13. Hepatitis C RNA testing will be done to determine a participant's eligibility if Hep C Ab is positive. This will be performed at a local lab, or if not available then at a central lab. 
Results must be received prior to dosing. For additional procedures during Screening and upon enrollment for participants who have a history of Hepatitis B and/or Hepatitis C, 
please refer to Table 4 and Table 5, respectively. 
14. Perform only on women of childbearing potential (WOCBP). A serum pregnancy test must be performed at screening; if the test is completed within 72 hours prior to the first dose 
of belantamab mafodotin, this assessment does not have to be repeated on C1D1. For questionable cases, follicle-stimulating hormone (FSH) and estradiol should be performed 
at local lab to determine childbearing potential. WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours of dosing on C1D1. Subsequent pregnancy 
tests on dosing days may be either serum or urine. Final pregnancy test (serum or urine) must be performed in WOCBP at the EOT Visit and repeated at least 70 days after last 
dose. Follow up pregnancy assessment by telephone (for WOCBP only) should be performed 4 months after the last dose of belantamab mafodotin or 7 months after the last dose 
of bortezomib, whichever is longest. 
15. Only in participants with IgD/lgE myeloma 
16. Imaging is only required for participants with known extramedullary disease or if there is a suspected appearance of a new lesion. Screening assessments may be performed up to 
30 days prior to C1D1. Subsequent imaging should be performed Q12W (7 days) and then if clinically indicated by either CT, MRI, or PET-CT per local guidance. Needs to be 
performed by the same method throughout the study as was done at baseline. Selected target lesion needs to be measured and followed over time. Plasmacytoma measurements 
should be taken from the CT portion of the PET-CT, or MRI scans, or dedicated CT scans where applicable. For participants with only skin involvement, skin lesions should be 

 
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measured with a ruler. Measurement of tumor size will be determined by the SPD of measured lesions.  
Participants undergoing PET-CT should have all blood samples taken before the PET-CT is performed. 
For participants with PD due to extramedullary disease, confirmatory scans are not required. The laboratory parameters do not need to be repeated if the extramedullary disease 
is the only site of progression. If the last radiographic assessment occurred ≥8 weeks prior to the participant’s withdrawal from study treatment, and PD has NOT been 
documented, a new assessment for extramedullary disease should be obtained at EOT. If participant continues in PFS follow-up, perform scans for extramedullary disease as 
clinically indicated. 
Digital copies of all scans must be maintained at Investigator site as source document. 
17. Survey results within 30 days prior to C1D1 date are acceptable. Imaging of bones for lytic lesions should be performed by a method aligned with institutional guidance (i.e., X-ray, 
CT or MRI). At later Cycles, repeat as clinically indicated, or if worsening clinical symptoms suggest PD. Needs to be performed by the same method throughout the study as was 
done at baseline. 
18. Response to treatment will be assessed, based on laboratory tests and imaging (if applicable), using the International Myeloma Working Group (IMWG) criteria [Kumar, 2016].  
19. All biomarker and BM samples (biopsy and aspirate), once collected, will be analyzed if the sample date and time have been recorded. 
20. Belantamab mafodotin administration: belantamab mafodotin 2.5 mg/kg, Q3W will be administered as an IV infusion (see Pharmacy Manual for details), followed by a 1-hour 
observation period. A window of ±3 days is acceptable for administration of belantamab mafodotin after C1D1. At least 21 days should elapse between consecutive doses of 
belantamab mafodotin. Please refer to Section 6.6.1 for instructions on dose delays. 
21. If a bortezomib dose was delayed, subsequent doses should be adjusted to account for delay as all bortezomib doses must be at least 72 hours/3 calendar days apart. Doses that 
need to be withheld are skipped and will not be made up later in the cycle. Individual doses within a cycle have a ±1-day window. 
22. Participant diary will be used to keep a record of self-administered dexamethasone. 
23. PRO-CTCAE, EORTC QLQ-C30, FACT-GP5, and EORTC IL52 should be collected Q3W, prior to any treatment administration on C1D1 and all subsequent visits. EQ-5D-3L, 
PGIC, and PGIS should be administered Q6W on treatment. EORTC QLQ-C30, EORTC IL52 and EQ-5D should be collected at 3, 6 and 12 months during OS follow up (can be 
collected by phones using interviewer administration). 
24. OSDI should be collected at C1D1, then Q3W up to the 6th DOSE of belantamab mafodotin, then Q6W onward until EOT.  In addition, all participants will complete the OSDI at 
the EOT visit. Participants with no treatment-related ocular AEs per CTCAE v5.0 for corneal events at the EOT ocular assessment will have no further OSDI collection. 
Participants with treatment-related ocular AEs per CTCAE v5.0 for corneal events at the EOT ocular assessment will have OSDI collected Q12W until resolution (to Grade 1 or 
baseline) OR for up to 12 months, whichever is sooner. 
25. PK, PK-associated sBCMA and ADA sample collection is relative to dose of belantamab mafodotin, which is independent of cycle number to account for the possibility that 
belantamab mafodotin may be held whilst other agents continue. ADA samples are collected pre-dose only. All PK, sBCMA, and ADA samples, once collected (regardless of 
dosing), will be analysed if the sample date and time have been recorded. 
26. See Section 8.9.1, Table 22 and Table 23 for sBCMA schedules. Also, sBCMA should be collected at screening, and when there is a PK-associated sBCMA sample collection in 
which case only the PK sample needs to be collected (only 1 sample needed). Likewise, collect sBCMA at the end of treatment.  
 
 

 
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Table 2 
Schedule of Activities - Treatment Arm B (Daratumumab/Bortezomib/Dexamethasone) 
• 
Screening assessments do not need to be repeated on C1D1 if conducted within 72 hours of C1D1 dosing, unless otherwise specified.  
• 
The 28-day Screening period is initiated upon signature of the informed consent form (Day 1). The full 28 days can be taken to determine the eligibility of the participants. 
Participants can be randomized during or upon completion of the 28 days i.e. the day after the Screening period has ended. Study treatment (C1D1) should be initiated within 
72 hours after randomization.  
• 
Precise timing of treatment cycles may vary due to treatment delays, but participants must still visit for efficacy assessments regularly regardless of when they receive 
treatment. The schedule for efficacy assessments is Q3W. These are referred to as ‘fixed visits’ or ‘weeks visits’ and should be scheduled from C1D1. 
• 
Assessments scheduled on days of dosing should be done prior to drug administration unless otherwise specified. All assessments should be carried out even if a participant is 
not dosed except for the following:  vital signs, weight, pregnancy test and PK where applicable.  
• 
End of Treatment (EOT) visit will occur within 30 days from the last cycle, or prior to initiation of new anti-myeloma therapy (whichever occurs first). AEs and SAEs will be 
collected up to at least 70 days after the last dose, either via phone or a follow up visit. Participants who have ocular symptoms at EOT will be followed up for ocular exams and 
OSDI questionnaire as described in Section 8.2.6. After discontinuation of study treatment, the participant should continue disease assessments as per the SoA.  Every effort 
should be made to confirm disease progression per the IMWG criteria prior to initiating a new anti-myeloma therapy. 
• 
PFS follow-up: Participants who permanently discontinue study treatment for reasons other than disease progression will remain in the study and will be followed for PFS 
according to the protocol schedule until: 
o 
Disease progression according to IMWG criteria (move to Survival follow-up) 
o 
New anti-myeloma therapy is initiated (move to Survival follow-up) 
o 
Death 
o 
Withdrawal of consent 
o 
Loss to follow-up 
o 
End of study 
• 
Survival follow-up: Participants will be followed for survival and subsequent anti-myeloma therapy (PFS2) by chart review, phone call, or any form of communication every 12 
weeks (14-day window) beginning from the last q3w assessment visit until death, withdrawal of consent, lost to follow-up or end of the study, whichever comes first. 
Subsequent visits should be 12 weeks (14-day window) from the date of contact of the prior survival follow-up visit. Participant does not need to come in for visit unless they 
are being followed for treatment-related changes in vision that are present at the EOT. Record the participant’s survival status and whether subsequent treatment for disease 
was given. 
• 
GSK may request that updated survival data be collected on all treated/randomized participants outside the protocol window noted in the Schedule of Assessments. At the time 
of the request, the site will determine survival status for each participant by the method agreed with the participant, unless the participant has withdrawn consent for survival 
follow-up. Where permitted, data from publicly available death registers will be used for participants withdrawn from study or lost to follow-up prior to death. 
• 
For details on Home Healthcare and Telemedicine Approaches, please refer to Appendix 15. 
 

 
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Schedule of Activities - Treatment Arm B: Daratumumab/Bortezomib/Dexamethasone 
Procedure 
 
Treatment Period (±3 days for Q3W visits)    
End of Treatment  
(EOT) 
Follow up 
Cycle /Visit 
Screening  
(-28 days) 
C1-3 
(Dara) 
C1 
(Bor) 
  
C2-8  
(Bor)
 
 
C4-8 
(Dara) 
C1-8  
(Bor) 
C1-8  
(Bor) 
C1-8  
(Bor) 
C9 +  
Fixed Visits 
Q3W (Starting 
at Week 4) 
 
PFS 
Follow-up Visit 
Q3W (±3 days) 
OS Follow-up 
Visit Q12W 
(±14 days) 
Day 
 
D1, D8, 
D15 
D1 
D4 
D8 
D11 
D1 
Informed Consent1, 2 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Baseline Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/Disease History and 
Characteristics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Body Weight 
X 
 
X 
X 
 
 
 
 
X 
 
X 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Safety 
Physical Exam3 
X 
X (D1 
only) 
X 
X 
X 
 
 
 
X 
 
X 
X 
 
ECOG Performance Status 
X 
X (D1 
only) 
X 
X 
X 
 
 
 
X 
 
X 
X 
 
Ocular Exam4 
X 
X4  
(see 
footnot
e) 
 
 
X4 (see 
footnot
e) 
 
 
 
X4 (see 
footnote) 
X4 (see 
footnote) 
X 
X4 
X4 
Vital Signs (BP, Heart rate, 
Body Temp)5 
X 
X 
X 
X 
X 
If clinically indicated 
X 
 
X 
 
 
12-Lead ECG6 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Adverse Events/SAEs 
 
Adverse events and SAEs will be collected throughout the study until at least 70 days after the last dose. SAEs related to study participation are collected 
from time of consent until end of study. See Section 8.3.1. 
Concomitant Medications  
Concomitant medications will be collected, as reported by the participant or through participant medical record review. 
Survival Follow-up Phone call7 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Laboratory Assessments8 
Hematology9,10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X1 
X 
X 
 
Clinical Chemistry9,10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X1 
X 
X 
 
HbA1c 
As clinically indicated 
 
eGFR11 
X 
 
X 
 
 
 
 
 
 
X1 
X 
 
 
Urine dipstick OR Spot Urine 
(Albumin/Creatinine ratio12) 
X 
 
X 
 
 
 
 
 
 
X1 
X 
 
 

 
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Schedule of Activities - Treatment Arm B: Daratumumab/Bortezomib/Dexamethasone 
Procedure 
 
Treatment Period (±3 days for Q3W visits)    
End of Treatment  
(EOT) 
Follow up 
Cycle /Visit 
Screening  
(-28 days) 
C1-3 
(Dara) 
C1 
(Bor) 
  
C2-8  
(Bor)
 
 
C4-8 
(Dara) 
C1-8  
(Bor) 
C1-8  
(Bor) 
C1-8  
(Bor) 
C9 +  
Fixed Visits 
Q3W (Starting 
at Week 4) 
 
PFS 
Follow-up Visit 
Q3W (±3 days) 
OS Follow-up 
Visit Q12W 
(±14 days) 
Day 
 
D1, D8, 
D15 
D1 
D4 
D8 
D11 
D1 
HbsAg, HbcAb, Hep C Ab, Hep 
C RNA13 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Indirect antiglobulin test 
(Indirect Coombs test)  
X 
 
Blood type and screen 
X 
 
Daratumumab-specific 
immunofixation assay14 
 
X15 
 
 
 
 
 
 
 
X15 
X 
X 
 
Pregnancy Test for WOCBP16 
X 
 
X 
X 
 
 
 
 
X 
 
X 
X16 
X16 
Disease Evaluations:  Baseline disease assessments completed within 28 days (30 days for imaging) of C1D1 do not need to be repeated on C1D1. For participants who are discontinuing IP due to 
PD, confirmation based on laboratory parameters must be performed from a different sample collection (serum/urine) before institution of any new anti-myeloma therapy and preferably within 14 days 
of the date of the initial assessment showing unconfirmed disease progression. This may be performed at the EOT visit.  
β2 Microglobulin 
X 
 
 
 
 
 
 
 
 
 
 
 
 
SPEP (Serum Protein 
Electrophoresis) 
X 
 
 
 
 
 
 
 
 
X1 
X 
X 
 
UPEP (Urine Protein 
Electrophoresis) (on 24-hour 
collected urine)  
X 
 
 
 
 
 
 
 
 
X1 
X 
X 
 
Serum M Protein Calculation 
X 
 
 
 
 
 
 
 
 
X1 
X 
X 
 
Serum Kappa Lambda Free LC, 
FLC Ratio 
X 
 
 
 
 
 
 
 
 
X1 
X 
X 
 
Serum Immunofixation 
X 
 
 
Serum immunofixation must be performed each time that M-protein is not quantifiable by SPEP (0 g/dL) 
Urine immunofixation must be performed each time that M-protein is not quantifiable by UPEP (0 mg/24 hr) AND 
SPEP (0 g/dL) 
 
Urine Immunofixation 
X 
 
 
Calcium Corrected for Albumin 
(serum) 
X 
 
 
 
 
 
 
 
 
X1 
X 
X 
 
lgG, lgM, lgA 
X 
 
 
 
 
 
 
 
 
X1 
X 
X 
 
lgD/lgE17 
X 
 
 
 
 
 
 
 
 
X1 
X 
X 
 
Imaging for Extramedullary 
Disease18 
X 
 
 
 
 
 
 
 
 
X1, 18 (Q12W) 
X 
X (Q12W) 
 

 
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Schedule of Activities - Treatment Arm B: Daratumumab/Bortezomib/Dexamethasone 
Procedure 
 
Treatment Period (±3 days for Q3W visits)    
End of Treatment  
(EOT) 
Follow up 
Cycle /Visit 
Screening  
(-28 days) 
C1-3 
(Dara) 
C1 
(Bor) 
  
C2-8  
(Bor)
 
 
C4-8 
(Dara) 
C1-8  
(Bor) 
C1-8  
(Bor) 
C1-8  
(Bor) 
C9 +  
Fixed Visits 
Q3W (Starting 
at Week 4) 
 
PFS 
Follow-up Visit 
Q3W (±3 days) 
OS Follow-up 
Visit Q12W 
(±14 days) 
Day 
 
D1, D8, 
D15 
D1 
D4 
D8 
D11 
D1 
PET-CT upon achieving MRD 
negativity by NGS 
 
 
 
 
 
 
 
 
 
To be performed ONCE after achieving 
MRD negativity by NGS, within 42 days 
(6 weeks) of testing negative 
 
Skeletal Survey19 
X 
 
 
 
As clinically indicated 
Response Assessment by 
IMWG20 
 
 
 
 
 
 
 
 
 
X1 
X 
X 
 
Bone Marrow Assessments21 
BM Biopsy and Aspirate for 
BCMA Expression and 
Biomarker Research 
Please refer to Table 3 for detailed schedule for BM collection procedures at all timepoints, including Screening.  
 
BM Aspirate for FISH Testing 
BM Aspirate/Biopsy for Disease 
Assessments  
BM Aspirate for MRD Testing 
BM Biopsy to Confirm sCR by 
IHC 
Optional BM and/or Tissue 
Sample at PD for BCMA 
Expression and Biomarker 
Research 2 
Treatments Administered  
Daratumumab22 
 
X 
 
 
X 
 
 
 
X (Q4W) 
 
 
 
 
Bortezomib23 
 
 
X 
X 
 
X 
X 
X 
 
 
 
 
 
Dexamethasone 
 
Days 1, 2, 4, 5, 8, 9, 11 and 12 of each 21-Day cycle for 
 Cycles 1 through 8.  
Dose modifications will follow guidance in Section 6.6. 
 
 
 
 
 
Supportive Medication 
Supportive medication to be provided for each agent as per institutional guidelines, see Section 6.5.  
 
 
Dispense/Return Medication 
Diary24 
 
 
X 
X 
 
 
 
 
X 
 
X 
 
 

 
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Schedule of Activities - Treatment Arm B: Daratumumab/Bortezomib/Dexamethasone 
Procedure 
 
Treatment Period (±3 days for Q3W visits)    
End of Treatment  
(EOT) 
Follow up 
Cycle /Visit 
Screening  
(-28 days) 
C1-3 
(Dara) 
C1 
(Bor) 
  
C2-8  
(Bor)
 
 
C4-8 
(Dara) 
C1-8  
(Bor) 
C1-8  
(Bor) 
C1-8  
(Bor) 
C9 +  
Fixed Visits 
Q3W (Starting 
at Week 4) 
 
PFS 
Follow-up Visit 
Q3W (±3 days) 
OS Follow-up 
Visit Q12W 
(±14 days) 
Day 
 
D1, D8, 
D15 
D1 
D4 
D8 
D11 
D1 
Health Outcomes 
PRO-CTCAE25 
 
 
X 
 
 
 
 
 
 
X 
X 
 
 
EORTC QLQ-C3025 
 
 
X 
 
 
 
 
 
 
X 
X 
X 
X25 
EORTC IL5225 
 
 
X 
 
 
 
 
 
 
X 
X 
X 
X25 
EQ-5D-3L 
 
 
X 
 
 
 
 
 
 
X (Q6W) 
X 
X 
X25 
PGIS 
 
 
X 
 
 
 
 
 
 
X (Q6W) 
X 
X 
 
PGIC 
 
 
X 
 
 
 
 
 
 
X (Q6W) 
X 
X 
 
FACT-GP525 
 
 
X 
 
 
 
 
 
 
X 
X 
X 
 
OSDI26 
 
 
X 
 
 
 
 
 
 
X (Q12W) 
X 
 
 
Healthcare Resource Utilization 
 
 
X 
 
 
 
 
 
 
X1 
 
 
 
Biomarkers21 
Soluble BCMA27 
X 
 
See Table 24 in Section 8.9.1 
 
 
Plasma cfDNA 
 
 
X 
(pre-
dose) 
At every MRD assessment timepoint 
 
X 
 
 
Genetics 
Optional Genetic Sample2 
 
 
X 
 
 
 
 
 
 
 
 
 
 
ADA = Anti-drug antibody; BM= Bone marrow; BCMA= B-cell maturation antigen; C1D1 = Cycle 1 Day 1, etc.; cfDNA = Circulating free DNA; CR = Complete response; ECG = 
Electrocardiogram; ECOG = Eastern Cooperative Oncology Group; eGFR = Estimated glomerular filtration rate; EOI = End of Infusion; EORTC QLQ-C30  = European Organization for 
Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core module; EORTC IL52 = European Organization for Research and Treatment of Cancer Item Library 52; 
FISH = Fluorescence-in-situ hybridization; EOT = End of Treatment; FLC = Free light chain; FSH = Follicle-stimulating hormone; IHC = Immunohistochemistry; IMWG = International 
Myeloma Working Group; IP = Investigational product; MRD = Minimal residual disease; OS = Overall Survival; OSDI = Ocular Surface Disease Index; NGS = Next-generation 
sequencing; PD = Progressive disease; PGIC= Patient Global Impression of Change; PGIS= Patient Global Impression of Severity;  PK = Pharmacokinetics; PRO-CTCAE = Patient-
Reported Outcomes Version of the Common Term Criteria for Adverse Events; SAE = Serious adverse event; sCR = Stringent Complete Response; VGPR= Very Good Partial 
Response; WOCBP = Women of childbearing potential. 
 
1. 
To be performed regardless of dosing.  
2. 
Informed consent must be signed before any study specific assessments are performed; the day the informed consent form is signed will be counted as Day 1 and the screening 
window of 28 days will initiate on this Day 1 as well. Assessments performed as standard of care assessment prior to signing consent need not be repeated if done within the 

 
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appropriate screening window. Separate consent required for optional samples. For optional sample, a blood sample will be taken at C1D1. The blood sample may be collected at 
another visit if not taken at C1D1. A redraw can be requested if the sample is lost, damaged, or of insufficient quality to perform the analysis. 
3. 
Physical exam must be within 72 hours prior to the first dose of study drugs to be administered in that cycle.  
4. 
C1D1 ocular exam does not need to be repeated if performed within 28 days of screening exam. Ocular exam may be performed up to 5 days prior to dosing. On treatment ocular 
exams to be performed at Cycle 6 and then decreased to every 6 months (4 week window) until and including eye exam at end of treatment. If a participant subsequently 
develops vision changes or other ocular symptoms, the participant should be promptly evaluated by a qualified eye care specialist. In case of persistent ophthalmic exam findings, 
newly developed ocular symptoms or vision changes, the participants will have further ophthalmologic exams, at least every cycle until resolution (to Grade 1 or baseline) or more 
frequently as clinically indicated by the qualified eye care specialist (Appendix 10). Participants who have treatment-related ocular AEs present at the end of treatment will 
continue to be followed by qualified eye care specialist at least every 3 months, for up to 12 months or until resolution (to Grade 1 or baseline), whichever comes first. See Section 
8.2.6.2 for full details of ocular exam procedures. 
5. 
On days where vital sign time points align with blood sampling time points, vital signs should be assessed prior to blood samples being drawn. On days where vital signs are 
measured multiple times, temperature does not need to be repeated unless clinically indicated. Vital signs should be assessed for bortezomib as clinically indicated. Blood 
pressure and heart rate are to be measured at the following time points at the time of first daratumumab administration: 
– Within 30 min prior to Start of Infusion (SOI) 
– At 30 mins, 2 hours, and 3 hours 30 min after SOI (±10 mins);  
– Within 15 min of End of Infusion (EOI) 
– 30 min, 1 hour, and 2 hours after EOI (±10 mins)  
On Cycle 1 Day 1, if daratumumab administration is split and given over Day 1 and Day 2, vital signs are to be measured on both Day 1 and Day 2 as per above time points. 
For all other daratumumab infusions, blood pressure will be measured within 30 min prior to SOI and within 15 min after EOI, and as clinically indicated. See Section 8.2.3.2 for full 
details of vital signs. 
6. 
Single ECG. 
7. 
GSK may request that updated survival data be collected on all treated/randomized participants outside the protocol window noted in the SoA. At the time of the request, the site 
will determine survival status for each participant by the method agreed with the participant, unless the participant has withdrawn consent for survival follow-up. Where permitted, 
data from publically available death registers will be used for participants withdrawn from study or lost to follow-up prior to death. 
8. 
All laboratory tests with values considered clinically significantly abnormal during participation in the study or at least 70 days after the last dose of study treatment should be 
repeated until the values return to normal or baseline. Refer to Table 19 for a comprehensive list of lab tests that must be collected for all participants. 
9. 
Hematology and chemical chemistry must be repeated if not within 72 hours prior to first dose of study drugs to be administered in Cycle 1. Hematology and clinical chemistry are 
to be performed every cycle up to 72 hours prior to every daratumumab administration. Results must be evaluated prior to treatment administration. Refer to Table 19 for a 
comprehensive list of lab tests that must be collected for all participants. 
10. Hematology, clinical chemistry and vital signs (as clinically indicated) must be repeated if not within 24 hours prior to each dose of bortezomib, except for C1D1 as the tests are 
done within 72 hours prior to the first dose. When bortezomib administration coincides with and Daratumumab administration, hematology, clinical chemistry, and vital signs (as 
clinically indicated) will be performed within 24 hours prior to dosing. 
11. As calculated by Modified Diet in Renal Disease (MDRD) formula (Appendix 7).  
12. Urine dipstick for protein may be used to assess for presence of urine protein. Urine dipstick should be performed at a local lab. Albumin/creatinine ratio needs to be done in any 
participant with Urine dipstick protein result of ≥1+ (at screening visit), or ≥2+ (during study treatment), or with positive protein if urine dipstick protein quantification is not 
available. Albumin/creatinine will be performed at a local lab. If local testing is not available, then central testing will be performed (first void). In case of Screening assessment, 
Spot Urine (albumin/creatinine) testing does not need to be repeated on C1D1 if conducted within 7 days of C1D1 dosing. Results must be received prior to dosing.  

 
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13. Hepatitis C RNA testing will be done to determine a participant's eligibility if Hep C Ab is positive. This will be performed at a local lab, or if not available then at a central lab. 
Results must be received prior to dosing. For additional procedures during Screening and upon enrollment for participants who have a history of Hepatitis B and/or Hepatitis C, 
please refer to Table 4 and Table 5, respectively.  
14. Participants with IgG kappa myeloma and disease response of CR with suspected PD, or disease response of VGPR with suspected CR, are required to undergo central testing 
with a daratumumab-specific immunofixation assay to confirm PD or CR/sCR. 
15. First sample to be collected only on Day 1 of Cycle 1, prior to dosing; subsequent samples will be collected at each fixed visit Q3W starting at Week 4. 
16. Perform only on women of childbearing potential (WOCBP). A serum pregnancy test must be performed at screening; if the test is completed within 72 hours prior to the first dose 
of daratumumab, this assessment does not have to be repeated on C1D1. For questionable cases, follicle-stimulating hormone (FSH) and estradiol should be performed at local 
lab to determine childbearing potential. WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours of dosing on C1D1. Subsequent pregnancy tests on 
dosing days may be either serum or urine. Final pregnancy test (serum or urine) must be performed in WOCBP at the EOT Visit and repeated at least 70 days after last dose). 
Follow up pregnancy assessment by telephone (for WOCBP only) should be performed 7 months after the last dose of bortezomib or 3 months from the last dose of 
daratumumab, whichever is longest. 
17. Only in participants with IgD/lgE myeloma 
18. Imaging is only required for participants with known extramedullary disease or if there is a suspected appearance of a new lesion. Screening assessments may be performed up to 
30 days prior to C1D1. Subsequent imaging should be performed at Q12W(7 days) and then if clinically indicated by either CT, MRI, or PET-CT per local guidance. Needs to be 
performed by the same method throughout the study as was done at baseline. Selected target lesion needs to be measured and followed over time. Plasmacytoma measurements 
should be taken from the CT portion of the PET-CT, or MRI scans, or dedicated CT scans where applicable. For participants with only skin involvement, skin lesions should be 
measured with a ruler. Measurement of tumor size will be determined by the SPD of measured lesions.  
Participants undergoing PET-CT should have all blood samples taken before the PET-CT is performed. 
For participants with PD due to extramedullary disease, confirmatory scans are not required. The laboratory parameters do not need to be repeated if the extramedullary disease 
is the only site of progression. If the last radiographic assessment occurred ≥8 weeks prior to the participant’s withdrawal from study treatment, and PD has NOT been 
documented, a new assessment for extramedullary disease should be obtained at EOT. If participant continues in PFS follow-up, perform scans for extramedullary disease as 
clinically indicated. 
Digital copies of all scans must be maintained at Investigator site as source document. 
19. Survey results within 30 days prior to C1D1 date are acceptable. Imaging of bones for lytic lesions should be performed by a method aligned with institutional guidance (i.e., X-ray, 
CT or MRI). At later Cycles, repeat as clinically indicated, or if worsening clinical symptoms suggest PD. Needs to be performed by the same method throughout the study as was 
done at baseline. 
20. Response to treatment will be assessed, based on laboratory tests and imaging (if applicable), using the International Myeloma Working Group (IMWG) criteria [Kumar, 2016] 
21. All biomarker and BM samples (biopsy and aspirate), once collected, will be analyzed if the sample date and time have been recorded. 
22. Daratumumab 16 mg/kg IV. Corticosteroid should be administered prior to daratumumab infusion unless prior intolerance. On days when daratumumab coincides with 
dexamethasone, dexamethasone is sufficient as the pre-infusion corticosteroid. On days when daratumumab does not coincide with dexamethasone an additional pre-infusion 
corticosteroid should be given. The Week 1 dose of daratumumab ONLY may be administered as a single infusion or a split infusion over 2 days, according to the local/regional 
label and institutional guidelines (for details see Section 6.1.4). 
23. If a bortezomib dose was delayed, subsequent doses should be adjusted to account for delay as all bortezomib doses must be at least 72 hours/3 calendar days apart. Doses that 
need to be withheld are skipped and will not be made up later in the cycle. Individual doses within a cycle have a ±1-day window. 
24. Participant diary will be used to keep a record of self-administered dexamethasone. 

 
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25. PRO-CTCAE, EORTC QLQ-C30, FACT-GP5, and EORTC IL52 should be collected Q3W, prior to any treatment administration on C1D1 and all subsequent visits. EQ-5D-3L, 
PGIC, and PGIS should be administered Q6W on treatment. EORTC QLQ-C30, EORTC IL52 and EQ-5D should be collected at 3, 6 and 12 months during OS follow up (can be 
collected by phones using interviewer administration).  
26. OSDI should be collected at C1D1, then Q3W up to the 6th cycle, then Q12W onward until EOT.  In addition, all participants will complete the OSDI at the EOT visit.  
27. See Section 8.9.1, Table 24 for sBCMA collection schedule. sBCMA should be collected at screening and at the end of treatment.  
 

 
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Table 3 
Bone Marrow Aspirate/Biopsy Collection (Treatment Arm A and Treatment Arm B) 
Timepoint  
BM aspirate for 
disease 
assessmenta,d  
BM biopsy for 
disease 
assessmenta,d  
BM aspirate for 
FISH testinga,e  
BM aspirate for MRD 
testingb,f 
BM aspirate and biopsy for 
BCMA expression and 
biomarker researchb,g 
Optional BM and/or tissue 
sample at PD for BCMA 
expression and biomarker 
researchb,h 
Screening 
Xc 
Xc 
X  
X  
X  
  
VGPR or better 
  
  
 
X  
 
  
Suspected CR/sCR 
Xd  
Xd 
 
X  
 
  
Suspected PD, 
only if PD is not 
otherwise evident  
Xc  
Xc  
 
  
X  
 
At PD 
 
 
 
 
 
X 
BCMA = B-cell maturation antigen; BM = bone marrow; CR = complete response; FISH = fluorescence in situ hybridization; MRD = minimal residual disease; PD = progressive 
disease; sCR = stringent complete response; VGPR = very good partial response.  
a. 
These assessments will be performed at a local laboratory. 
b. 
These assessments will be performed at a central laboratory.  
c. 
For Disease assessment: BM aspirate and/or biopsy per institutional practice. 
d. 
For sCR in participants achieving a CR, a bone marrow core biopsy is required to confirm sCR by IHC for absence of clonal cells. Only 1 bone marrow procedure required for 
CR and sCR assessment. If testing cannot be performed at a local lab, the samples can be sent to the central lab. 
e. 
FISH testing to be performed locally at least for: t(4;14), t(14;16), amp(1q), del(1p) and del(17p13). If participant is known to have tested positive for t(4;14) or t(14;16) on previous 
tests, FISH for those translocations does not need to be repeated and results from previous tests are acceptable regardless of when those tests were performed. For amp(1q), 
del(1p) and del(17p13), FISH results from samples taken within 60 days prior to first dose are acceptable. If testing cannot be performed at a local lab, the samples can be sent to 
the central lab. FISH results are required prior to randomization. 
f. 
Minimal residual disease (MRD) testing to be performed at Screening and at the time of first achieving VGPR or better (i.e. achieving CR without prior VGPR). Thereafter, MRD 
testing must be repeated every 6 months (1 month) from the time of last sample collection until PD. In case of deepening of response from VGPR to suspected CR, MRD testing 
must be performed at the time of achieving suspected CR and repeated every 6 months from the time of last sample collection until PD.  
g. 
BM core biopsy and aspirate samples to be collected at Screening for BCMA expression and biomarker research. BM biopsy is the preferred sample for these exploratory 
analyses. Every effort should be made to collect a BM biopsy for this test, however, if for any reason BM biopsy is not obtainable, then an aspirate must be collected for BCMA 
expression and biomarker research. Any remaining biopsy and/or aspirate sample will be used for biomarker research (which may include immune cell characterization and/or 
profiling and/or DNA/RNA analyses). 
h. 
Optional BM core biopsy and/or aspirate and/or tissue sample (if from extramedullary tumor) for BCMA expression and biomarker research may be collected at PD to evaluate 
mechanisms of response/resistance. Separate consent required for this optional sample at PD. 

 
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Table 4 
Hepatitis B (HBV) SoA – Additional Procedures 
Note: The procedures listed in this table apply ONLY to participants in screening and who have been enrolled and who have a history of Hepatitis B; all procedures must be done as 
needed in addition to the required procedures for all participants detailed in Table 1 and Table 2 
HBV Study Assessments 
During Screening / 
Prior to starting 
treatment 
During Treatment 
EOT 
Notes 
HBV related Liver Imaging3 
X1 
X1 
X1 
1. 
Liver imaging (specific test per standard of care at local institution) in HBsAg+ 
participants to rule-out/identify cirrhosis, focal hepatic lesions, and/or biliary 
abnormalities at baseline. Repeat imaging at one year after starting treatment if 
still on treatment and twice yearly thereafter as long as participant remains on 
study treatment or as clinically indicated. 
2. 
HBV-DNA testing prior to the start of study treatment and subsequently every 3 
months, or if LFT elevations requiring increased monitoring or stopping criteria 
occur, or for any clinical suspicion of hepatitis reactivation.   
3. 
For HBsAg+ participants, appropriate antiviral treatment per local guidance 
(e.g. tenofovir or entecavir) is started before starting study treatment, continues 
through to completion of treatment and should not be stopped unless advised 
by local hepatology or virology services. 
HBV-DNA testing 
X2 
X2 
X2 
Prevention of HBV 
reactivation 
X3 
X3 
X3 
 
HBsAg = Hepatitis B surface antigen; HBV = Hepatitis B; LFT = liver function test 

 
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Table 5 
Hepatitis C (HCV) SoA – Additional Procedures 
Note: The procedures listed in this table apply ONLY to participants in screening and who have been enrolled and who have a history of Hepatitis C; all procedures must be done as 
needed in addition to the required procedures for all participants detailed in Table 1 and Table 2. 
HCV Study Assessments 
During Screening / 
Prior to starting 
treatment 
During 
Treatment 
Post Treatment 
Notes 
HCV-RNA testing 
X1 
X1 
 
1. 
HCV- RNA testing prior to the start of study treatment and subsequently every 3 
months, or if LFT elevations requiring increased monitoring or stopping criteria 
occurs, or for any clinical suspicion of hepatitis reactivation.  
2. 
Antiviral treatment should be given to participants with HCV before enrolment 
using an 8 (to 12) week antiviral treatment course with curative intent per local 
guidance. HCV RNA should be negative at 4 weeks washout period post anti-HCV 
therapy prior to enrolment. 
Treatment of active HCV  
X2 
 
 
 
HCV = Hepatitis C virus 
 

 
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2. 
INTRODUCTION 
2.1. 
Study Rationale 
Multiple myeloma (MM) is an incurable malignancy and accounts for 1% of all cancers 
and for 10% of all hematologic malignancies. Worldwide, approximately 139,000 new 
cases are diagnosed annually [Cowan, 2018], and an estimated 30,770 new cases and 
12,770 deaths will occur in the U.S. in 2018 [Siegel, 2019]. Despite significant advances, 
current novel therapies and hematopoietic stem cell transplant (HSCT) cannot achieve 
cure, and most MM participants will die of disease progression or complications of 
myeloma. Thus, new treatments are urgently needed. 
B-cell maturation antigen (BCMA) is a target present on mature B cells and on tumour 
cells in patients with MM [Tai, 2015; Tai, 2006]. Belantamab mafodotin is an antibody-
drug conjugate (ADC) consisting of a humanized anti-BCMA monoclonal antibody 
(mAb) that is conjugated to the microtubule inhibitor monomethyl auristatin-F (MMAF) 
with a maleimidocaproyl linker (cysteine maleimidocaproyl MMAF [cys-mcMMAF]; 
also, known as SGD-1362). 
Belantamab mafodotin binds to BCMA and kills MM cells via a multi-modal mechanism 
including delivery of cytotoxic, cys-mcMMAF to BCMA-expressing MM cells, thereby 
inducing apoptosis, enhancing antibody-dependent cellular cytotoxicity and antibody-
dependent cellular phagocytosis, and inducing immunogenic cell death (Figure 1) [Tai, 
2014; Montes De Oca, 2019]. Exposure of dendritic cells to tumour cells undergoing 
immunogenic cell death is expected to result in a tumour antigen-specific T-cell response, 
enhancing the immunogenic response against MM. 
Of the 4 proposed MoA for belantamab mafodotin, the ADC and ADCC MoAs have 
been linked to efficacy in non-clinical models: in vitro and in vivo against multiple 
myeloma cell lines, and ex vivo against primary patient myeloma samples. Inhibition of 
BCMA signalling has been demonstrated biochemically; however, functional effects on 
myeloma cells have not been demonstrated. ICD markers on cells are induced by 
belantamab mafodotin both in vivo and in vitro. In vivo, induction of ICD correlates with 
an adaptive immune response and long-term tumour regression in immune-competent 
murine allograft models. These different mechanisms may enable belantamab mafodotin 
to deliver anti-tumour activities targeting both dividing and nondividing tumour cells and 
associate the cell kill with an adaptive immune response. These MoA characteristics 
clearly differentiate belantamab mafodotin from existing approved treatments. Several 
assets targeting BCMA by different mechanisms are in clinical development for MM, 
including BCMA CAR-T cells and BCMA bispecific antibodies. However, none of the 
currently approved therapies for MM have the same MoAs as belantamab mafodotin. 
Despite new medicines in a relapsed refractory population providing clinical benefit, 
multiple myeloma is not currently curable and an unmet need still remains. Belantamab 
mafodotin has shown strong single-agent activity in the first time in human (FTIH) study 
(BMA117159). Among the 35 participants receiving belantamab mafodotin at 3.4 mg/kg 
IV, Q3W, with a median of 5 prior therapies, the ORR was 60% (95% CI: 42.1%, 
76.1%); the median PFS was 12.0 months (95% CI: 3.1, -NE months) and the duration of 

 
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response, not previously estimable at the interim analyses, was estimated at 14.3 months 
[Trudel, 2019]. Due to novel MoAs, it is possible that belantamab mafodotin may be able 
to overcome resistance to existing therapies. 
In Study BMA117159, the maximum clinical benefit (ORR) was observed at the 
3.4 mg/kg dose level, but a significant number of participants required dose delays and 
dose reductions to manage adverse events. In phase II Study 205678, belantamab 
mafodotin was further evaluated as monotherapy in RRMM patients at the dose of 
2.5 mg/kg and 3.4 mg/kg Q3W and based on benefit/risk assessment, a dose of 2.5 mg/kg 
Q3W has been proposed as the monotherapy dose. This dose of 2.5 mg/kg Q3W has been 
further evaluated in combination with bortezomib and dexamethasone in Study 207497 
and based on the safety evaluation, this dose has been selected for this study. 
The efficacy for belantamab mafodotin monotherapy is reviewed in the Investigator’s 
Brochure (IB) (see Section 2.2.4) [GSK document No. RPS-CLIN-105644]. 
Given this previous experience, the combination of belantamab mafodotin with other 
therapies with different MoA is an attractive option to explore for patients with MM who 
have relapsed or become refractory to standard of care (SoC). The combination with 
other agents may result in additive, or potentially synergistic effects which could translate 
into deep and long-lasting responses. 
It is hypothesized that the combination of belantamab mafodotin and bor/dex will lead to 
greater patient benefit, as measured by progression-free survival (PFS), compared to the 
SoC combination of daratumumab and bor/dex. While there are some potential overlaps 
in the pattern of identified toxicities between belantamab mafodotin and bor/dex 
(primarily hematologic), they are expected to be manageable. 
2.2. 
Background 
2.2.1. 
Current Treatment of Multiple Myeloma 
Most, if not all patients treated with myeloma regimens inevitably relapse, with a median 
overall survival (OS)  of about 5 years [Robinson, 2014; Hou, 2017; Palumbo, 2015]. 
Each relapse requires salvage therapy, and the duration of response (DoR) to each 
subsequent line of salvage therapy typically decreases. For example, in a retrospective 
chart review of patients who become refractory to bortezomib and IMIDs, the median OS 
time was disappointingly short (~ 9 months), with 7% achieving VGPR, 24% achieving 
partial response (PR), and 10% with stable disease after retreatment [Kumar, 2012]. 
While the main treatment goal for RRMM is usually the preservation of organ function, 
control of the disease, and maintaining quality of life, the depth of response is also 
considered a predictor of durability of response and patient survival [Lonial, 2014]. 
While combining agents with existing SoC therapies might be a straightforward 
approach, an alternative strategy to achieving deep responses is to evaluate combinations 
of agents that have preclinical evidence or scientific rationale for enhancing the clinical 
benefit of belantamab mafodotin.  

 
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2.2.2. 
Role of B-Cell Maturation Antigen in Multiple Myeloma. 
BCMA, also designated as tumour necrosis factor receptor superfamily member 17 
(TNFRSF17) is expressed on the surface of normal and malignant B lymphocytes at later 
stages of differentiation as they mature [Novak, 2004]. Ligands targeting BCMA such as 
B-cell activating factor of the tumour necrosis factor family (BAFF), TNFSF13B, along 
with A proliferation-inducing ligand (APRIL/TNFSF13) activate cell proliferation 
pathways and upregulate anti-apoptotic proteins in MM cell lines [Bellucci, 2005, 
Moreaux, 2004]. Soluble BCMA (sBCMA) is present in the serum of MM patients, and 
its levels have been postulated to correlate with tumour burden, response to therapy and 
OS [Robinson, 2014; Sanchez, 2012]. Mice deficient for BCMA are viable, have normal 
B-cell development, and exhibit normal humoral responses [Belnoue, 2008; Jiang, 2011; 
Varfolomeev, 2004]. BCMA is widely expressed on malignant plasma cells in MM and 
to a lesser degree in other B-cell malignancies [Tai, 2015; Tai, 2006]. The restricted 
expression profile of BCMA makes it a very good target for a therapeutic antibody with 
direct cell killing activity and expected to have limited off target effects [Tai, 2015]. 
BCMA has been validated as a therapeutic target in MM in preclinical studies [Tai, 2014] 
and more recently in the clinic, where impressive results were demonstrated with BCMA-
targeted Chimeric Antigen T cell therapy (CAR-T) [Pont, 2019], and belantamab 
mafodotin as single agent [GSK document No. RPS-CLIN-105644; Trudel, 2018; Trudel, 
2019]. 
2.2.3. 
Antibody-Drug Conjugate Belantamab Mafodotin 
Belantamab mafodotin is a humanized (IgG1) ADC which binds specifically to BCMA 
with different mechanisms of action as detailed in the IB [GSK document No. RPS-
CLIN-105644]. 
Of the 4 proposed MoAs for belantamab mafodotin, the ADC and ADCC MoAs have 
been linked to efficacy in non-clinical models:  in vitro and in vivo against multiple 
myeloma cell lines, and ex vivo against primary patient myeloma samples. These 
different mechanisms may enable belantamab mafodotin to deliver anti-tumour activities 
targeting both dividing and nondividing tumour cells and associate the cell kill with an 
adaptive immune response; these MoA characteristics clearly differentiate belantamab 
mafodotin from existing approved treatments. All patients with MM express various 
levels of BCMA on the surface of the tumour cells, making them potentially responsive 
to treatment with belantamab mafodotin [Darce, 2007]. 

 
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Figure 1 
Mechanism of Action of Belantamab Mafodotin 
 
ADCC/ADCP=antibody-dependent cell-mediated cytotoxicity/antibody-dependent 
cellular phagocytosis 
  
2.2.4. 
Clinical Experience with Belantamab Mafodotin 
Single-agent belantamab mafodotin has demonstrated to have a strong single-agent 
activity with a well-defined manageable safety profile in heavily pre-treated participants 
with RRMM (Q3W schedule via IV administration). Safety data for single-agent 
belantamab mafodotin were pooled (data as of 20 September 2019) for study 205678 
(DREAMM-2; NCT03525678) and supportive FTIH study BMA117159 (DREAMM-1; 
NCT02064387), by treatment cohorts of 2.5 mg/kg and 3.4 mg/kg. 
FTIH study BMA117159/DREAMM-1 
In the FTIH DREAMM-1 study, which consisted of a dose escalation phase (Part 1, 
n=38) and a dose expansion phase (Part 2, n=35), as of the primary analysis cut-off date 
of 31 August 2018, a total of 73 participants with RRMM received at least 1 dose of 
belantamab mafodotin [GSK document No. RPS-CLIN-105644; Trudel, 2019]. 

 
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As of the efficacy cut-off date of 31 August 2018, a total of 35 participants were treated 
at the 3.4 mg/kg dose in Part 2 of the DREAMM-1 study. Participants were heavily pre-
treated: 57% of participants had 5 or more prior lines of therapy. The ORR was 60% 
(95% CI: 42.1, 76.1): comprised of PR, 6%; VGPR, 40%; CR, 9%; and stringent CR 
(sCR), 6%. The median duration of response (DoR) was 14.3 months (95% CI: 10.6, 
NR). The median PFS (mPFS) in this population was 12.0 months (95% CI: 3.1, not 
estimable [NE]). For participants refractory to both IMiDs and PIs (n = 32/35), the 
confirmed ORR was 56% (95% CI: 37.7, 73.6) and mPFS was 7.9 months (95% CI: 2.3, 
NE) [Trudel, 2019]. 
Phase II study 205678/DREAMM-2 
DREAMM-2 is a Phase II, randomized, 2-arm open-label study evaluating the efficacy 
and safety of belantamab mafodotin monotherapy (Blenrep), given at 2.5 mg/kg or 
3.4 mg/kg IV once every 3 weeks in adult patients with relapsed or refractory multiple 
myeloma.  Study participants had previously received 3 or more prior lines of 
anti-myeloma therapy, including an anti-CD38 antibody, and were refractory to an 
immunomodulatory agent and a proteasome inhibitor. A total of 196 participants were 
treated in the 2 dose cohorts, 97 in the 2.5 mg/kg cohort and 99 in the 3.4 mg/kg cohort. 
In the primary analysis, the ORR assessed by an independent review committee was 31% 
(97.5% CI: 20.8, 42.6) in the 2.5 mg/kg cohort and 34% (97.5% CI: 23.9, 46.0) in the 
3.4 mg/kg cohort. 
The final analysis of the study (Data Cut-off Date: 31 March 2022) confirmed the 
efficacy and safety results of the primary analysis. The ORR was 32% (97.5% CI: 
21.7,43.6) in the 2.5 mg/kg cohort and 35% (97.5% CI: 24.8, 47.0) in the 3.4 mg/kg 
cohort. More than half of responders (58% and 69%) had a response of VGPR or better. 
The median duration of response was 12.5 months (95% CI: 4.2,19.3) in the 2.5 mg/kg 
cohort and 6.2 months (95% CI: 4.8,18.7) at 3.4 mg/kg cohort. The median PFS was 2.8 
months (95% CI: 1.6, 3.6) and 3.9 months (95% CI: 2.0, 5.8), respectively. The median 
OS was 15.3 months (95% CI: 9.9, 18.9) in the 2.5 mg/kg cohort and 14.0 months (95% 
CI: 10.0, 18.1) in the 3.4 mg/kg cohort. 
Key safety data of the DREAMM-2 study include the following (data for 2.5 mg/kg 
cohort are presented first, followed by the 3.4 mg/kg cohort): Serious adverse events 
(SAE) occurred in 45% and 54% of participants, of which 15% and 21% were related to 
study treatment. SAE in >3% of participants in either cohort included pneumonia (7% 
and 14%), pyrexia (7% and 5%), and hypercalcemia (4% and none). Fatal SAEs related 
to study treatment occurred in 1% and 2% of participants, including sepsis (1%), cardiac 
arrest (1%), and lung infection (1%). Grade 3 or 4 AEs related to study treatment were 
reported in 58% and 64% of the participants. The most common treatment-related Grade 
2 AEs reported were keratopathy (59% and 64%), thrombocytopenia (14% and 27%), 
vision blurred (13% and 18%), infusion related reaction (13% and 5%), anemia (6% and 
10%), and neutropenia (4% and 10%). The most common AEs (≥25%) were keratopathy, 
thrombocytopenia, anemia, nausea, vision blurred, and pyrexia.  Infusion-related 
reactions of any Grade occurred in 21% and 16% of participants, including Grade 3 in 
3% and 1%. 

 
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Permanent discontinuation due to AEs occurred in 12% of participants in both cohorts of 
which 9% and 5% were considered treatment related. Keratopathy (3% each in both 
cohorts) was the most frequent AEs resulting in permanent discontinuation. Dose 
interruptions due to an AE occurred in 54% and 62% of participants. Dose reductions due 
to an AE occurred in 36% and 44% of participants. AEs which required a dose reduction 
in >3% of patients included keratopathy (28% and 30%) and thrombocytopenia (4% and 
11%). The most common Grade 3 or 4 (≥10%) laboratory abnormalities were decreases 
of lymphocytes, platelet count, haemoglobin, neutrophils, and leukocytes, and increases 
in gamma-glutamyl transferase values. 
2.2.4.1. 
Pharmacokinetics and Pharmacodynamics in Humans 
The pharmacokinetics and pharmacodynamics of belantamab mafodotin (antibody-drug 
conjugate, including complex with sBCMA), and total monoclonal antibody (total mAb; 
including complex), and cys-mcMMAF were investigated in 291 participants with 
RRMM following IV administration at doses from 0.03 to 4.6 mg/kg Q3W in Study 
BMA117159 (n=73) and at doses of 2.5 or 3.4 mg/kg Q3W in Study 205678 (n=218). 
Maximum concentrations (Cmax) of belantamab mafodotin and total monoclonal 
antibody were observed at or shortly after the end of infusion (EOI), while cys-mcMMAF 
Cmax values were generally observed on Day 2. On a molar basis, plasma concentrations 
of cys-mcMMAF were <1% of belantamab mafodotin concentrations. There was limited 
accumulation (less than 2-fold) of belantamab mafodotin or cys-mcMMAF during 
subsequent cycles.  
Belantamab mafodotin pharmacokinetics were well described by a linear, 2-compartment 
population model, with a time-varying decrease in clearance in a population 
pharmacokinetic analysis. At Cycle 1, belantamab mafodotin had a systemic clearance of 
0.92 L/day, steady-state volume of distribution of 10.8 L, and an elimination half-life of 
12 days in participants with RRMM in Study 205678. Over time, clearance was reduced 
by 28%, resulting in an elimination half-life of 14 days. The time to 50% change in 
clearance was approximately 50 days.  
No clinically significant differences in the pharmacokinetics of belantamab mafodotin or 
cys-mcMMAF were observed based on age (34 to 89 years), sex, race (African 
American/Black and White), body weight (42 to 130 kg), mild or moderate renal 
impairment (eGFR ≥ 30 ml/min/1.73m2) or mild hepatic impairment (NCI-ODWG 
classification). Higher serum levels of 2-microglobulin, IgG, and soluble BCMA 
(sBCMA) and lower levels of albumin are associated with more advanced multiple 
myeloma or a higher multiple myeloma disease burden. Higher baseline IgG and sBCMA 
levels, and lower baseline albumin levels were associated with higher belantamab 
mafodotin clearance leading to lower average and trough concentrations (Ctau) of 
belantamab mafodotin. Higher baseline IgG and sBCMA levels were associated with 
higher cys-mcMMAF central volume of distribution leading to lower cys-mcMMAF 
Cmax. 
In nonclinical studies, cys-mcMMAF had limited metabolic clearance. In vitro data 
suggested that belantamab mafodotin and cys-mcMMAF are unlikely to perpetrate a 
drug-drug interaction or to be a victim of a drug-drug interaction with inhibitors or 

 
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inducers of cytochromes (CYP) P450. Cys-mcMMAF was an in vitro substrate of organic 
anion transporting polypeptides (OATP)1B1 and OATP1B3, multidrug resistance 
associated proteins (MRP)1, MRP2, and MRP3, a borderline substrate of bile salt export 
pump (BSEP), and a possible substrate of P-glycoprotein (P-gp). Following the 
administration of belantamab mafodotin to participants with RRMM, only intact cys-
mcMMAF was detected in pooled human urine, with no evidence of other MMAF-
related urinary metabolites.  
Free sBCMA levels were measured in Study BMA117159 and Study 205678. All 
participants exhibited reductions in free sBCMA concentration at end of infusion 
compared to baseline at Cycle 1, with a return to near-baseline level by 7 days after 
dosing, reflecting binding of belantamab mafodotin to sBCMA. 
 
 
  
Exposure-response analyses performed for Study 205678 and/or Study BMA117159 
found that ocular safety endpoints were most strongly associated with belantamab 
mafodotin exposure, while efficacy endpoints had a weaker association with belantamab 
mafodotin exposure. Both safety and efficacy endpoints were associated with patient 
characteristics. Belantamab mafodotin Ctau was associated with probability of corneal 
events and keratopathy and cys-mcMMAF Cmax was associated with probability of 
thrombocytopenia. Probability of occurrence of dry eye, blurred vision, neutropenia and 
infusion related reaction were not associated with an exposure measure. In addition, the 
results of the analysis of concentration against corrected QT interval (QTc) demonstrated 
that belantamab mafodotin or cys-mcMMAF did not have a significant effect on cardiac 
repolarization. 
Additional information related to belantamab mafodotin clinical PK, PD, and exposure-
response relationships can be found in the IB [GSK document No. RPS-CLIN-105644]. 
CCI

 
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2.3. 
Benefit/Risk Assessment 
2.3.1. 
Summary of Risk Assessment for Belantamab Mafodotin (Treatment Arm A), Daratumumab (Treatment 
Arm B), and Bor/Dex (Treatment Arms A and B) 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Potential Overlapping Toxicities of Belantamab mafodotin/Bortezomib/Dexamethasone (Treatment Arm A) 
Thrombocytopenia 
Belantamab mafodotin: Belantamab mafodotin may cause transient 
thrombocytopenia in some participants, which for most cases recovered 
between doses. 
In study 205678 which included participants treated with belantamab 
mafodotin 2.5 mg/kg, thrombocytopenia was noted in 38% of participants 
and ranged between Grade 1 to 4 in severity. 
Bortezomib: Associated with thrombocytopenia that follows a cyclical 
pattern with nadirs occurring following the last dose of each cycle and 
typically recovering prior to initiation of subsequent cycle. 
Routine monitoring of hematologic panels as outlined in the SoA. 
Supportive therapy per local medical practice (e.g., platelet transfusion, 
growth factors). 
Recommendations for dose reduction and treatment discontinuation criteria 
are detailed in Section 6.6 and Section 7. 
Pneumonitis 
Belantamab mafodotin: Nonclinical safety experiments have 
demonstrated the presence of progressive microscopic changes in the 
lungs (prominent alveolar macrophages associated with eosinophilic 
material; mixed perivascular inflammation) in rats, at all doses tested. 
Cases of pneumonitis, including fatal events, have been observed with 
belantamab mafodotin although a causal association has not been 
established. 
Bortezomib: Acute Respiratory Distress Syndrome and acute diffuse 
infiltrative pulmonary disease of unknown etiology, such as pneumonitis, 
interstitial pneumonia, and lung infiltration have been reported rarely in 
patients receiving bortezomib. Some of these events have been fatal.  
There have been reports of pulmonary hypertension associated with 
bortezomib administration in the absence of left heart failure or significant 
pulmonary disease. 
Monitoring for clinical signs and symptoms related to pulmonary toxicity. If 
a participant experiences new or worsening pulmonary symptoms, (e.g., 
cough, dyspnea) without obvious etiology, further diagnostic tests and 
management should be performed and further treatment with belantamab 
mafodotin delayed (refer to Section 6).  
An overall benefit/risk assessment should be considered for the participant 
prior to continuing belantamab mafodotin treatment.  
Further diagnostic tests and management will be implemented immediately 
in cases of suspected pneumonitis as described in Section 6.6.1 in Table 
10. 
In the event of new or worsening cardiopulmonary symptoms, consider 
interrupting bortezomib until a prompt and comprehensive diagnostic 
evaluation is conducted. 

 
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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Increased Infections 
due to 
immunosuppression or 
neutropenia 
Belantamab mafodotin: In nonclinical studies, belantamab mafodotin 
has been associated with decrease in immunoglobulins in monkeys, at all 
doses. An increase in immunoglobulins was seen in rats (rats are not an 
antigen specific species for belantamab mafodotin). 
Immunosuppression is frequently associated with an increased risk of 
infection. Serious and non-serious infections have been reported in 
belantamab mafodotin studies, including respiratory infections, 
pneumonia, and sepsis. 
Neutropenic events, including febrile neutropenia have been observed 
with belantamab mafodotin. 
Bortezomib: Cases of herpes zoster reactivation and infection have been 
reported in patients receiving bortezomib. Associated with neutropenia 
that follows a cyclical pattern with nadirs occurring following the last dose 
of each cycle and typically recovering prior to initiation of subsequent 
cycle 
Dexamethasone: Patients who are on corticosteroids are more 
susceptible to infections or exacerbation of latent infections than healthy 
individuals. Chickenpox and measles can have a more serious or even 
fatal course in pediatric and adult patients on corticosteroids. 
Participants with an active infection are excluded. 
Monitoring for infections and immediate treatment of immunosupression 
according to standard practice. 
Supportive therapy per local medical practice (e.g. growth factors). 
Prophylactic antibiotics, per local institutional guidance, in participants with 
Grade 3-4 neutropenia. 
Immediate hospitalization of participants with febrile neutropenia. 
Participants on bortezomib will receive antiviral prophylaxis (e.g. acyclovir 
or other antiviral agent) according to institutional guidelines. 
If exposed to chickenpox, prophylaxis with varicella zoster immune globulin 
(VZIG) may be indicated. If exposed to measles, prophylaxis with immune 
globulin may be indicated. 
Dose modification guidelines are provided in Section 6. 
Keratopathy (changes 
to the corneal 
epithelium, potentially 
resulting in vision 
changes) 
Belantamab mafodotin: Changes in corneal epithelium on ocular 
examination have been frequently observed with belantamab mafodotin 
and was most commonly associated with keratopathy (changes in the 
corneal epithelium upon examination), dry eyes, photophobia, blurred 
vision and changes in visual acuity. 
Participants with a history of dry eye were more prone to develop 
changes in the corneal epithelium. 
Based on available follow-up data, vision returned to, or near baseline in 
most cases. 
Active monitoring of the corneal epithelium and visual acuity as outlined in 
the SoA.  
Evaluation and management by an eye care professional. 
Recommendations for dose delays / reductions and treatment stopping 
guidance are provided in Section 7.1.3 and Table 11 

 
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Mitigation Strategy 
Dexamethasone: Use of corticosteroids may produce posterior 
subcapsular cataracts, glaucoma with possible damage to the optic 
nerves, and may enhance the establishment of secondary ocular 
infections due to bacteria, fungi, or viruses. 
Risks Related to Belantamab Mafodotin (not listed under potential overlapping toxicity) 
Infusion-related 
Reactions (IRR) 
IRRs were reported in participants treated with belantamab mafodotin. 
Most IRRs were Grade 1 to 2 and manageable with medical treatment. 
Close monitoring for signs of IRR. 
Consider premedication for IRR. 
If an IRR occurs, follow the guidance in Section 7.1.4. 
Nephrotoxicity 
Non-clinical safety experiments have demonstrated primary glomerular 
injury and tubular degeneration/regeneration (in rat and monkey). These 
morphologic changes were accompanied by large molecular weight 
proteinuria (albuminuria) and enzymuria. Single cell necrosis of the kidney 
and bladder urothelium was also noted in the chronic study. The renal 
changes were dose-dependent and reversible. Severe tubular 
degeneration/regeneration and marked glomerulonephritis as a result of 
immune complex disease associated with ADA led to the early euthanasia 
of 1 monkey following 5 weekly doses of 10 mg/kg. 
Increase albumin/creatinine ratio (albuminuria) has been reported in 
participants receiving belantamab mafodotin not indicative of disease 
progression, and in such cases, appropriate monitoring and dose 
modification should be considered. 
Kidney function monitoring including albumin/creatinine ratio. 
Education of participants on the need to maintain adequate urinary output. 
Dose modification criteria for increased serum creatinine and urinary 
albumin/creatinine ratio are provided in Section 7. 
Risks Related to Daratumumab  
IRR 
Severe and/or serious infusion reactions, including anaphylactic 
reactions. 
Premedicate with antihistamines, antipyretics and corticosteroids as 
detailed in Section 6.1.4.1. and monitor participants during infusion.  
Interrupt daratumumab infusion for reactions of any severity and institute 
medical management as needed. 

 
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Recommendations for dose delays / reductions and treatment stopping 
guidance are provided in Section 7.1.4. 
Post-medicate patients with corticosteroid according to the guidance laid 
out in Section 6.1.4.1. 
Interference with 
Serological Testing 
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a 
positive indirect antiglobulin test (Indirect Coombs test), which may persist 
for up to 6 months after the last daratumumab infusion. Daratumumab 
bound to RBCs masks detection of antibodies to minor antigens in the 
patient’s serum. Determination of ABO and Rh blood type not impacted. 
Participants receiving daratumumab will be typed and screened prior to 
daratumumab administration.  
 
Thrombocytopenia/ 
Neutropenia 
Daratumumab may increase neutropenia and thrombocytopenia induced 
by background therapy. 
Hematologic panels will be routinely assessed as outlined in the SoA. 
Viral Infections, 
Especially Herpes 
Zoster 
Cases of herpes zoster infection have been reported in patients receiving 
daratumumab. 
Patients assigned to Treatment Arm B will receive antiviral prophylaxis (for 
example acyclovir or other according to institutional guidelines) from C1D1 
until 3 months after the completion of daratumumab treatment. 
Risks Related to Bortezomib (not listed under potential overlapping toxicity with belantamab mafodotin) 
Allergic Reactions 
Bortezomib is contraindicated for patients with hypersensitivity to 
bortezomib, boron, or mannitol, including anaphylactic reactions. 
Participants with known hypersensitivity reactions to bortezomib, boron, or 
mannitol are not allowed on study. 
Bortezomib will be discontinued if such reactions are confirmed. 
Peripheral Neuropathy 
Bortezomib treatment causes a peripheral neuropathy that is 
predominantly sensory; however, cases of severe sensory and motor 
peripheral neuropathy have been reported. 
Participants with Grade 2 peripheral neuropathy at Screening excluded 
from study participation. 
Monitor for symptoms of neuropathy. Dose will be adjusted accordingly. 
Bortezomib administered subcutaneously to reduce risk of peripheral 
neuropathy. 

 
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Hypotension 
Incidence of hypotension (postural, orthostatic, and hypotension not 
otherwise specified [NOS]) was 8%. 
Participants with a history of syncope, or receiving medications associated 
with hypotension, or dehydrated will be closely monitored. 
Adjustment of antihypertensive medications, hydration, and administration 
of mineralocorticoids and/or sympathomimetics will follow the institutional 
guidelines. 
Posterior Reversible 
Encephalopathy 
Syndrome (PRES) 
PRES; formerly termed Reversible Posterior Leukoencephalopathy 
Syndrome (RPLS) has occurred in patients receiving bortezomib. 
Discontinue bortezomib if PRES occurs. 
The safety of reinitiating bortezomib therapy in patients previously 
experiencing PRES is not known. 
Gastrointestinal 
Toxicity 
Treatment with bortezomib can cause nausea, diarrhea, constipation, and 
vomiting sometimes requiring use of antiemetic and antidiarrheal 
medications; ileus can occur. 
Maintain adequate hydration; fluid and electrolyte replacement should be 
administered to prevent dehydration. 
Interrupt bortezomib for severe symptoms.  
Hepatotoxicity 
Cases of acute liver failure have been reported in patients receiving 
multiple concomitant medications and with serious underlying medical 
conditions. Other reported hepatic reactions include hepatitis, increases in 
liver enzymes, and hyperbilirubinemia. 
Only participants with well-preserved liver function per the 
inclusion/exclusion criteria will be allowed on study. 
Participants with chronic Hepatitis B and C excluded. 
Liver function tests will be monitored per SOA. 
Liver stopping criteria outlined in Section 7.1.2. 
Tumor Lysis Syndrome 
(TLS) 
TLS has been reported with bortezomib therapy. 
Participants at risk for TLS (e.g. high tumor burden) will be monitored and 
appropriate precautions instituted per local practice. 
Thrombotic 
Microangiopathy 
Cases, sometimes fatal, of thrombotic microangiopathy, including 
thrombotic thrombocytopenic purpura/haemolytic uremic syndrome 
(TTP/HUS), have been reported in patients receiving bortezomib. 
Monitor for clinical signs and symptoms potentially related to thrombotic 
microangiopathy. 
If suspected, stop bortezomib and evaluate. If the diagnosis of TTP/HUS is 
excluded, consider restarting bortezomib. 

 
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Potential for 
cardiotoxicity related 
to an inflammatory 
response 
Acute development or exacerbation of congestive heart failure and new 
onset of decreased LVEF have occurred during bortezomib therapy, 
including reports in patients with no risk factors for decreased LVEF. 
 
Participants with significant cardiac risk factors will be excluded from the 
study participation. 
Monitoring of cardiac parameters as clinically indicated. 
Treatment as medically indicated. 
Seizures 
Seizures have been uncommonly reported in patients without previous 
history of seizures or epilepsy.  
Special care is required when treating patients with any risk factors for 
seizures. 
Participants with a history of seizures or epilepsy, will be closely monitored. 
In the event of new onset or worsening seizures, consider interrupting 
bortezomib until a prompt and comprehensive diagnostic evaluation is 
conducted. 
Progressive Multifocal 
Leukoencephalopathy 
(PML) 
Very rare cases with unknown causality of John Cunningham (JC) virus 
infection, resulting in PML and death, have been reported in patients 
treated with bortezomib. Patients diagnosed with PML had prior or 
concurrent immunosuppressive therapy. Most cases of PML were 
diagnosed within 12 months of their first dose of bortezomib.  
Patients should be monitored at regular intervals for any new or worsening 
neurological symptoms or signs that may be suggestive of PML as part of 
the differential diagnosis of CNS problems. If a diagnosis of PML is 
suspected, patients should be referred to a specialist in PML and 
appropriate diagnostic measures for PML should be initiated. Discontinue 
bortezomib if PML is diagnosed. 
Risks Related to Dexamethasone (not listed under overlapping toxicity with belantamab mafodotin) 
Vaccination 
Administration of live or live, attenuated vaccines is contraindicated in 
patients receiving immunosuppressive doses of corticosteroids. 
Killed or inactivated vaccines may be administered. However, the response 
to such vaccines cannot be predicted.  
Immunizations with live/ live-attenuated vaccines are not allowed in the 
study. 
Allergic or 
Hypersensitivity 
Reactions 
Contraindicated in patients who are hypersensitive to any components of 
this product. 
Rare instances of anaphylactoid reactions have occurred in patients 
receiving corticosteroid therapy. 
Enrollment of participants with known hypersensitivity reactions to any 
component of the formulation is prohibited. 

 
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Endocrine 
Hypothalamic-pituitary adrenal axis suppression with the potential for 
corticosteroid insufficiency after withdrawal of treatment. 
Avoid rapid withdrawal of corticosteroids if used at high doses for a 
prolonged period. 
Gastrointestinal 
Use with caution in active or latent peptic ulcers, diverticulitis, fresh 
intestinal anastomoses, and nonspecific ulcerative colitis, since they may 
increase the risk of a perforation, or GI bleeding. 
Hematologic parameters will be monitored as outlined in the SoA.  
New cases of anemia should be fully investigated, including the possibility 
of GI bleeding. 
Musculoskeletal 
Decreased bone formation and increase bone resorption. Acute myopathy 
has been observed with the use of high doses of corticosteroids, most 
often occurring in patients with neuromuscular disorders, or in patients 
receiving neuromuscular blocking drugs. 
Ongoing monitoring of AEs. 
Neuropsychiatric 
Psychic derangements ranging from mild symptoms to severe 
depression, to frank psychotic manifestations. Existing emotional 
instability or psychotic tendencies may be aggravated by corticosteroids. 
Ongoing monitoring of AEs. 
Potential for 
cardiotoxicity  
Average and large doses of corticosteroids can cause elevation of blood 
pressure, sodium and water retention, and increased excretion of 
potassium. 
Participants with significant cardiovascular risk factors will be excluded 
from study participation. 
Risks from Study Procedures  
Bone Marrow 
Aspiration/biopsy 
Pain, infection, bleeding may occur after the procedure. 
Participants will be treated according to institution’s practice. 
Incidental Findings 
During Imaging Data 
Acquisition 
During the acquisition of imaging data (e.g., MRI, PET-CT), non-MM 
disease or drug-related clinical abnormalities could be found by the 
radiographer performing the exams. 
All imaging scans will be reported at the site by a radiographer (non-
anonymized) for non-MM disease or drug-related clinical abnormalities. 
Refer to the belantamab mafodotin Investigator’s Brochure and local/regional prescribing information (where available) for daratumumab, bortezomib and dexamethasone, for 
further information. 
 

 
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2.3.2. 
Benefit Assessment 
The FTIH study BMA117159, as of 31 August 2018, indicated that belantamab 
mafodotin monotherapy administered at 3.4 mg/kg is active in patients with RRMM 
(n=35), with an ORR of 60.0% (95% CI: 42.1, 76.1) and a median PFS was 12.0 months 
(95% CI: 3.1, NR) in a heavily pre-treated population (57% ≥5 prior lines of therapy) 
[Trudel, 2018; Trudel, 2019]. 
In the ongoing Phase II study 205678/DREAMM 2, the 2 single agent doses (2.5 mg/kg 
and 3.4 mg/kg) are being studied via a 2-arm, randomized design in participants who 
have failed at least 3 prior lines of anti-myeloma therapy, including an anti-CD38 
antibody, and who are refractory to an IMiD and a PI. Both dose levels, 2.5 and 3.4 
mg/kg, have a positive benefit/risk profile. Overall, there were no new safety signals 
identified in the 205678 study, and the profile of adverse events was similar to the 
experience in DREAMM-1 for both arms. Primary analysis show both dose levels of 
belantamab mafodotin (2.5 and 3.4 mg/kg) to have a positive benefit/risk profile. The 
dose of 2.5 mg/kg appears to have a lower incidence of adverse events and less frequent 
dose delays and reductions, and it results in similar efficacy with 3.4 mg/kg dose as 
measured by ORR [Lonial, 2020]. 
Increased anti-myeloma activity has been demonstrated when additional agents, with 
individual activity, are given in combination with bortezomib and dexamethasone, 
including monoclonal antibodies. The combination treatment of a highly active drug, 
belantamab mafodotin, with bortezomib and dexamethasone is therefore expected to 
result in increased benefit to MM patients who have relapsed after at least 1 prior line of 
therapy, with improved patient outcomes as measured by progression-free survival. 
The ongoing Phase I/II open-label, dose escalation and expansion study 207497 
(DREAMM 6) is evaluating the safety and clinical activity of belantamab mafodotin 
when given in combination with Lenalidomide/Dexamethasone (Arm A) on a 28-day 
cycle, or with bortezomib/dexamethasone (Arm B) in participants with RRMM who have 
received at least 1 prior line of therapy. For Arm B (GSK2857916 with bor/dex), during 
Part 1 (dose escalation), 
 
 
 
. Part 2 (dose expansion) of the study is further evaluating the safety and 
preliminary clinical activity of both the dose levels (2.5 and 3.4 mg/kg) and up to 2 
dosing schedules of belantamab mafodotin (administered as SINGLE dose on Day 1 of 
each cycle, and administered as 2 equal divided doses a week apart on Day 1 and Day 8 
of each cycle) with bor/dex. 
 
 
 
 
 
For the current study Phase III study 207503, the dose of 2.5 mg/kg of belantamab 
mafodotin has been selected. 
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2.3.3. 
Overall Benefit: Risk Conclusion 
Considering the observed clinical activity of belantamab mafodotin as a single agent in 
participants with RRMM, and the observed safety profile in mono- and combination 
therapy, it is reasonable to assume that the combination of belantamab mafodotin with 
bor/dex may offer additional benefit to patients with RRMM, by improving progression-
free survival. Although there is the potential for overlapping toxicities, it is anticipated 
that belantamab mafodotin/bor/dex treatment will have an acceptable risk/benefit profile, 
with manageable toxicities. Considering the measures taken to minimize risk to 
participants, the potential risks associated with belantamab mafodotin in combination 
with bor/dex are justified by the anticipated benefits that may be afforded to participants 
with MM. 

 
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3. 
OBJECTIVES AND ENDPOINTS 
Objectives 
Endpoints1 
Primary 
The primary objective of this study is to 
compare the efficacy of belantamab 
mafodotin in combination with bortezomib 
and dexamethasone (bor/dex) with that of 
daratumumab in combination with bor/dex 
in participants with RRMM 
• 
Progression-Free Survival (PFS), defined as the time from the 
date of randomization until the earliest date of documented 
disease progression or death due to any cause 
Key Secondary 
To compare the efficacy of belantamab 
mafodotin in combination with bor/dex with 
that of daratumumab in combination with 
bor/dex in participants with RRMM 
• 
Overall Survival (OS), defined as the time from the date of 
randomization until the date of death due to any cause 
 
• 
Duration of Response (DoR), defined as the time from first 
documented evidence of PR or better until progressive disease 
(PD) or death due to any cause 
• 
Minimal Residual Disease (MRD) negativity rate, defined as the 
percentage of participants who are MRD negative by next-
generation sequencing (NGS) 
Secondary 
To further assess the efficacy of 
belantamab mafodotin in combination with 
bor/dex with that of daratumumab in 
combination with bor/dex in terms of other 
efficacy outcomes in participants with 
RRMM 
• Complete Response Rate (CRR), defined as the percentage of 
participants with a confirmed complete response (CR) or better 
(i.e., CR, sCR) 
• Overall Response Rate (ORR), defined as the percentage of 
participants with a confirmed partial response (PR) or better (i.e., 
PR, VGPR, CR, sCR) 
• Clinical Benefit Rate (CBR), defined as the percentage of 
participants with a confirmed minimal response (MR) or better per 
IMWG 
• Time to Response (TTR), defined as the time between the date of 
randomization and the first documented evidence of response 
(PR or better) among participants who achieve confirmed PR or 
better 
• Time to Progression (TTP), defined as the time from the date of 
randomization until the earliest date of documented PD or death 
due to PD 
• PFS2, defined as time from randomization to disease progression 
after initiation of new anti-myeloma therapy or death from any 
cause, whichever is earlier. If disease progression after new anti-
myeloma therapy cannot be measured, a PFS event is defined as 
the date of discontinuation of new anti-myeloma therapy, or death 
from any cause, whichever is earlier 

 
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Objectives 
Endpoints1 
To evaluate the safety and tolerability of 
belantamab mafodotin when administered 
in combination with bor/dex 
• Incidence of adverse events (AEs) and changes in laboratory 
parameters 
• Ocular findings on ophthalmic exam 
To further describe the exposure to 
belantamab mafodotin when administered 
in combination with bor/dex 
• 
Plasma concentrations of belantamab mafodotin, and cys-
mcMMAF 
To assess anti-drug antibodies (ADAs) 
against belantamab mafodotin 
• Incidence and titers of ADAs against belantamab mafodotin 
To evaluate the safety and tolerability of 
belantamab mafodotin based on self-
reported symptomatic adverse effects 
when administered in combination with 
bor/dex 
• Maximum post-baseline PRO-CTCAE score for each item 
attribute 
To evaluate and compare changes in 
symptoms and health-related quality of life 
(HRQOL)  
• Change from baseline in HRQOL as measured by EORTC QLQ-
C30 and EORTC IL52 (disease symptoms domain from the 
EORTC QLQ-MY20) 
Exploratory 
To further assess the efficacy of 
belantamab mafodotin in combination with 
bor/dex with that of daratumumab in 
combination with bor/dex in terms of 
additional efficacy outcomes in 
participants with RRMM 
• Time to Best Response (TTBR), defined as the interval of time 
between the date of randomization and the earliest date of 
achieving best response among participants with a confirmed PR 
or better 
• VGPR rate, defined as the percentage of participants with a 
confirmed Very Good Partial Response (VGPR) or better (i.e., 
VGPR, CR, sCR) 
• Sustained MRD negativity rate: defined as the percentage of 
participants with MRD negativity confirmed by NGS minimum of 
one year apart, per IMWG criteria 
To further evaluate the safety and 
tolerability of belantamab mafodotin when 
administered in combination with bor/dex 
• Changes in safety assessments, including vital signs  
To evaluate self-reported ocular 
symptomatic adverse effects of 
belantamab mafodotin in combination with 
bor/dex 
• Changes from baseline in symptoms and related impacts as 
measured by OSDI 
To further evaluate and compare changes 
in health-related quality of life (HRQOL) 
and symptoms 
• Change from baseline in EQ-5D-3L 
• Change from baseline in PGIS and change in PGIC over time 
To further evaluate the impact of side 
effects on QOL 
• Change from baseline in FACT-GP5 

 
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Objectives 
Endpoints1 
To assess imaging plus MRD-negativity 
rate 
• Imaging plus MRD-negativity rate, defined as the percentage of 
participants who are MRD negative by NGS and who have no 
evidence of disease on PET-CT 
To evaluate and compare healthcare 
resource utilization (HCRU) 
• Number of office/outpatient/hospital clinic visits by specialty 
• Number of emergency room/urgent care facility visits 
• Number and duration of in-patient hospitalizations (total nights, 
including duration by wards [intensive care unit vs. general ward]) 
• Use of supportive care medication 
To further describe the pharmacokinetic of 
belantamab mafodotin when administered 
in combination with bor/dex 
• Derived pharmacokinetic parameter values of belantamab 
mafodotin, and cys-mcMMAF, as data permit 
To explore the exposure-response 
relationship between belantamab 
mafodotin exposure and clinical endpoints 
in participants treated with belantamab 
mafodotin in combination with bor/dex  
• 
Belantamab mafodotin exposure (e.g., concentration, Cmax, or 
AUC) vs. efficacy and safety endpoints (e.g., PFS, ORR, CRR, 
corneal events) 
Explore the relationship between clinical 
response and biologic characteristics 
including, but not limited to, BCMA 
expression on tumor cells and sBCMA 
concentrations  
• 
Assess various biomarkers at baseline and on-treatment, by 
tumor and blood-based analysis of DNA, RNA, and protein 
including but not limited to evaluating baseline BCMA expression 
and/or immune status in tumor tissue and in the tumor 
microenvironment and/or serum soluble BCMA levels, and their 
relationship to clinical response 
1. All categories of disease response (sCR, CR, VGPR, PR, SD, PD) used in the calculation of study endpoints 
will be determined by an IRC using IMWG 2016 criteria. 
ADA = anti-drug antibodies; AE = adverse event; BCMA = B-cell maturation antigen; bor/dex = 
bortezomib/dexamethasone; CBR = Clinical Benefit Rate; CRR = complete response rate; DNA = deoxyribonucleic 
acid; DoR = duration of response; EORTC QLQ C30 = European Organisation for Research and Treatment of 
Cancer Quality of Life Questionnaire 30 item Core module; EORTC IL52 = European Organisation for Research 
and Treatment of Cancer Item Library 52; HCRU = health care resource utilization; HRQoL = health-related quality 
of life; IMWG = International Myeloma Working Group; MRD = minimal residual disease; NGS = Next-generation 
sequencing; ORR = overall response rate; OS = overall survival; PD = progressive disease; PFS = progression-free 
survival; PR = partial response; PRO-CTCAE = Patient Reported Outcomes version of the Common Terminology 
Criteria for Adverse Events; QOL = quality of life; RRMM = relapsed/refractory multiple myeloma; TTR = time to 
response; TTBR = time to best response; TTP = time to progression; VGPR = very good partial response. 
 

 
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4. 
STUDY DESIGN 
4.1. 
Overall Design 
• 
This is a multicenter Phase III, randomized, open-label study evaluating the efficacy 
and safety of the combination of belantamab mafodotin and bor/dex compared with 
the standard of care combination of daratumumab and bor/dex in participants with 
RRMM (Section 6.1).  
• 
The study will include a Screening period, a Treatment period, and a Follow-up 
period.  
• 
During the 28-day Screening period, participants will be evaluated for study 
eligibility per protocol as defined in the Inclusion / Exclusion criteria (Section 5.1 
and Section 5.2). Eligible participants must have a confirmed diagnosis of MM, been 
previously treated with at least 1 prior line of therapy and must have documented 
disease progression during, or following, the most recent line of therapy.  
• 
Following screening, participants will be stratified based on the number of prior 
lines of therapy (1 vs 2/3 vs ≥4), prior bortezomib (yes vs no), and the Revised 
International Staging System (R-ISS I vs II/III), and centrally randomized in a 1:1 
ratio to either arm, as described in Section 6.1. No more than 
% of participants 
with 2 or more prior lines of treatment will be enrolled (including those in Japan 
expansion cohorts). No cross-over will be allowed. 
• 
During the Treatment period, safety and disease assessments will be performed 
regularly according to the Schedule of Activities (Section 1.3) for each arm. 
Treatment will continue in both arms until progressive disease (PD), death, 
unacceptable toxicity, withdrawal of consent or end of study, whichever occurs first. 
Dose interruptions or reductions may be required to address potential drug-
associated toxicities (see Section 6.6) 
• 
For participants who discontinue study treatment for reasons other than PD, disease 
evaluations will continue to be performed every 3 weeks (±3 days) until confirmed 
PD (documented), death, start of a new anti-myeloma treatment, withdrawal of 
consent, loss to follow-up or end of the study (as defined in Section 4.4), whichever 
occurs first. In case of PD, participants will be followed to ascertain subsequent anti-
myeloma therapy, progression on the subsequent line of therapy (PFS2), and 
survival status Q12W (±14 days) until withdrawal of consent, loss to follow-up, 
death or the end of the study. 
• 
GSK may request that updated survival data be collected on all treated/randomized 
participants outside the protocol window noted in the Schedule of Assessments. At 
the time of the request, the site will determine survival status for each participant by 
the method agreed with the participant, unless the participant has withdrawn consent 
for survival follow-up. Where permitted, data from publically available death 
registers will be used for participants withdrawn from study or lost to follow-up 
prior to death. 
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4.2. 
Scientific Rationale for Study Design 
Since their introduction, proteasome inhibitors (PIs) have led to substantial improvements 
in outcomes in MM [Kumar, 2014; Kumar, 2008; Richardson, 2007]. Bortezomib is the 
most frequently used PI approved for the treatment of MM [Velcade USPI, 2021; 
Velcade SmPC, 2020]. Bortezomib is administered in combination with dexamethasone 
as this combination has been shown to improve ORRs in MM [Dimopoulos, 2015; 
Kropff, 2005]. Studies have demonstrated that adding a third agent to bor/dex leads to 
improved patient outcomes, with acceptable safety profiles [Palumbo, 2016; Reeder, 
2009; Richardson, 2010]. European Society for Medical Oncology (ESMO) and National 
Comprehensive Cancer Network (NCCN) guidelines recommend triplet combination 
regimens for induction therapy for fit patients with MM eligible for autologous stem cell 
transplant (ASCT), and triplet combinations are increasingly also preferred for RRMM 
[Moreau, 2017; NCCN, 2018]. 
The addition of the anti-CD38 monoclonal antibody daratumumab to bor/dex has 
demonstrated significant clinical benefit in patients with RRMM. The combination of 
daratumumab and bor/dex resulted in a 68% reduction in the risk of disease progression 
or death (PFS 16.7 vs 7.1 months, HR 0.31, 95% CI: 0.24, 0.39, p<0.001) and a 21% 
increase in ORR (84% vs. 63%, p<0.001) when compared to bor/dex alone [Spencer, 
2018]. The addition of daratumumab to bor/dex was associated with a manageable safety 
profile, with increased rates of neutropenia and thrombocytopenia, and 45% of patients 
had infusion-related reactions [Palumbo, 2016]. Combination therapy with 
daratumumab/bor/dex is approved for the treatment of patients with RRMM and at least 1 
prior line of therapy [see Darzalex USPI, 2019; Darzalex SmPC, 2019] and is a SoC 
regimen in RRMM, and hence an appropriate comparator [Moreau, 2017; NCCN, 2018]. 
Belantamab mafodotin has demonstrated strong single-agent activity in RRMM in a 
FTIH study, with an ORR of 60.0% (95% CI: 42.1, 76.1) and a median PFS of 12.0 
months (95% CI: 3.1, NR) in a heavily pre-treated population (57% ≥5 prior lines of 
therapy) [Trudel, 2018; Trudel, 2019]. Belantamab mafodotin activity in monotherapy 
compares favorably to similar experience with daratumumab monotherapy, where an 
ORR of 29% (95% CI: 20.8, 38.9) and median PFS of 4.0 months (95% CI: 2.8, 5.6) 
were observed in a population with a median of 5 prior lines of therapy [Lonial, 2016].  
In relapsed or refractory multiple myeloma (RRMM), doublet or triplet regimens utilizing 
agents with differing modes of action have dramatically improved outcomes, and are now 
the preferred options at first or subsequent relapses [Moreau, 2017; NCCN, 2018]. As 
described above, multiple studies have demonstrated that adding a third agent, including 
daratumumab, to bor/dex leads to improved patient outcomes with acceptable toxicity 
profiles [Palumbo, 2016; Reeder, 2009; Richardson, 2010].  
Nonclinical data with belantamab mafodotin suggest 
 
 It is therefore 
hypothesized that the combination of belantamab mafodotin and bor/dex will lead to 
greater patient benefit, as measured by progression-free survival (PFS), compared to the 
SoC combination of daratumumab and bor/dex. While there are some potential overlaps 
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in the pattern of identified toxicities between belantamab mafodotin and bor/dex 
(primarily hematologic), they are expected to be manageable.  
The 2-arm design of this study will enable a comparison of the efficacy and safety of 
belantamab mafodotin/bor/dex vs daratumumab/bor/dex in RRMM. The primary 
endpoint is PFS, defined as the time from the date of randomization until the earliest date 
of documented disease progression, determined by a blinded IRC, or death, whichever 
occurs first. Studies have shown a strong correlation between improvements in PFS and 
resultant OS benefits in myeloma, including RRMM [Dimopoulos, 2017; Cartier, 2015]. 
PFS is an acceptable regulatory endpoint with supporting OS data, with the advantages of 
requiring shorter duration of follow-up and not being confounded by subsequent 
treatments. PFS as a primary endpoint has supported registration of several therapies for 
MM including the recent regulatory approvals of carfilzomib and daratumumab 
combination regimens in a similar patient population [Kyprolis SmPC, 2018; Darzalex 
USPI, 2019; Darzalex SmPC, 2019]. 
This study will evaluate a comprehensive panel of secondary endpoints (Section 3) 
including MRD negativity by NGS (key secondary), response rates, and OS (key 
secondary, defined as the time from the date of randomization until the date of death due 
to any cause). 
An IRC consisting of experts within the field will determine disease response to ensure 
consistent and correct application of the IMWG criteria. In order to be able to determine 
disease response, IRC members will receive Central Laboratory disease assessment 
results as well as Electronic Case Report Form (eCRF) data, and Local Laboratory results 
where available. 
An IDMC consisting of at least 2 physicians and 1 statistician, as defined in the IDMC 
Charter, will review data from the interim analysis. An interim analysis is planned based 
on 
, allowing for early stopping due to efficacy. In addition, safety 
data will be reviewed periodically starting from when 
 
 and then every 
 or as requested by the IDMC thereafter. 
Ad hoc meetings may be convened at the discretion of the IDMC or if requested by the 
sponsor. Additional details will be provided in the IDMC Charter. 
4.3. 
Justification for Dose 
4.3.1. 
Belantamab Mafodotin Dose 
The belantamab mafodotin monotherapy dose in RRMM has been chosen to be 
2.5 mg/kg when administered on a Q3W schedule. This is based on the results from 
Study 205678 that evaluated 2 doses of belantamab mafodotin (2.5 mg/kg and 3.4 mg/kg) 
administered Q3W until disease progression in participants who have failed at least 
3 prior lines of anti-myeloma therapy, including an anti-CD38 antibody, and who are 
refractory to an IMiD and a proteasome inhibitor (n=218). Belantamab mafodotin 
monotherapy has generally been well tolerated, with manageable toxicities [Lonial, 
2020]. The most frequent AEs (≥30% of participants) were corneal exam findings, cough, 
increased AST, thrombocytopenia/decreased platelet count, nausea, anemia, diarrhea, 
pyrexia, and chills (Section 2.2.4).  
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Belantamab mafodotin dose of 2.5 mg/kg Q3W is currently being evaluated in 
combination with bortezomib and dexamethasone in Study 207497 in RRMM 
participants who have failed at least 1 prior line of therapy. 
 
 
 
, this combination dose has 
been shown to have an acceptable safety profile, with an adverse event profile consistent 
with each of the adverse event profiles for bortezomib, dexamethasone, and belantamab 
mafodotin monotherapy.  
The pharmacokinetics of belantamab mafodotin were evaluated in combination with 
bortezomib and dexamethasone. 
 
 
 
Based on this information, a dose of 2.5 mg/kg of belantamab mafodotin in combination 
with bortezomib and dexamethasone is planned for this study. 
4.3.2. 
Daratumumab Dose 
Daratumumab is an anti-CD38 monoclonal antibody approved in the US, EU and a 
number of other countries worldwide for the treatment of RRMM as both a mono- and 
combination therapy [Darzalex USPI, 2019; Darzalex SmPC, 2019].  
Daratumumab will be administered at the approved dose for treatment as a combination 
therapy with bor/dex (refer to the most recently approved country-specific IV 
daratumumab label). For participants assigned to Treatment Arm B, daratumumab will be 
administered as an IV infusion at a dose of 16 mg/kg weekly for Cycles 1-3 (Weeks 1-9), 
then once every 3 weeks (Q3W) on Day 1 of Cycles 4-8 (Weeks 10-24), and every 4 
weeks thereafter (C9+, Week 25 onwards). For the first daratumumab dosing in Week 1 
only, in accordance with the local/regional label and institutional guidance and to 
facilitate administration, the single infusion on Day 1 may be split over 2 days (see 
Section 6.1.4 for details). Each participant’s dose will be calculated based on the 
participant’s weight to the nearest kilogram. For each daratumumab infusion, participants 
will receive pre-infusion and post-infusion medications to reduce the risk of infusion-
related reactions as specified in Section 6.1.4.1. 
4.3.3. 
Bortezomib Dose 
Bortezomib is a proteasome inhibitor approved for use in patients with MM. In both 
treatment arms, bortezomib will be administered at the approved dose regimen for use in 
combination with dexamethasone, according to the most recently approved 
country-specific bortezomib label . This is also the approved regimen for use in 
combination therapy with daratumumab/bor/dex (refer to the most recently approved 
country-specific IV daratumumab label). 
Bortezomib will be administered at 1.3 mg/m2 SC on Days 1, 4, 8, and 11 of every 
21-day cycle for a total of 8 cycles, according to the most recently approved 
country-specific bortezomib label. 
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At least 72 hours/3 calendar days should elapse between consecutive doses of 
bortezomib. 
4.3.4. 
Dexamethasone Dose 
Dexamethasone [Dexamethasone USPI, 2018; Dexamethasone SmPC, 2018] will be 
administered according to the regimen approved for use in combination with bortezomib, 
according to the most recently approved country-specific bortezomib label.  
Dexamethasone will be administered at 20 mg, orally or IV, on Days 1, 2, 4, 5, 8, 9, 11, 
and 12 of every 21-day cycle for the first 8 cycles.  
Starting dose of dexamethasone may be reduced to 10 mg for participants older than 
75 years of age, who have a body-mass index of less than 18.5, who had previous 
unacceptable side effects associated with glucocorticoid therapy, or who are unable to 
tolerate the starting dose (For guidance on further dose modification, see Table 15 in 
Section 6.6.4). 
Dexamethasone should be taken at the same time of the day and may be taken at home. 
Bortezomib plus dexamethasone will be administered according to institutional 
instructions. 
4.4. 
End of Study Definition 
A participant is considered to have completed the study if he or she is followed until 
death or the end of study. 
End of study is defined as 5 years from Last Participant First Visit (LSFV) for 
participants enrolled into the global study, or when all participants enrolled into the 
global study have died, withdrawn consent, or have been lost to follow-up, whichever 
occurs first. At this time no further participant data will be collected. 

 
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5. 
STUDY POPULATION 
The study will enroll adult participants with RRMM who have been previously treated 
with at least 1 prior line of therapy, and who have documented disease progression 
during, or after, their most recent therapy. No more than
% of participants with 2 or 
more prior lines of treatment will be enrolled (including those in Japan expansion 
cohorts). Full criteria are included below. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria are 
met: 
1. Capable of giving signed informed consent as described in Section 10.1.3, which 
includes compliance with the requirements and restrictions listed in the informed 
consent form (ICF) and in this protocol. 
2. Male or female, 18 years or older (at the time consent is obtained). 
3. Confirmed diagnosis of multiple myeloma as defined by the IMWG criteria 
[Rajkumar, 2014]. 
4. Previously treated with at least 1 prior line of MM therapy, and must have 
documented disease progression during or after their most recent therapy. Note: 
induction + ASCT + maintenance is 1 line of therapy 
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (Section 
10.6). 
6. Participants with a history of autologous SCT are eligible for study participation 
provided the following eligibility criteria are met: 
a. ASCT was >100 days prior to initiating study treatment, and 
b. No active bacterial, viral, or fungal infection(s) present. 
7. Must have at least ONE aspect of measurable disease, defined as one the following:  
a. Urine M-protein excretion ≥200 mg/24h, or 
b. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or 
c. Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) 
and an abnormal serum free light chain ratio (<0.26 or >1.65). 
8. All prior treatment-related toxicities (defined by National Cancer Institute Common 
Toxicity Criteria for Adverse Events [NCI-CTCAE] v5.0) must be ≤ Grade 1 at the 
time of enrollment, except for alopecia.  
9. Adequate organ system functions as defined by the laboratory assessments listed in 
Table 6. 
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Table 6 
Adequate Organ System Function Based on Safety Assessments 
Organ System and Laboratory Tests 
Laboratory Values 
Hematologic 
Absolute neutrophil count (ANC)a 
1.0 × 109/L 
Hemoglobin 
8.0 g/dL 
Platelets 
75x109/L 
Hepatic 
Total bilirubin 
≤1.5xULN; (Isolated bilirubin >1.5xULN is acceptable if bilirubin is 
fractionated and direct bilirubin is <35%) 
Alanine aminotransferase (ALT) 
2.5xULN 
Renal 
eGFRb 
30 mL/min/1.73 m2  
Urine dipstick for protein 
 
OR 
 
Albumin/creatinine ratio (from spot 
urine) 
Negative/trace [if ≥1+, only eligible if confirmed ≤500 mg/g 
(56 mg/mmol) by albumin/creatinine ratio (spot urine from first void)] 
 
 
≤500 mg/g (56 mg/mmol) 
NOTE:  Laboratory results obtained during Screening should be used to determine eligibility criteria. In situations 
where laboratory results are outside the permitted range, the investigator may re-test the participant and the 
subsequent within range screening result may be used to confirm eligibility. 
a. 
Without growth factor support, blood transfusion or platelet stimulating agents for the past 14 days, excluding 
erythropoietin. 
b. 
As calculated by Modified Diet in Renal Disease (MDRD) formula (Section 10.7). 
 
10. Female Participants: 
Contraceptive use by women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies. 
A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least 1 of the following conditions applies: 
Is not a woman of childbearing potential (WOCBP) 
OR 
Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), preferably with low user dependency (Section 10.3) during the 
intervention period and for 4 months after the last dose of belantamab mafodotin, 
3 months from the last dose of daratumumab, and 7 months from the last dose of 
bortezomib, whichever is longer, and agrees not to donate eggs (ova, oocytes) for the 
purpose of reproduction during this period. The investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of study 
intervention. 
WOCBP must have a negative highly sensitive serum pregnancy test within 72 hours 
of dosing on C1D1.  
Additional requirements for pregnancy testing during and after study intervention are 
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The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
11. Male Participants: 
Contraceptive use by men should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies.  
Male participants are eligible to participate if they agree to the following from the 
time of first dose of study until 6 months after the last dose of belantamab mafodotin, 
and 4 months from the last dose of bortezomib, to allow for clearance of any altered 
sperm:  
Refrain from donating sperm 
PLUS either: 
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long term and persistent basis) and agree to remain abstinent  
OR 
Must agree to use contraception/barrier as detailed below: 
Agree to use a male condom, even if they have undergone a successful vasectomy 
and female partner to use an additional highly effective contraceptive method with a 
failure rate of <1% per year as described in Section 10.3 when having sexual 
intercourse with a WOCBP (including pregnant females). 
5.2. 
Exclusion Criteria 
A participant will not be eligible for inclusion in this study if any of the following criteria 
are met: 
1. Intolerant to daratumumab. 
2. Refractory to daratumumab or any other anti-CD38 therapy (defined as progressive 
disease during treatment with anti-CD38 therapy, or within 60 days of completing 
that treatment). 
3. Intolerant to bortezomib, or refractory to bortezomib (defined as progressive disease 
during treatment with a bortezomib-containing regimen of 1.3 mg/m2 twice weekly, 
or within 60 days of completing that treatment). Note:  participants with progressive 
disease during treatment with a weekly bortezomib regimen are allowed. 
4. Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain. 
5. Prior treatment with anti-BCMA therapy. 
6. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose 
of study drugs, or treatment with an investigational agent or approved systemic anti-
myeloma therapy (including systemic steroids) within 14 days or 5 half-lives of 
receiving the first dose of study drugs, whichever is shorter. 
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8. Has received radiotherapy to a large pelvic area (check with sponsor). Bridging 
radiotherapy otherwise is allowed. NOTE: Disease assessment should be repeated if 
RT is done prior to first dose of study drug within screening window. 
9. Prior allogenic stem cell transplant. NOTE – Participants who have undergone 
syngeneic transplant will be allowed, only if no history of GvHD. 
10. Any major surgery within 4 weeks prior to the first dose of study drug. Exception 
allowed for bone stabilizing surgery after consultation with medical monitor. 
11. Presence of active renal condition (infection, requirement for dialysis or any other 
condition that could affect participant’s safety). Participants with isolated proteinuria 
resulting from MM are eligible, provided they fulfil criteria given in Table 6. 
12. Any serious and/or unstable pre-existing medical, psychiatric disorder or other 
conditions (including lab abnormalities) that could interfere with participant’s safety, 
obtaining informed consent or compliance to the study procedures.  
13. Evidence of active mucosal or internal bleeding. 
14. Cirrhosis or current unstable liver or biliary disease per investigator assessment 
defined by the presence of ascites, encephalopathy, coagulopathy, 
hypoalbuminaemia, esophageal or gastric varices, persistent jaundice. NOTE: Stable 
non-cirrhotic chronic liver disease (including Gilbert’s syndrome or asymptomatic 
gallstones) is acceptable if participant otherwise meets entry criteria. 
15. Previous or concurrent malignancies other than multiple myeloma, unless the second 
malignancy has been considered medically stable for at least 2 years. The participant 
must not be receiving active therapy, other than hormonal therapy for this disease. 
NOTE: Participants with curatively treated non-melanoma skin cancer are allowed 
without a 2-year restriction. 
16. Evidence of cardiovascular risk including any of the following: 
a. 
Evidence of current clinically significant untreated arrhythmias, including 
clinically significant ECG abnormalities including second degree (Mobitz Type 
II) or third degree atrioventricular (AV) block. 
b. History of myocardial infarction, acute coronary syndromes (including unstable 
angina), coronary angioplasty, or stenting or bypass grafting within 3 months of 
Screening. 
c. 
Class III or IV heart failure as defined by the New York Heart Association 
functional classification system (Section 10.8).  
d. Uncontrolled hypertension. 
17. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to 
drugs chemically related to belantamab mafodotin, daratumumab, bortezomib, boron 
or mannitol or any other components of the study treatment. 
18. Active infection requiring treatment. 
19. Known HIV infection,  unless the participant can meet all of the following criteria: 
• Established anti-retroviral therapy (ART) for at least 4 weeks and HIV viral 
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• CD4+ T-cell (CD4+) counts ≥350 cells/L  
• No history of AIDS-defining opportunistic infections within the last 12 
months  
Note: consideration must be given to ART and prophylactic antimicrobials that may have 
a drug-drug interaction and/or overlapping toxicities with belantamab mafodotin or other 
combination products as relevant (see Section 6.5.2). 
20. Patients with Hepatitis B will be excluded unless the following criteria can be met. 
Serology 
Screening 
During Study Treatment 
HBcAb+, HbsAg- 
• HBV DNA undetectable 
• Monitoring per protocol 
(Table 18) 
• Antiviral treatment 
instituted if HBV DNA 
becomes detectable 
HBsAg+ at screen 
or within 3 months 
prior to first dose  
• HBV DNA undetectable 
• Highly effective antiviral treatment 
started at least 4 weeks prior to first 
dose of study treatment 
• Baseline imaging per protocol 
• Participants with cirrhosis are 
excluded 
• Antiviral treatment 
maintained throughout 
study treatment 
• Monitoring and 
management per protocol 
(Table 18) 
 
NOTE: presence of Hep B surface antibody (HBsAb) indicating previous vaccination 
will not exclude a participant. 
21. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at 
screening or within 3 months prior to first dose of study treatment unless the 
participant can meet the following criteria: 
• RNA test negative 
• Successful anti-viral treatment (usually 8 weeks duration) is required, 
followed by a negative HCV RNA test after a washout period of at least 4 
weeks. 
22. Current corneal epithelial disease except for mild punctate keratopathy (Section 10.9). 
23. Intolerance or contraindications to anti-viral prophylaxis. 
24. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, organomegaly, 
endocrinopathy, monoclonal plasma proliferative disorder, skin changes) or active 
plasma cell leukaemia at the time of screening. 
 
5.3. 
Lifestyle Considerations 
Contact lenses are prohibited for participants on Treatment Arm A (belantamab 
mafodotin/bor/dex) while on the study treatment (from first dose to EoT). Contact lens 

 
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use may be restarted after EoT after a qualified eye care specialist (Appendix 10) 
confirms there are no other contraindications. No other lifestyle restrictions are required 
for participants in this study. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized. 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 events 
(SAEs). 
Individuals identified as Screen Failures may be rescreened if the failure was based on 
elements of eligibility that may change, e.g., laboratory test results. Rescreening of a 
participant more than once requires discussion with the Medical Monitor. Rescreened 
participants must be assigned a new unique participant number that is different from the 
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6. 
STUDY INTERVENTION 
6.1. 
Study Intervention(s) Administered 
Refer to the Pharmacy Manual for further details on preparation, handling, and 
administration instructions for study interventions. A summary of the identity and 
characteristics of the individual components of the Study Treatment is shown in Table 7. 
Table 7 
Study Treatment 
Product name 
 Belantamab 
mafodotin 
Bortezomib 
Daratumumab 
Dexamethasone 
Dosage form 
Lyophilized 
powder for 
reconstitution 
Lyophilized 
powder for 
reconstitution 
Concentrate for solution 
for IV infusion  
Tablet/ solution for IV 
infusion. 
Dosage level(s): 
2.5 mg/kg 
1.3 mg/m2 
16 mg/kg IV 
 
(Split dosing (2 x 
8 mg/kg IV) is only a 
possibility in W1) 
20 mg oral or IV  
Route of 
Administration 
Intravenous 
infusion – 30 
min- 60 min 
Subcutaneous 
Intravenous 
Oral or Intravenous (has 
to be IV before first dose 
of daratumumab in 
Treatment Arm B) 
Frequency of 
Administration 
Single dose: 
 
IV infusion on 
Day 1 of each 
21-day cycle 
Cycle 1 – 8: 
Once daily on 
Days 1, 4, 8 and 
11 of each 21-
day cycle 
Cycle 1 – 3: Once 
weekly of each 21-day 
cycle (Except split 
dosing possibility in W1) 
 
Cycle 4 – 8: Once every 
3 weeks on Day 1 of 
each 21-day cycle 
 
Cycle 9 onward: Once 
every 4 weeks on day 1 
of each 28-day cycle 
Cycle 1 – 8: Once daily 
on Days 1, 2, 4, 5, 8, 9, 
11, and 12 of each 21-day 
cycle 
Use 
Investigational 
Product 
Arm A – 
Investigational 
Product 
 
Arm B - 
Comparator 
Comparator 
Arm A – Investigational 
Product 
 
Arm B - Comparator 
Non-IMP  
(Japan only) 
Not 
Applicable 
Background 
Treatment 
Standard of Care 
Background Treatment 
Authorized 
AxMP/Unauthorized 
AxMP (EU only) 
Not 
Applicable 
Authorized 
AxMP – 
Background 
Treatment 
Authorized AxMP – 
Standard of Care 
Authorized AxMP – 
Background Treatment 
 

 
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6.1.1. 
Treatment Arm A Dosing Schedule 
The dosing schedule for Treatment Arm A (belantamab mafodotin in combination with 
bor/dex) is depicted in Figure 2. 
Figure 2 
Summary of Dosing Schedule for Treatment Arm A (Belantamab 
mafodotin/bor/dex) 
 
Belantamab mafodotin will be administered intravenously (IV) at the recommended 
combination dose of 2.5 mg/kg on Day 1 (D1) of every 21-day cycle until confirmed PD, 
unacceptable toxicity, death, withdrawal of consent or study end, whichever occurs first. 
A window of ±3 days is acceptable for administration belantamab mafodotin after C1D1, 
but at least 21 days should elapse between consecutive planned doses of belantamab 
mafodotin. Ocular prophylaxis is required throughout treatment (Section 6.1.3.2). 
Bortezomib 1.3 mg/m2 will be administered subcutaneously (SC) on Days 1, 4, 8, and 11 
of every 21-day cycle for a total of 8 cycles. Bortezomib should be administered 
approximately 1 hour after the belantamab mafodotin infusion is complete, assuming the 
participant is clinically stable. 
Dexamethasone 20 mg (PO or IV) should be administered on the day of and the day 
after bortezomib treatment. For participants with contraindications or intolerance to this 
dose, refer to Section 6.6.4. On days where bortezomib and dexamethasone 
administration coincides with administration of belantamab mafodotin, dexamethasone 
should be administered PO or IV prior to the infusion of belantamab mafodotin. 
Efficacy assessments will be performed every 3 weeks (±3 days), irrespective of dosing. 
See Section 6.6 for guidance on dose modification and dose delays. 
For details on Home Healthcare and Telemedicine Approaches, please refer to Appendix 
15. 
6.1.2. 
Treatment Arm B Dosing Schedule 
The dosing schedule for Treatment Arm B (daratumumab in combination with bor/dex) is 
depicted in Figure 3. 

 
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Figure 3 
Summary of Dosing Schedule for Treatment Arm B 
(Daratumumab/bor/dex) 
  
* Corticosteroid is required as pre- and post-medication on the days when daratumumab is administered without 
bor/dex, as detailed in Section 6.1.4.1. 
 
Daratumumab 16 mg/kg IV will be administered according to the approved label 
schedule in combination with bor/dex weekly for Cycles 1 through 3 (Weeks 1 to 9) (21-
day cycles, total of 9 doses), on Day 1 of Cycles 4 thorough 8 (Weeks 10 to 24) (21-day 
cycles, total of 5 doses), and then every 4 weeks from Cycle 9 (Week 25) onwards (28-
day cycles). For the first dose of daratumumab dosing at Week 1 only, in accordance with 
the label and institutional guidance and to facilitate administration, the single infusion of 
daratumumab may be split over 2 days (see Section 6.1.4 and the most recently approved 
country-specific IV daratumumab label). 
Bortezomib 1.3 mg/m2 will be administered SC on Days 1, 4, 8, and 11 of every 21-day 
cycle for a total of 8 cycles. Bortezomib should be administered approximately 1 hour 
after the daratumumab infusion is complete, assuming the participant is clinically stable. 
Dexamethasone 20 mg (PO or IV) should be administered on the day of and the day 
after bortezomib treatment. Administration should be IV prior to the first dose of 
daratumumab. Starting dose of dexamethasone may be reduced to 10 mg for participants 
older than 75 years of age, who have a body-mass index of less than 18.5, who had 
previous unacceptable side effects associated with glucocorticoid therapy, or who are 
unable to tolerate the starting dose (For guidance on further dose modification, see Table 
15, Section 6.6.4). On days where bortezomib and dexamethasone administration 
coincides with administration of daratumumab, dexamethasone should be administered 
prior to the IV infusion of daratumumab. Corticosteroids are required as part of pre/post-
medication for daratumumab infusions (Section 6.1.4.1). 
Efficacy assessments will be performed every 3 weeks (±3 days), irrespective of dosing. 
See Section 6.6 for guidance on dose modification and dose delays. 
For details on Home Healthcare and Telemedicine Approaches, please refer to Appendix 
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6.1.3. 
Belantamab Mafodotin 
Belantamab mafodotin 2.5 mg/kg (Table 8) will be administered intravenously. See the 
Pharmacy Manual for further guidance on administration. The dose to be administered is 
based on actual body weight measurement on C1D1 prior to dosing. For subsequent 
dosing, if the change in body weight is 10% from C1D1 (prior to dosing), the dose does 
not need to be recalculated. However, if the change of body weight is >10%, the dose 
should be re-calculated based on the actual body weight at the time of dosing. The dose 
may be reduced to address toxicity according to protocol guidelines (Section 6.6). 
Table 8 
Administration of Belantamab Mafodotin 
Product name 
Belantamab Mafodotin  
Dosage form 
Powder for solution for infusion 
Unit dose strength(s)/dose 
level(s) 
100 mg / 2.5 mg/kg 
Route/Administration/Duration 
Intravenous use (see Pharmacy Manual)   
Dosing instructions 
Reconstitute belantamab mafodotin for injection, 100 mg with 2.0 mL of sterile 
water for injection, dilute with saline before use.  
Dilute belantamab mafodotin in normal 0.9% saline to the appropriate 
concentration for the dose [See the GSK document No. RPS-CLIN-105644]. 
Doses of belantamab mafodotin are to be administrated as an IV infusion via an 
infusion pump. See the Investigator’s Brochure for compatible administration 
materials. 
 
6.1.3.1. 
Belantamab Mafodotin Pre/Post-medication 
Premedication is not required prior to infusion unless deemed medically appropriate by 
the investigator. Premedication should be considered in any participant who experienced 
an IRRs at first or any subsequent infusion with belantamab mafodotin. 
On days where belantamab mafodotin administration coincides with bortezomib, 
dexamethasone may be administered IV or PO prior to belantamab mafodotin 
administration.  
IRRs should be managed by guidelines provided in Section 7.1.4. A participant that 
experiences a Grade 4 IRR associated with belantamab mafodotin should be permanently 
withdrawn from the study. 
6.1.3.2. 
Corneal Supportive Care Guidelines 
Corneal events, which commonly manifest as superficial microcystic keratopathy, have 
been observed with ADCs, including those conjugated to MMAF. 

 
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Further information regarding corneal events associated with belantamab mafodotin, 
including prophylactic measures are in Section 10.9. See the SoA (Section 1.3) for 
guidance on required monitoring for corneal toxicity. 
Sites are required to establish a close collaboration with a qualified eye care specialist 
(Appendix 10) who will be responsible for assessing participants on Treatment Arm A, in 
close communication with GSK Medical Monitor and possibly a GSK ophthalmologist, 
and managing those who develop corneal toxicity. 
Participants on Treatment Arm A will be assessed by a qualified eye care specialist 
(Appendix 10) at screening/ baseline, and then Q3W prior to dosing up to the sixth dose 
of belantamab mafodotin (assessment window of up to 5 days prior to dosing, but all 
effort should be made to schedule as close to belantamab mafodotin dosing as possible), 
as detailed in the SoA. If there are no significant ocular examinations findings, patient’s 
symptoms or vision changes at or prior to the time of the sixth dose exam, participants 
may have their ophthalmologic exams decreased to once every 3 months. If a participant 
subsequently develops vision changes or other ocular symptoms, the participant should 
be promptly evaluated by a qualified eye care specialist. In case of persistent ophthalmic 
exam findings, newly developed ocular symptoms or vision changes at the sixth dose 
exam, the participants will have further ophthalmologic exams, at least every cycle until 
resolution (to Grade 1 or baseline) or more frequently as clinically indicated by the 
qualified eye care specialist. 
If steroid eye drops are deemed medically necessary and prescribed, intraocular pressure 
must be monitored if used for >7 days. 
Participants who have treatment-related ocular AEs present at the end of treatment will 
continue to be followed by qualified eye care specialist at least every 3 months for up to 
12 months or until resolution (to Grade 1 or baseline), whichever comes first. 
Treatment related corneal events are to be graded according to the guidelines of the 
Keratopathy Visual Acuity (KVA) Scale (Appendix 9, Table 30). Dose modification 
guidelines and stopping criteria for belantamab mafodotin treatment-related corneal 
events based on KVA scale are provided in Table 11.  
6.1.3.3. 
Ocular Prophylaxis for Treatment Arm A 
Ocular prophylaxis should be instituted for all participants on Treatment Arm A as 
detailed in the SoA. Ocular prophylaxis includes: 
• Prophylactic preservative-free artificial tears must be administered in each eye at 
least 4-8 times daily, beginning on Cycle 1 Day 1 until the end of belantamab 
mafodotin treatment. 
• At the start of each belantamab mafodotin infusion, participants may apply 
cooling eye masks to their eyes for as long as tolerated, up to 4 hours.  

 
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6.1.4. 
Daratumumab 
Daratumumab 16 mg/kg should be administered as an intravenous infusion after dilution 
in 0.9% sodium chloride. The dose to be administered is based on actual body weight 
measurement on C1D1 prior to dosing. For subsequent dosing, if the change in body 
weight is 10% from C1D1 (prior to dosing), the dose does not need to be recalculated. 
However, if the change of body weight is >10% from C1D1 (prior to dosing), the dose 
should be re-calculated based on the actual body weight at the time of dosing. 
Administer daratumumab intravenously at the infusion rate described in the local label. 
Consider incremental escalation of the infusion rate only in the absence of infusion 
reactions. 
For the first daratumumab dosing at Week 1 only, in accordance with the local/regional 
label and institutional guidance and to facilitate administration, the single infusion of 16 
mg/kg can be split into 2 infusions of 8 mg/kg administered on consecutive days (Day 1 
and Day 2, see Table 2 and Section 6.1.4.1 below). If the Day 2 dose cannot be 
administered, it will not be made up. See the Pharmacy Manual and the most recently 
approved country-specific IV daratumumab label.  
6.1.4.1. 
Daratumumab Required Pre/Post-medication 
The administration of pre- and post-infusion medications to reduce the risk of IRRs for 
daratumumab should follow the guidance reported in the most recently approved country-
specific IV daratumumab label. 
6.1.4.2. 
Antiviral Prophylaxis 
Antiviral prophylaxis is recommended in accordance with local prescribing information 
in participants being treated with bortezomib or daratumumab. 
6.1.4.3. 
Interference with Serological Testing 
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect 
antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect 
antiglobulin test may persist for up to 6 months after the last daratumumab infusion. 
Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the 
participant’s serum. The determination of a participant’s ABO and Rh blood type are not 
impacted [Darzalex USPI, 2019; Darzalex SmPC, 2019].  
Notify blood transfusion centers of this interference with serological testing and inform 
blood banks that a participant has received daratumumab.  
As specified in Table 19, participants on Treatment Arm B should undergo blood typing and 
screening prior to starting daratumumab, and should carry a card with their blood antigen 
profile with them at all times. 

 
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6.1.4.4. 
Interference with Serum Protein Electrophoresis and Immunofixation 
Tests 
Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both 
the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the 
clinical monitoring of endogenous M-protein. This interference can impact the 
determination of complete response and of disease progression in some participants with 
IgG kappa myeloma protein [Darzalex USPI, 2019; Darzalex SmPC, 2019].  
Participants on Treatment Arm B with IgG Kappa MM are required to undergo further 
testing with a daratumumab-specific IFE assay (Section 1.3 and Section 8.1.2) in the 
following settings:  
• VGPR with suspected CR 
• CR with suspicion of PD (e.g increases in monoclonal protein as measured by 
SPEP that may or may not yet meet criteria for PD). 
6.1.5. 
Bortezomib 
Bortezomib 1.3 mg/m2 SC will be administered on Days 1, 4, 8, and 11 of every 21-day 
cycle for a total of 8 cycles. Bortezomib should be administered approximately 1 hour 
after the belantamab mafodotin or daratumumab infusion is complete, assuming the 
participant is clinically stable. In participants who experience an IRR during or after 
belantamab mafodotin or daratumumab administration, the administration of bortezomib 
will be delayed until the IRR has resolved and the participant is considered clinically 
stable.  
Bortezomib dosing is based on the participant’s body surface area (BSA), which is 
calculated using a nomogram [e.g.,West, 2000]. The reconstituted concentration of 
bortezomib for subcutaneous administration (2.5 mg/mL) is greater than the reconstituted 
concentration of bortezomib for intravenous administration (1 mg/mL). Because each 
route of administration has a different reconstituted concentration, caution should be used 
when calculating the volume to be administered.  
Dose modifications may be required for safety. Refer to Section 6.6.3 for more 
information. 
At least 72 hours/3 calendar days should elapse between consecutive doses of 
bortezomib.  
Sites for each injection should be rotated. New injections should be given at least 1 inch 
from an old site and never into areas where the site is tender, bruised, erythematous, or 
indurated. 
If local injection site reactions occur following administration of bortezomib SC, a less 
concentrated solution (1 mg/mL instead of 2.5 mg/mL) may be administered SC. 
Refer to the Pharmacy Manual for further details on preparation, handling, and 
administration contained in package inserts. 

 
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6.1.5.1. 
Dose Calculation 
After determining the participant’s BSA in m2, use the following equations to calculate 
the total volume (mL) of reconstituted bortezomib to be administered: 
For subcutaneous administration (2.5 mg/mL concentration): 
[bortezomib dose (mg/m2) × participant BSA (m2)] ÷ [2.5 mg⁄mL] = Total 
bortezomib volume (mL) to be administered 
6.1.5.2. 
Drug Interactions 
For details on concomitant medications that can alter bortezomib exposure see Section 
6.5.2. 
6.1.6. 
Dexamethasone 
Dexamethasone 20 mg PO or IV will be given on day of and day after bortezomib 
administration (Days 1, 2, 4, 5, 8, 9, 11, and 12) of every 21-day cycle for the first 8 
cycles. The dexamethasone starting dose may be reduced at PIs discretion as described in 
Table 15, Section 6.6.4. Dexamethasone should be taken at the same time of the day and 
may be taken at home when administered PO. 
Refer to the Pharmacy Manual and package inserts for further details on preparation, 
handling, and administration. 
6.2. 
Preparation/Handling/Storage/Accountability 
• The investigator or designee must confirm appropriate temperature conditions 
have been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
• Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions 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. 
• The investigator, institution, or the head of the medical institution (where 
applicable) is responsible for study intervention accountability, reconciliation, and 
record maintenance (i.e., receipt, reconciliation, and final disposition records). 
• Further guidance and information for the final disposition of unused study 
intervention are provided in the Study Reference Manual. 
• Precaution will be taken to avoid direct contact with the study interventions. A 
Material Safety Data Sheet (MSDS) describing occupational hazards and 
recommended handling precautions will be provided to the investigator. In the 
case of unintentional occupational exposure notify the Medical Monitor and/or 
GSK study contact. 

 
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6.3. 
Measures to Minimize Bias: Randomization and Blinding 
Open-label using 
central 
randomization 
via Interactive 
Response 
Technology (IRT) 
system 
This is an open-label study; therefore, no blinding of treatment 
identity is needed for either Treatment Arm A or Treatment Arm 
B. However, to ensure trial integrity steps will be taken to restrict 
access to key information while the study is ongoing and prevent 
data aggregation except for where specified in the protocol. 
Upon completion of all the required screening assessments, 
eligible participants will be centrally randomized using a central 
Interactive Response Technology (IRT) system, RAMOS NG, by 
the investigator or authorized site staff. RAMOS NG allows 
study sites to register and randomize participants, and also 
records stratification information.  
Randomization list will be done centrally using a randomization 
schedule generated by the GSK Clinical Statistics Department in 
RandALL NG, which will assign participants in a 1:1 ratio to 
Treatment Arm A and Treatment Arm B. Separate randomization 
lists will be generated for any extension cohorts required.  
Stratification 
Stratification factors used for the stratified analyses are number 
of prior lines of therapy (1 vs 2 or 3 vs ≥4), prior bortezomib (yes 
vs no) and Revised International Staging System (R-ISS I vs 
II/III). 
No more than
% of participants with 2 or more prior lines of 
treatment will be enrolled. No cross-over will be allowed. 
 
6.4. 
Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention directly from 
the investigator or designee, under medical supervision. The date and time of each dose 
administered in the clinic will be recorded in the source documents. The dose of study 
intervention and study participant identification will be confirmed at the time of dosing 
by a member of the study site staff other than the person administering the study 
intervention.  
Belantamab mafodotin and daratumumab will be intravenously administered to 
participants at the site. Bortezomib will be subcutaneously administered to participants at 
the site. Administration will be documented in the source documents and reported in the 
case report form (eCRF). 
When participants self-administer oral study treatment(s) at home, dosing with 
dexamethasone will be recorded in the Participant’s Study Medication Diary. The entries 
in the Diary will be assessed through querying the participant during the site visits and 
documented in the source documents and eCRF. A record of the number of doses 
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dispensed to and taken by each participant must be maintained and reconciled with study 
treatment and compliance records. Treatment start and stop dates, including dates for 
treatment delays and/or dose reductions will also be recorded in the eCRF. 
6.5. 
Concomitant Therapy 
Participants will be instructed to inform the investigator prior to starting any new 
medications from the time of first dose of study treatment until the EoT Visit. 
Concomitant medications administered after the EoT should be recorded for SAEs/AESIs 
as defined in Section 8.3. Any concomitant medication (including over-the-counter or 
prescription medicines, vitamins, and/or herbal supplements) that the participant is 
receiving at the time of enrollment or receives during the study must be recorded along 
with: 
• reason for use 
• dates of administration including start and end dates 
• dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant therapy. 
6.5.1. 
Permitted Concomitant Therapies 
Participants should receive full supportive care during the study, including transfusions of 
blood products, growth factors, and treatment with antibiotics, anti-emetics, 
antidiarrheals, and analgesics, as appropriate. Concomitant therapy with bisphosphonates 
is allowed and recommended. See Section 6.1.4.1 for recommended concomitant 
therapies to be used with daratumumab. 
Participants may receive local irradiation for pain or stability control. 
Use of approved monoclonal antibody treatments for serious conditions unrelated to 
multiple myeloma, such as pre-exposure prophylaxis of COVID-19, may be permitted, 
but needs to be discussed with the GSK Medical Monitor. 
While on study, a participant who is diagnosed with an unrelated malignancy that can be 
addressed by local therapy can remain on study, study treatment may be resumed as per 
investigator discretion after discussion with the GSK Medical Monitor.  The participant 
should continue to be followed for disease progression of multiple myeloma as per the 
SoA. 
6.5.2. 
Prohibited Concomitant Therapies 
Chronic treatment with oral steroids other than treatment specified in the SoA are 
prohibited, with the following exceptions: 
• Low dose prednisolone (≤10 mg/day) as substitution in participants with adrenal 
insufficiency.  
• Short course (7 days) of steroids to manage an adverse event.  

 
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• Steroids to treat IRRs.  
• Inhaled, intranasal, topical and topical ophthalmic steroids. 
Administration of live or live-attenuated vaccines are contraindicated 30 days prior to the 
first dose of study treatment and while receiving study treatment. Use of live or live-
attenuated vaccines is further contraindicated for at least 70 days following the last dose 
of belantamab mafodotin. Killed or inactivated vaccines may be administered; however, 
the response to such vaccines cannot be predicted. 
Other prohibited therapies include: 
• Plasmapheresis: prohibited from 7 days prior to first dose through the end of 
study.  
• Any other approved or investigational anti-myeloma therapy not specified in this 
protocol (including but not limited to immunomodulatory and antineoplastic 
drugs or proteasome inhibitors).  This is inclusive of all medications with activity 
against multiple myeloma and medications used for other indications that have 
anti-myeloma properties.  
• Investigational agents other than belantamab mafodotin 
• Inhibitors of P-gp and Organic Anion Transporting Polypeptide (OATP):  Caution 
should be exercised when belantamab mafodotin is combined with strong 
inhibitors of P-gp. Strong inhibitors of OATP should be avoided unless 
considered medically necessary.  
• See the SRM for more detailed information and a list of Prohibited Concomitant 
Medications. 
For participants receiving anti-HIV and anti-microbials: 
Anti-HIV and anti-microbials that are OATP inhibitors (list provided below; list covering 
other classes of drugs) and thus prohibited unless considered medically necessary. 
Preferably alternative antimicrobials and anti-HIV drugs would need to be prescribed to 
these patients.   
• 
OATP inhibitors:  Prohibited unless considered medically necessary 
• 
Anti-HIV drugs: atazanavir, lopinavir, nelfinavir, ritonavir, saquinavir, 
tipranavir 
• 
Anti-HCV drugs: simeprevir, telaprevir,  
• 
Antibiotics drugs: clarithromycin, erythromycin, rifampin/rifampicin 
• 
Antifungals drugs: itraconazole 
• 
Others: cyclosporine, eltrombopag, gemfibrozil 
 
For participants receiving bortezomib: 
• CYP3A4-inhibitors: Closely monitor when giving bortezomib in combination 
with potent CYP3A4-inhibitors. Co-administration with strong CYP3A4 

 
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inhibitors can increase bortezomib exposure by 35%. Monitor participants for 
signs of bortezomib toxicity and consider a bortezomib dose reduction, if 
necessary.  
• CYP3A4 inducers: Strong CYP3A4 inducers are not recommended in 
combination with bortezomib. Co-administration with strong CYP3A4 inducers 
may decrease bortezomib exposure by 45% or more, which may reduce 
bortezomib efficacy.  
• St. John’s Wort (Hypericum perforatum) may decrease bortezomib exposure 
unpredictably and should be avoided.  
• For further information see the most recently approved country-specific 
bortezomib label. 
6.6. 
Dose Modification and Delay 
Dose delays and reductions are permitted throughout the study as described below. 
After Cycle 1 Day 1, dose modifications may be made for individual participants based 
on safety findings. 
Dosing delays are also permitted for medical/surgical events or logistical reasons not 
related to study therapy (e.g., elective surgery, unrelated medical events, participant 
vacation, and/or holidays) but not for participant’s decision to delay treatment.  
For dose delays or interruptions lasting >42 days, the GSK Medical Monitor should be 
contacted to discuss the investigator’s plan for restarting treatment.  
For potential overlapping toxicities, such as hematologic toxicity, the investigator should 
use their clinical judgement on which agent should be dose-reduced first, or for severe 
toxicities, more than 1 agent can be held/ dose modified. Whenever possible, step-wise 
dose modification is recommended first in order to minimize the potential to compromise 
treatment efficacy. 
The reason for any dose delay must be documented in the participant's electronic case 
report form (eCRF) and clinic record. 
6.6.1. 
Belantamab Mafodotin 
The dose allowed for belantamab mafodotin may be reduced once from the starting dose 
(Dose Level -1). Participants not able to tolerate Dose Level -1, will permanently 
discontinue belantamab mafodotin treatment due to unacceptable toxicity (Section 7.1.1). 
Detailed guidance for belantamab mafodotin dose levels and AE-related dose 
modifications including dose modification guidelines for belantamab mafodotin 
treatment-related corneal events based on Keratopathy Visual Acuity (KVA) Scale  
(Appendix 9, Table 30) are shown in Table 9, Table 10, and Table 11. General guidance 
for belantamab mafodotin dose modifications and management of drug-related AEs 
otherwise unspecified is shown in Table 12. The guidance for dose delay is shown in 
Table 16. 

 
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Table 9 
Dose Levels Belantamab Mafodotin: Treatment Arm A 
Dose Level 
Belantamab Mafodotin Dose 
Starting Dose 
2.5 mg/kg IV q21 days  
Dose Level -1  
1.9 mg/kg IV q21 days  
 

 
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Table 10 
Dose Modification Guidelines for Adverse Events Associated with 
Belantamab Mafodotin 
Toxicity 
Grade/Symptoms 
Recommendations  
Serum Creatinine 
Graded according to 
NCI-CTCAE criteria 
Grade 2 
>1.5 - 3.0 x baseline; 
>1.5 - 3.0 x ULN 
• 
Repeat within 48 hours if elevation cannot be explained by 
concomitant sepsis, TLS, other severe condition with fever or 
dehydration. 
• 
If confirmed: withhold belantamab mafodotin, initiate 
treatment and monitoring as clinically indicated, and follow for 
resolution. 
• 
Discuss any further dosing with Medical Monitor 
Grade 3  
>3.0 x baseline; 
>3.0 - 6.0 x ULN 
Or 
Grade 4 
>6.0 x ULN 
• 
Provide appropriate medical treatment 
• 
If drug related, permanently discontinue treatment with 
belantamab mafodotin  
• 
If due to another cause (e.g. sepsis, dehydration), withhold 
treatment with Belantamab Mafodotin. Upon recovery to 
Grade 1, restart treatment at the same dose level. 
Spot Urine 
(albumin/creatinine 
ratios) 
>2000 mg/g 
(224 mg/mmol) 
• Re-test (at least 7 days apart) 
• If not confirmed, continue belantamab mafodotin at pre-held dose 
• If confirmed on re-test and no clear evidence of disease 
progression:a 
o 
Interrupt treatment with belantamab mafodotin 
o 
Repeat testing within 4 weeks 
o 
If spot urine ≤2000 mg/g (224 mg/mmol), may restart 
belantamab mafodotin with 1 dose level reduction 
o 
If spot urine remains >2000 mg/g (224 mg/mmol) after 
4 weeks, consider permanently discontinuing belantamab 
mafodotin and provide treatment as clinically indicated and 
follow for resolutiona. 
Urine dipstick for 
protein 
2+ 
• May continue belantamab mafodotin dosing 
• Confirm by quantitative assessment using either albumin/creatinine 
(spot urine from first void) performed at a local lab (or at a central 
lab if local lab is not available) 
• If albumin/creatinine 2000 mg/g, at the next cycle follow guidance 
given above for spot urine. 
3+ 
• Interrupt treatment and follow up for recovery. Implement 
quantification of albumin/creatinine ratio 
Thrombocytopenia 
(on days of dosing)  
 
Graded according to 
NCI-CTCAE criteria 
Grade 3 
• 
No bleeding: continue treatment with 1 dose level reduction. 
Consider reverting to previous dose once thrombocytopenia 
recovered to Grade 2, or less. 
• 
With bleeding: withhold the dose, continue treatment after 
recovery with 1 dose level reduction. 
• 
Consider additional supportive treatment (e.g., transfusion), as 
clinically indicated and per local practice. 
Grade 4 
• 
Withhold the belantamab mafodotin dose. Consider restarting with 
1 dose level reduction if recovered to Grade 3, only if there is no 
active bleeding at time of treatment restart 

 
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Toxicity 
Grade/Symptoms 
Recommendations  
• 
If thrombocytopenia is considered disease-related, is not 
accompanied by bleeding, and recovers with transfusion to >25 
x109/L, continuing treatment with dose reduction may be 
considered after discussion with the Medical Monitor. 
Afebrile neutropenia 
 
Graded according to 
NCI-CTCAE criteria 
Grade 3-4 (Defined 
as ANC <1.0x109/L) 
• 
If noted on Day 1 of any cycle, withhold belantamab mafodotin 
dose. 
• 
Resume belantamab mafodotin at pre-held dose once neutropenia 
recovers to Grade ≤ 2 (ANC ≥ 1.0x109/L) on Day 1 of a 
subsequent cycle. 
• 
Prophylactic antibiotics, per physician discretion and local 
institutional guidance. Consider growth factors.  
• 
Local guidance must be followed for hematological monitoring if 
more conservative than the protocol SoA specifications.  
• 
In cases of frequent recurrent neutropenia (ANC <1.0x109/L), 
consider dose reduction of belantamab mafodotin. 
Febrile neutropenia 
 
Graded according to 
NCI-CTCAE criteria 
Grade 3-4 (Defined 
as: single temp of 
38.3°C, or sustained 
38°C for >1 hr AND 
ANC <1.0x109/L) 
• 
Withhold belantamab mafodotin and immediately hospitalize 
participant with appropriate management, per local institutional 
guidance. 
• 
Consider additional supportive treatment per local practice (e.g. 
growth factors). 
• 
Upon recovery, consider dose reduction of belantamab mafodotin, 
if neutropenia was drug-related. 
Infusion Reaction 
Graded according to 
NCI-CTCAE criteria 
Grade 2 
• 
Stop the infusion, provide medical treatment and continue at a 
reduced rate after resolution to Grade 0-1 
Grade 3 
• 
Further treatment with belantamab mafodotin needs to be 
discussed with Medical Monitor. Continuation only allowed after 
recovery to  Grade 1 and with premedication, and extension of 
infusion time to 2-4 hours. Any future infusion needs to be 
premedicated. 
Grade 4 
• 
Permanently discontinue 
Pneumonitis 
Graded according to 
NCI-CTCAE criteria 
Grade 2 
• 
Withhold treatment with belantamab mafodotin  
• 
Upon recovery, restart treatment with 1 dose level reduction.  
• 
If patient is already at the lowest dose level (1.9 mg/kg), then 
rechallenge with the same dose must be discussed with the 
medical monitor  
Grade 3-4 
• 
Permanently discontinue treatment with belantamab mafodotin  
a) Medical Monitor may consult GSK’s nephrology panel about plans to continue therapy. 
 

 
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Table 11 
Dose Modification Guidelines for Belantamab Mafodotin Treatment-
Related Corneal Events based on KVA1 Scale  
Grade per KVA scale 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Recommended 
Dosage Modifications2 
Continue 
treatment at 
current dose. 
Withhold 
belantamab 
mafodotin until 
improvement in 
either corneal 
examination 
findings or 
changes in BCVA 
to Grade 1 or 
better and resume 
at same dose. 
Withhold 
belantamab 
mafodotin until 
improvement in 
either corneal 
examination findings 
or changes in BCVA 
to Grade 1 or better 
and resume at 
reduced dose (1 
level)3 
 
Consider re-
escalating after at 
least 2 ophthalmic 
assessments post 
treatment re-
initiation, for events 
that do not worsen 
after resuming at 
lower dose and 
following benefit/risk 
assessment and 
discussion with the 
Sponsor. 
Permanently 
discontinue 
belantamab 
mafodotin.  
 
Patient may be re-
challenged on a 
case-by-case basis 
at a reduced dose 
after improvement 
and following 
benefit/risk 
assessment and 
discussion between 
the eye care 
specialist, the 
investigator, and 
the Sponsor.  
BCVA = best corrected visual acuity; KVA = Keratopathy Visual Acuity. 
1. Refer to Section 10.9, Appendix 9, Table 30 for Keratopathy Visual Acuity Scale for Treatment-related Corneal 
Events.  
2. Dose modification should be based on the most severe grade. If eyes differ in severity, dose modification guideline 
should be applied based on the more severe eye. 
3. If already on reduced dose (1.9 mg/kg), participant should resume treatment at that dose. 
 
Table 12 
General Dose Modification and Management Guidelines for Drug-
Related Adverse Events Not Otherwise Specified 
Severitya 
Management 
Follow-up 
Grade 1 
• 
Administer symptomatic 
treatment as appropriate 
• 
Continue study drug(s)b 
• 
Provide close follow-up to evaluate for increased 
severity, no dose modification necessary 
Grade 2 
• 
Administer symptomatic 
treatment 
• 
Investigate etiology 
• 
Consider consulting 
subspecialist, and/or diagnostic 
procedure 
Symptoms resolved in ≤7 days: 
• 
Continue after resolution at the current dose 
Symptoms ongoing >7 days or worsening: 
• 
Delay study drugc, or consider at the same dose level  
• 
If recovery takes >3 weeks, consult GSK MM  
• 
If symptoms continue or worsen to Grade 3-4, see 
below 

 
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Severitya 
Management 
Follow-up 
Grade 3 
• 
Provide appropriate medical 
treatment 
• 
Consider consulting 
subspecialist 
• 
Delay treatment till recovery to Grade 1 or less.  
• 
Consider restarting at the same dose level  
• 
Consider consultation with GSK MM.  
Exceptions: Participants who develop Grade 3 
toxicities which respond to standard treatment and 
resolve to ≤Grade 1 within 48 hours may continue 
treatment at scheduled dose  
Grade 4 
• 
Provide appropriate medical 
treatment 
• 
Consider consulting 
subspecialist 
• 
Discuss with Sponsor/Medical 
Monitor 
• 
Interrupt treatment.  
• 
Further treatment with belantamab mafodotin only 
allowed on individual basis if in the discussion with 
MM it is agreed that benefits outweigh the risks for a 
given participant 
a. 
Graded according to NCI-CTCAE v5.0 criteria. 
b. 
Treatment-related decisions can be made based on local laboratory results if central results are not available 
or delayed. 
c. 
In case a dose is delayed, the participant should wait for the next scheduled dose to resume treatment. 
 
6.6.2. 
Daratumumab 
Detailed guidance for daratumumab dose delays is shown in Table 17. No daratumumab 
dose modifications are permitted, in line with the most recently approved country-
specific IV daratumumab label. 
The daratumumab dose should be delayed if any of the following criteria are met: 
• Grade 4 hematologic toxicity, or Grade 3 or higher thrombocytopenia with 
bleeding 
• Grade 3 or higher non-hematologic toxicities with the following exceptions: 
– Grade 3 nausea or Grade 3 vomiting that responds to antiemetic treatment 
– Grade 3 diarrhea that responds to antidiarrheal treatment 
– Isolated Grade 3 gamma-glutamyltransferase elevation 
– Grade 3 fatigue or asthenia that was present at baseline or that lasts for <7 
days after the last administration of daratumumab. 
Daratumumab dosing should be resumed when the toxicity has resolved to ≤ Grade 2. 
See Table 17 for guidance on treatment windows. 
For guidance on infusion-related reactions see Section 7.1.4. 
6.6.3. 
Bortezomib 
Detailed guidance for bortezomib dose reductions and delays is shown in Table 16 and 
Table 17. 

 
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If the decision is made to permanently discontinue bortezomib, but belantamab mafodotin 
(Arm A) or daratumumab (Arm B) treatment continues, a participant may remain in the 
trial and continue treatments and assessments as described in the SoA (Section 1.3).  
Dose adjustments should be based on the highest grade of toxicity that is attributed to 
bortezomib. Bortezomib therapy should be withheld at the onset of any Grade 3 non-
hematological or Grade 4 hematological toxicities excluding neuropathy. Once the 
symptoms of the toxicity have resolved, bortezomib therapy may be reinitiated at a 
reduced dose per approved labeling [Velcade USPI, 2021], as described in Table 13 and 
Table 14. 
Table 13 
Dose Levels for Bortezomib 
Dose Level 
Bortezomib Dose 
Starting Dose 
1.3 mg/m2 
Dose Level -1  
1.0 mg/m2 
Dose Level -2 
0.7 mg/m2 
Dose Level -3 
Discontinue bortezomib 
 

 
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Table 14 
Dose Modification Guidelines for Hematologic and Other Toxicities 
Associated with Bortezomib and Dexamethasone Treatment 
Toxicity 
Gradea 
Recommendations 
Hematological toxicityb 
Grade ≥ 4 
• 
Withhold bortezomib therapy until symptoms of toxicity 
have resolved. 
• 
Bortezomib may be reinitiated with 1 dose level 
reduction (from 1.3 mg/m2 to 1 mg/m2, or from 1 mg/m2 
to 0.7 mg/m2). 
Non-hematological 
toxicities (excluding 
peripheral neuropathy)b 
Grade ≥3 
• 
Withhold bortezomib therapy until symptoms of toxicity 
have resolved. Then, bortezomib may be reinitiated 
with a 1 dose level reduction (from 1.3 mg/m2 to 1 
mg/m2, or from 1 mg/m2 to 0.7 mg/m2). 
• 
For bortezomib-related neuropathic pain and/or 
peripheral neuropathy, hold or modify bortezomib as 
outlined below and in Table 5 of the package inserts 
[Velcade USPI, 2021] 
Peripheral neuropathyc 
Grade 1 
• 
Defined as clinical or diagnostic observations only 
• 
Grade 1 Asymptomatic, without pain or loss of function 
– No action needed 
• 
Grade 1 with pain: reduce bortezomib dose to 1 mg/m2 
Grade 2 
• 
Defined as moderate symptoms; limiting instrumental 
Activities of Daily Living (ADL)d 
• 
Grade 2 with no pain: reduce bortezomib dose to 1 
mg/m2 
• 
Grade 2 with pain: withhold bortezomib therapy until 
toxicity resolves. When toxicity resolves reinitiate with a 
reduced dose of bortezomib at 0.7 mg/m2 once per 
week 
Grade 3 
• 
Defined as severe symptoms; limiting self-care ADLe 
• 
Grade 3: withhold bortezomib therapy until toxicity 
resolves. When toxicity resolves reinitiate with a 
reduced dose of bortezomib at 0.7 mg/m2 once per 
week 
Grade 4 
• 
Defined as life-threatening consequences; urgent 
intervention indicated 
• 
Discontinue bortezomib 
a. 
Grading based on NCI-CTCAE v5.0. 
b. 
Criteria and recommendations taken from Section 2.6 and Table 2 of the package inserts [Velcade USPI, 
2021]. 
c. 
Criteria and Recommendations for Peripheral Neuropathy are taken from Section 2.7 and Table 5 of the 
package inserts [Velcade USPI, 2021]. 
d. 
Instrumental ADL: refers to preparing meals, shopping for groceries or clothes, using telephone, managing 
money etc. 
e. 
Self-care ADL: refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden. 
f. 
Data source: Table 2, Table 5 and Section 2.6 of the package inserts [Velcade USPI, 2021]. 

 
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6.6.4. 
Dexamethasone 
Starting dose of dexamethasone may be reduced to 10 mg for participants older than 75 
years of age, who have a body-mass index of less than 18.5, who had previous 
unacceptable side effects associated with glucocorticoid therapy, or who are unable to 
tolerate the starting dose (For guidance on further dose modification, see Table 15). 
For participants with contraindications to the starting dose regimen of dexamethasone in 
combination with bortezomib, or who are intolerant to this regimen, the dose of 
dexamethasone can be reduced to Dose Level -1. If Dose Level -1 is not tolerated, the 
dexamethasone dose can be reduced to Dose Level -2. If this is also not tolerated, 
dexamethasone should be discontinued (Table 15). 
Table 15 
Permitted Dose Reductions for Dexamethasone in Both Arms 
Dose Level 
≤75 years of age 
>75 years of age, BMI ≤ 18.5 
Kg/m2 
Starting dose 
20 mg 
10 mg 
Dose level -1   
12 mg 
6 mg 
Dose level -2*  
8 mg 
4 mg 
*Dexamethasone could be reduced further than Dose Level -2 per investigator discretion. 
 
If bortezomib dosing is delayed or discontinued, dexamethasone dosing could continue 
per investigator discretion and local institutional guidelines. 
In Arm B, corticosteroid should be given prior to each daratumumab infusion as 
described in Section 6.1.4.1. 
6.6.5. 
Guidance on Dose Delays for Treatment Arm A and B 
Table 16 and Table 17 provide guidance on dose delays for Treatment Arm A and 
Treatment Arm B, respectively.  
A cycle is defined as a planned dosing period in which any study treatment (belantamab 
mafodotin (Arm A) or daratumumab (Arm B), and/ or bortezomib, dexamethasone is 
administered (and can be either 3 weeks or 4 weeks in duration). The start of a cycle is 
the date the first study treatment agent is administered; a cycle has not started unless a 
study treatment agent has been administered. 
In any dosing delay scenario, Q3W assessments should continue to be carried out as 
described in the SoA. For treatment delays within the treatment window, subsequent 
treatment dates will not be adjusted. 
In Arm B, if there are dosing delays, the switch to Q4W dosing for daratumumab will be 
after 14 doses of daratumumab (as per the daratumumab label), or after 8 full or truncated 
cycles of bortezomib, whichever is soonest. 

 
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Table 16 
Dose Delays for Treatment Arm A (Cycles 1-8 only) 
Scenario 
Actions for Belantamab Mafodotin 
Actions for bortezomib 
1. Delay of only 
belantamab mafodotin 
After Cycle 1, a window of 3 days is 
acceptable for belantamab mafodotin 
dosing. Outside this window, treatment 
should be given on D1 of the next planned 
cycle.  
Continue bortezomib according to the 
regimen outlined in the SoA, until 
completion of 8 full or truncated cycles of 
bortezomib. 
2. Delay of only 
bortezomib 
Continue belantamab mafodotin according 
to the regimen outlined in the SoA. 
Bortezomib should be administered on the 
planned treatment day. If treatment cannot 
be administered as planned, when a 
participant is ready to resume treatment, 
bortezomib may be re-started at the 
appropriate point in the planned dosing 
regimen, e.g., if the participant is unable to 
receive bortezomib on D1 and D4 of a 
given cycle, treatment could resume on 
D8 or D11, and missed D1 and D4 doses 
will not be made up. 
3. Delay of both 
belantamab mafodotin 
and bortezomib ≤21 
days (Cycles 1-8) 
Bortezomib can be resumed at the appropriate point in the cycle, e.g., in Cycles 1-8, if 
the participant is unable to receive bortezomib on D1 and D4, resume treatment with 
bortezomib on D8 or D11.  
Belantamab mafodotin should be administered on D1 of the next planned cycle. 
Visits and assessments should continue to occur as specified in the SoA until treatment 
is restarted. 
4. Delay of both 
belantamab mafodotin 
and bortezomib >21 
days (Cycles 1-8) 
Follow the guidance as outlined in 
Scenario 1 above. 
Follow the guidance as outlined in 
Scenario 2 above. 
 
Table 17 
Dose Delays for Treatment Arm B (Cycles 1-8) 
Scenario 
Actions related to daratumumab 
Actions related to bortezomib 
1. Delay of only 
daratumumab 
For Cycles 1-3, a window of ±1 day is 
acceptable for daratumumab dosing. 
After Cycle 3, a window of ±3 days is 
acceptable for daratumumab dosing. 
Outside these windows, treatment should 
be given on the next planned dosing day. 
If 8 cycles of bortezomib are administered 
without all 14 planned doses of 
daratumumab being administered, 
participants should move to the Q4W 
daratumumab dosing regimen. 
Continue bortezomib according to the 
regimen outlined in the SoA. 
If 8 full or truncated cycles of bortezomib 
are administered without all 14 planned 
doses of daratumumab being 
administered, participants should move to 
the Q4W daratumumab dosing regimen. 
2. Delay of only 
bortezomib 
Continue daratumumab according to the 
regimen outlined in the SoA. 
Bortezomib should be administered on 
the planned treatment day. If treatment 

 
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Scenario 
Actions related to daratumumab 
Actions related to bortezomib 
Switch to Q4W administration of 
daratumumab when either 8 full or 
truncated cycles of bortezomib have been 
administered OR after 14 doses of 
daratumumab have been administered, 
whichever is soonest. 
cannot be administered as planned, when 
a participant is ready to resume 
treatment, bortezomib may be re-started 
at the appropriate point in the planned 
dosing regimen, e.g., if the participant is 
unable to receive bortezomib on D1 and 
D4 of a given cycle, treatment could 
resume on D8 or D11, and missed D1 
and D4 doses will not be made up. 
3. Delay of both 
daratumumab and 
bortezomib ≤21 days 
(Cycles 1-8) 
Bortezomib can be resumed at the appropriate point in that cycle, e.g., in Cycles 1-8, if 
the participant is unable to receive bortezomib on D1 and D4, resume treatment with 
bortezomib on D8 or D11.  
Daratumumab should be administered on the next planned dosing day (e.g., in Cycles 
1-3, on either D1, D8 or D15 and in Cycle 4 onwards on D1 of the next cycle). 
Visits and assessments should continue to occur as specified in the SoA until 
treatment is restarted. 
4. Delay of both 
daratumumab and 
bortezomib >21 days 
(Cycles 1-8) 
Follow the guidance as outlined in 
Scenario 1 above. 
Follow the guidance as outlined in 
Scenario 2 above. 
6.6.6. 
Management of Hepatitis B+ participants 
• Management by local hepatology or infectious disease services is required.  If no 
subspecialist support is available, consultation with GSK Medical Monitor is required 
prior to enrolment into the study for participants with positive titres to Hepatitis B. 
 
• Participants should be monitored according to SoA Table 4. 
 
• Participants who experience clinically significant elevations in liver chemistry should 
follow liver event monitoring and stopping criteria (Section 7.1.2 and Appendix 4), 
and careful evaluation should be immediately initiated for evaluation of etiology 
including HBV DNA testing.  
 
• Participants who develop detectable HBV DNA levels during study treatment 
should be reviewed by local specialist(s) immediately (within 1 week) and 
appropriate therapy and monitoring instituted. 
 
• Study treatment should be withheld, and GSK Medical Monitor should be 
contacted for any participant who develops detectable HBV DNA levels. 
 

 
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Table 18 
Dose Modification Guideline for Hepatitis B Reactivation 
Toxicity 
Grade/description of 
toxicity 
Recommendations 
Hepatitis B 
reactivation 
Detectable HBV DNA 
• Immediate consult with local specialist to 
institute/modify treatment 
• Hold study treatment 
• Contact GSK Medical Monitor promptly - 
agreement with Medical Monitor must be 
obtained prior to further dosing of study 
treatment 
• Follow liver monitoring/stopping guidelines 
per protocol for elevation in liver function 
tests. 
 
6.7. 
Intervention After the End of the Study 
There is no planned intervention following the EOS. The investigator is responsible for 
ensuring that consideration has been given to the post-study care of the participant’s 
medical condition. 
Participants who have not progressed at the time of the final OS analysis (EOS) may be 
offered belantamab mafodotin for further treatment until progression or unacceptable 
toxicity, if considered appropriate based on the study results.  
Refer to the SoA for follow-up assessments of participants who are to be followed for 
disease progression and survival after they permanently discontinue from study 
treatment. 

 
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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Intervention 
Participants will receive study treatment according to the SoA (Section 1.3). Study drug 
must be permanently discontinued in the case of: 
• 
Disease progression, as defined by IMWG criteria [Kumar, 2016], or 
unacceptable toxicity 
• 
Participant has met any of the protocol defined safety stopping criteria 
• 
Pregnancy  
Before discontinuing study treatment strictly due to disease progression, sites must 
contact the GSK Medical monitor to confirm progression meets IMWG criteria [Kumar, 
2016]. The GSK Medical monitor will review the central laboratory results as well as 
imaging results (if applicable) to confirm progressive disease as per IMWG criteria.  If 
progressive disease criteria are not met, the investigator retains the decision to determine 
if treatment should be discontinued. However, the reason for treatment discontinuation 
should only be documented as disease progression if IMWG criteria for confirmed 
disease progression are met.  
Note: As per IMWG criteria: All response categories require two consecutive 
assessments made at any time before the institution of any new therapy; all categories 
also require no known evidence of progressive or new bone lesions or extramedullary 
plasmacytomas if radiographic studies were performed. 
 
In addition, study treatment may be permanently discontinued for any of the following 
reasons: 
• 
Deviation(s) from the protocol 
• 
Request of the participant or proxy (withdrawal of consent by participant or 
proxy) 
• 
Investigator’s discretion 
• 
Participant is lost to follow-up  
• 
All or part of the study is closed or terminated 
If the participant voluntarily discontinues from treatment due to toxicity, the adverse 
event (AE) will be recorded as the primary reason for permanent discontinuation on the 
electronic case report form (eCRF).  
Once a participant has permanently discontinued from a study treatment, the participant 
will not be allowed to restart study treatment. 

 
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All participants who permanently discontinue study treatment will have safety 
assessments at the time of discontinuation and during End of Treatment (EOT) follow-up 
as specified in Table 1 or Table 2. 
All participants must be followed for survival, up to the end of study as defined in the 
protocol. Discontinuation of study treatment does not impact a participant’s participation 
in the study. The participant should comply to the protocol schedule of assessments and 
data collection should continue. Where permitted, data from publically available death 
registers will be used for participants withdrawn from study or lost to follow-up prior to 
death. 
Site personnel, or an independent third party, will attempt to collect the vital status of the 
participant within legal and ethical boundaries for all participants randomized, including 
those who did not get study intervention. Where permitted, public sources may be 
searched for vital status information. If vital status is determined as deceased, this will be 
documented and the participant will not be considered lost to follow-up. Sponsor 
personnel will not be involved in any attempts to collect vital status information. 
If the participant does not agree to continue in-person visits, a modified follow-up must 
be arranged to ensure the collection of endpoints and safety information. This could be a 
telephone contact with the participant, a contact with a relative or treating physician, or 
collecting information from medical records. The approach taken should be recorded in 
the medical records. A participant who agrees to modified follow-up is not considered to 
have withdrawn consent or to have withdrawn from the study. 
Participants who permanently discontinue study treatment for reasons other than disease 
progression will remain in the study and will be followed for PFS according to the 
protocol schedule described in Section 1.3 until: 
• 
Disease progression according to IMWG criteria  
• 
New anti-myeloma therapy is initiated  
• 
Death 
• 
Withdrawal of consent 
• 
Loss to follow-up 
• 
End of study  
Participants with documented disease progression whilst on treatment, or during PFS 
follow-up, will be followed for PFS2 and OS until death, withdrawal of consent, loss to 
follow-up or the end of study (as described in Section 4.4), whichever occurs first. 
7.1.1. 
Discontinuation of Individual Components of Combination Study 
Treatment 
At the discretion of the investigator, participants meeting the stopping criteria for 
bortezomib and dexamethasone may continue belantamab mafodotin (Arm A) or 
daratumumab (Arm B) monotherapy until PD, unacceptable toxicity, or death occurs or 
end of study. Similarly, participants meeting the stopping criteria for belantamab 

 
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mafodotin (Arm A) or daratumumab (Arm B) may continue bortezomib and 
dexamethasone until completion of 8 cycles (after which they should attend an End of 
Treatment Visit and be followed up according to the SoA), PD, unacceptable toxicity, or 
death (whichever occurs first). The primary reason for discontinuation of each study 
treatment must be documented independently in the medical record and on the eCRF. 
7.1.2. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to assure 
participant safety and evaluate liver event etiology. Discontinuation of study treatment 
for abnormal liver tests is required when the participant satisfies any of the stopping rules 
as shown in Figure 4. 
Figure 4 
Liver Stopping and Monitoring Event Algorithm (ALT ≥ 3xULN) 
 
ALT = alanine aminotransferase; INR = international normalized ratio; SAE = serious adverse event; Total bili = total 
bilirubin; ULN = upper limit of normal. 
 
Refer to Section 10.4 for required Liver Safety Actions and Follow up Assessments and 
for required process for study intervention restart/rechallenge if considered for the 
participant. 

 
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Figure 5 
Liver Stopping and Monitoring Event Algorithm for ALT ≥ 3xULN but 
<8xULN 
 
ALT = alanine aminotransferase; INR = international normalized ratio; SAE = serious adverse event; Total bili = total 
bilirubin; ULN = upper limit of normal. 
 
Refer to Section 10.4 for required Liver Safety Required Actions and Follow-up 
Assessments and for required process for study intervention restart/rechallenge if 
considered for the participant. 
7.1.2.1. 
Study Intervention Restart or Rechallenge after Liver Stopping Criteria 
Are Met 
A participant who met liver chemistry stopping criteria cannot resume study intervention 
unless all of the following conditions are met: 
• 
GSK approval is granted (as described below), 
• 
Institutional Review Board/Independent Ethics Committee (IRB/IEC) 
approval is obtained, if required, and 
• 
Separate ICF for study intervention restart/rechallenge is signed by the 
participant and participant is informed of any associated risks 
If GSK approval to restart/rechallenge participant with study intervention is not granted, 
then participant must permanently discontinue study intervention and may continue in the 
study for protocol-specified follow up assessments. 
Refer to Section 10.4 and the SRM for full guidance. 

 
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7.1.3. 
Corneal Event Stopping Criteria 
Dose modifications and stopping criteria of belantamab mafodotin for treatment-related 
corneal events (Table 11) should be based on grading of corneal events according to the 
guidelines of Keratopathy Visual Acuity (KVA) Scale (Section 10.9, Appendix 9, Table 
30). 
Participants who develop Grade 4 corneal events according to the KVA Scale must be 
discussed in detail between the treating qualified eye care specialist (Appendix 10), the 
GSK Medical Monitor and possibly a third party ophthalmologist, in order to determine 
whether the participant can be allowed to continue treatment with belantamab mafodotin, 
or permanently discontinue treatment (Table 11). If a participant is allowed to continue 
treatment, the dose of belantamab mafodotin will be reduced by 1 dose level (Section 
6.6.1). The decision will be documented in study files, together with individual 
assessment of risk-benefit. 
7.1.4. 
Infusion-Related Reactions Stopping Criteria 
7.1.4.1. 
Belantamab Mafodotin 
Premedication is not required prior to infusion unless deemed medically appropriate by 
the investigator following evaluation of infusion-related reactions (IRRs). Premedication 
should be considered in any participant who experienced an IRR at first or any 
subsequent infusion with belantamab mafodotin. For infusion reactions of any 
grade/severity, immediately interrupt the belantamab mafodotin infusion and manage 
symptoms. Once reaction symptoms resolve, resume the infusion at a reduced rate. 
Premedication may be required with subsequent infusions (Section 6.1.3.1). 
A participant that experiences a Grade 4 IRR associated with belantamab mafodotin 
should be permanently withdrawn from the study. 
7.1.4.2. 
Daratumumab 
Pre/post-medication should be given for every daratumumab infusion as described in 
Section 6.1.4.1. 
For infusion reactions of any grade/severity, immediately interrupt the daratumumab 
infusion and manage symptoms. Management of infusion reactions may further require 
reduction in the rate of infusion, or permanent discontinuation of study treatment as 
outlined in the most recently approved country-specific IV daratumumab label and 
below. 
• Grade 1-2 (mild to moderate): Once reaction symptoms resolve, resume the 
infusion at no more than half the rate at which the reaction occurred. If the 
participant does not experience any further reaction symptoms, infusion rate 
escalation may resume at increments and intervals as clinically appropriate up to 
the maximum rate of 200 mL/hour (refer to Pharmacy Manual and local/regional 
label [if applicable] for infusion rates). 

 
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• Grade 3 (severe): Once reaction symptoms resolve, consider restarting the 
infusion at no more than half the rate at which the reaction occurred. If the 
participant does not experience additional symptoms, resume infusion rate 
escalation at increments and intervals as outlined in the Pharmacy Manual and 
local/regional label (if applicable) for infusion rates. Repeat the procedure above 
in the event of recurrence of Grade 3 symptoms. Permanently discontinue 
daratumumab upon the third occurrence of a Grade 3 or greater infusion reaction. 
• Grade 4 (life threatening): Permanently discontinue daratumumab treatment. 
7.1.5. 
Allergic Reactions and Anaphylactic Reactions Stopping Criteria 
All participants will be monitored carefully for evidence of allergic response to treatment. 
A participant that exhibits signs or symptoms of severe hypersensitivity or anaphylaxis 
will receive appropriate medical treatment and will permanently discontinue study 
treatment. 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
• 
A participant may withdraw from the study at any time at his/her own request, 
or may be withdrawn at any time at the discretion of the investigator for safety, 
behavioral, compliance or administrative reasons. This is expected to be 
uncommon. 
• 
At the time of withdrawal from the study, if possible, an End of Treatment Visit 
should be conducted, as shown in the SoA (Section 1.3). See SoA for data to be 
collected at the End of Treatment Visit. 
• 
The participant will be permanently discontinued both from the study 
intervention and from the study at that time. 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. 
• 
If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the investigator must document this in the site 
study records. 
• 
Withdrawn participants will not be replaced. 
7.3. 
Lost to Follow Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit 
as soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 

 
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• 
Before a participant is deemed lost to follow up, the investigator or designee 
must make every effort to regain contact with the participant (where possible, 
telephone calls and, if necessary, a certified letter to the participant’s last known 
mailing address or local equivalent methods). These contact attempts should be 
documented in the participant’s medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study. 
Site personnel, or an independent third party, will attempt to collect the vital status of the 
participant within legal and ethical boundaries for all participants randomized, including 
those who did not get study intervention. Where permitted, public sources may be 
searched for vital status information. If vital status is determined as deceased, this will be 
documented and the participant will not be considered lost to follow-up. Sponsor 
personnel will not be involved in any attempts to collect vital status information. 
Discontinuation of specific sites or of the study as a whole are detailed in 
Section 10.1.10. 

 
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8. 
STUDY ASSESSMENTS AND PROCEDURES 
A signed, written informed consent form must be obtained from the participant prior to 
any study-specific procedures or assessments being performed. The timing of each 
assessment is listed in the Schedule of Activities (Section 1.3).  
Whenever vital signs, 12-lead electrocardiograms (ECGs), and blood draws are scheduled 
for the same nominal time, the assessments must occur in the following order: 12-lead 
ECG, vital signs, blood draws. The timing of the assessments must allow the blood draw 
to occur at the exact nominal time. Detailed procedures for obtaining each assessment are 
provided in the SRM and Lab Manual. 
• 
Study procedures and their timing are summarized in the SoA (Section 1.3).  
• 
Protocol waivers or exemptions are not allowed.  
• 
Demographic and baseline assessments will include year of birth, sex, race, and 
ethnicity, where allowed.  Collection of sex, race and ethnicity data are 
necessary to assess and monitor the diversity of the study participants, and to 
determine if the study participants are truly representative of the impacted 
population. 
• 
Medical/medication/family history will be assessed as related to the 
inclusion/exclusion criteria listed in Section 5.1 and Section 5.2. 
• 
Immediate safety concerns must be discussed with the sponsor immediately 
upon occurrence or awareness to determine if the participant should continue or 
discontinue study treatment. 
• 
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 
(e.g., blood count) and obtained before signing of ICF may be utilized for 
screening or baseline purposes provided the procedure met the protocol-
specified criteria and was performed within the time frame defined in the SoA 
(Section 1.3). 
• 
Survival follow-up can be conducted by chart review, phone call, or any other 
form of communication as laid out in the SoA.  
• 
Visit windows: 
– Baseline disease assessments must be completed within 28 days prior to 
dosing start unless otherwise specified. Refer to the SoA in Section 1.3.  
– Screening assessments performed within the permitted time need not be 
repeated on C1D1 unless otherwise specified. 

 
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– Safety labs completed within 72 hours of first dose do not need to be repeated 
on C1D1. 
– Pregnancy testing must be completed within 72 hours prior to first dose. 
– Imaging must be completed within 30 days prior to first dose. 
– On-study Q3W assessments have a ±3-day window. 
– After C1D1, on-study ocular exams should be performed within 5 days prior 
to dosing. 
–  Follow-up Visits have a ±3-day window. 
– Overall Survival Follow-up Visits have a ±14-day window. 
For details on Home Healthcare and Telemedicine Approaches, please refer to Appendix 
15. 
A list of clinical laboratory tests required during the study is included in Table 19. 
Table 19 
List of Clinical Laboratory Tests 
Hematology1 
Platelet count  
Red Blood Cell 
(RBC) Indices: 
MCV 
MCH 
MCHC 
Automated WBC Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC count 
White blood cell (WBC) count (absolute)  
Hemoglobin 
Hematocrit 
Clinical Chemistry1 
Creatinine 
Potassium 
Aspartate aminotransferase 
(AST) 
Total and direct bilirubin 
Glucose  
Chloride 
Alanine aminotransferase 
(ALT) 
Uric acid 
Sodium 
Total bicarbonate 
Gamma glutamyl 
transferase (GGT) 
Albumin 
Magnesium 
Calcium 
Alkaline phosphatase 
Total protein 
eGFR 
Phosphorous 
Creatine kinase (CK) 
Lactate dehydrogenase 
(LDH) 
Urine1 
Urine dipstick6 for protein OR Spot Urine (from first void) for albumin/creatinine ratio3   
Other Laboratory Tests (as indicated in Section 1.3)
HbA1c1; Pregnancy Test (urine or blood)1; Follicle-stimulating hormone (FSH)1 and estradiol1 (as needed in women of 
non-childbearing potential only); Hepatitis B surface antigen (HBsAg)1; Hepatitis B core antibody (HBcAb)1, 
Hepatitis C antibody, Hepatitis C RNA test1,3 (optional), blood type assessment1, indirect antiglobulin test1. 
Note: Hepatitis C RNA testing is optional but must be done to determine participant eligibility if hepatitis C antibody 
positive. 
PK and ADA
2 
Belantamab mafodotin pharmacokinetics (PK) 
Anti-drug antibodies (ADA) to belantamab mafodotin

 
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Disease Evaluation Laboratory Tests 
Urine protein 
electrophoresis (UPEP)2 
Serum immunofixation2 
Ca corrected for albumin 
(serum)2 
 
Serum protein 
electrophoresis (SPEP)2 
Urine immunofixation2 
IgG, IgM, IgA, IgD/IgE2,4 
 
Serum kappa/lambda free 
light chain (FLC) ratio2 
24-hour urine collection for 
M protein2 
Beta-2 microglobulin2 
 
Biomarker Measurements2  
sBCMA (serum), cfDNA (plasma)
Optional Testing2,5  
Pharmacogenomics sample5
1. 
To be performed at local laboratory. 
2. 
To be performed at central laboratory. 
3. 
If not available locally it can be performed centrally. Spot Urine (albumin/creatinine) testing: i) does not need to 
be repeated on C1D1 if conducted within 7 days of C1D1 dosing (in case of screening assessment), and ii) does 
not need to be repeated on D1 of subsequent cycles if conducted within 5 days of D1 dosing of a given cycle (C2 
onwards). 
4. 
Only for participants with IgD/E myeloma. 
5. 
Informed consent for optional samples (genetic research) must be obtained before collecting a sample. 
6. 
Urine dipstick for protein should be performed at a local lab (If albumin/creatinine ratio not available locally, then 
at a central lab). Albumin/Creatinine ratio needs to be done in any patient with urine dipstick protein result of 1+ 
(for screening), and in any patient with 2+ (on study) or with positive protein if urine dipstick protein 
quantification is not available.  
 
8.1. 
Efficacy Assessments 
The primary endpoint of this study is PFS. Standard disease assessments for RRMM will 
include the following assessments:  
• 
Urine protein electrophoresis (UPEP), urine immunofixation, 24-hour collection 
for urine M-protein  
• 
Serum protein electrophoresis (SPEP), serum M-protein, serum immunofixation 
• 
Calcium corrected for albumin 
• 
IgG, IgM, IgA 
• 
IgD, IgE (only in participants with IgD or IgE myeloma)  
• 
Serum kappa, lambda free light chain (FLC) ratio  
• 
Bone marrow (aspirate and biopsy) at screening and to confirm CR/sCR. 
Additional BM testing if CR is achieved: biopsy for immunohistochemistry 
(IHC) to confirm sCR. BM aspirate for MRD at screening and at MRD 
assessments (Section 8.1.3). 
• 
PET-CT is required for participants that achieve MRD-negative status, at the 
time of achieving this status (within 42 days [6 weeks] of the availability of 
MRD results) (Section 8.1.3). 
• 
Imaging of extramedullary disease (in participants with extramedullary disease) 
or if a new lesion is suspected for confirmation of progressive disease 

 
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• 
Physical examination (as indicated for palpable/superficial lesions) 
• 
Skeletal surveys at screening and as clinically indicated 
Response evaluation will be performed according to the IMWG Uniform Response 
Criteria for Multiple Myeloma [Kumar, 2016]. 
Baseline serum/urine disease assessment will be completed during the Screening period 
(within 28 days prior to the first dose of study treatment) and baseline imaging within 30 
days prior to the first dose of study treatment. On study serum and urine-based 
assessments (M-protein, FLC, ± immunofixation) will be performed every 3 weeks. 
Details for the preparation and shipment of samples for central laboratory assessments 
will be provided in the Lab Manual. 
In participants with extramedullary myeloma, the disease assessments must include 
imaging (e.g., CT, MRI, or PET-CT scans: the same method should be used throughout 
the study) and physical examination (as indicated for palpable/superficial lesions).  
For participants who are followed by imaging for extramedullary disease the imaging 
should be performed as described in the SoA (Section 1.3).  
All efficacy assessments must be performed on a calendar schedule and must not be 
affected by dose interruptions/delays. For post-baseline assessments, a window of ±3 
days is permitted to allow for flexible scheduling. 
For participants who are discontinuing study intervention due to PD, the confirmation of 
laboratory parameters must be performed from a different blood collection either on the 
same day, or within 14 days of the original date of suspected disease progression, 
preferably before institution of any new anti-myeloma therapy. The assessments to be 
performed during the End of Treatment Visit are described in the SoA. If the last imaging 
assessment was greater than or equal to 8 weeks prior to the participant’s discontinuation 
from study treatment and progressive disease has not been documented, a new disease 
assessment must be obtained at the time of discontinuation from study treatment. For 
participants with PD due to extramedullary disease, confirmatory scans are not required. 
The laboratory parameters do not need to be repeated if the extramedullary disease is the 
only site of progression. 
8.1.1. 
Response Evaluation 
Response will be assessed according to the IMWG criteria [Kumar, 2016], as determined 
by a blinded IRC, as well as by the investigator. 
8.1.2. 
Assessment of CR Where Daratumumab Interference is 
Suspected 
Daratumumab is an IgG kappa monoclonal antibody that can be detected in serum 
electrophoresis and immunofixation assays. This can have an impact on the detection of 
CR and/or disease progression in participants who achieve CR/sCR with IgG kappa 
myeloma. Participants in Arm B with IgG kappa myeloma and suspected PD, or with 
VGPR and suspected CR, are required to undergo central testing with a daratumumab-

 
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specific immunofixation assay to confirm PD or CR/sCR (see Lab Manual for further 
details). 
8.1.3. 
MRD Assessment and PET-CT Imaging 
Targeted next generation sequencing (NGS) will be used to assess minimal residual 
disease (MRD) status, utilizing a central testing lab. After the initial MRD sample 
collection during Screening, further MRD testing should first take place when a 
participant first achieves a confirmed response of VGPR, and every 6 months from the 
time of last sample collection until disease progression or suspected CR. In case of 
deepening response from VGPR to suspected CR (e.g. negative immunofixation by 
serum and urine, disappearance of any soft tissue plasmacytomas if present at Screening, 
normal FLC ratio for patients whose only measurable parameter at Screening is serum 
FLC), MRD testing should be performed at the time of achieving suspected CR and 
repeated every 6 months from  the time of last sample collection, until PD. Response 
evaluation will be performed according to the IMWG Uniform Response Criteria for 
Multiple Myeloma [Kumar, 2016]. For participants who are MRD negative by NGS (at 
10--5 sensitivity threshold), a PET-CT will be performed within 42 days (6 weeks) of 
confirming MRD negativity to assess for absence of disease on imaging. 
MRD samples could be analyzed once collected as long as date and time information is 
collected. 
8.2. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. Safety 
assessments include the following: 
• 
Complete physical examinations, including height (cm) and weight (kg) 
• 
Vital signs (blood pressure, body temperature, pulse rate) 
• 
Ocular exams 
• 
ECOG performance status 
• 
Clinical chemistry, hematology, and other laboratory tests (Table 19) 
• 
Serum beta-human chorionic gonadotropin (-HCG) pregnancy test for female 
participants of childbearing potential only  
• 
12-lead ECG at Screening. 
• 
Patient-Reported Outcome Version of Common Toxicity Criteria for Adverse 
Events (PRO-CTCAE, [Babb, 1998; Basch, 2014]): The PRO-CTCAE includes 
an item library of 124 items representing 78 symptomatic toxicities drawn from 
the CTCAE. PRO-CTCAE provides a systematic yet flexible tool for descriptive 
reporting of symptomatic treatment side effects in cancer clinical trials. In the 
present study, a subset of items selected from the PRO-CTCAE Version 1.0 
Item Library will be administered. 

 
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• 
Visual Functioning Questionnaire: The visual function questionnaire will 
include the Ocular Surface Disease Index (OSDI, [Schiffman, 2000]). 
8.2.1. 
Physical Examinations 
At screening, on dosing days, and at EoT Visit a full physical examination will include 
assessments of the head, eyes, ears, nose, throat, skin, thyroid, lungs, cardiovascular, 
neurological, abdomen (liver and spleen), lymph nodes, and extremities. Height (once at 
screening only) and weight must also be measured and recorded. 
8.2.2. 
ECOG Performance Status 
Participant performance status will be assessed at screening and then as specified in the 
SOA, using the Eastern Cooperative Oncology Group (ECOG) scale provided in Section 
10.6. 
8.2.3. 
Vital Signs 
Vital sign measurements must include systolic and diastolic blood pressure, temperature, 
and pulse rate. Vital signs must be measured after resting for at least 5 minutes. Vital 
signs must be measured more frequently if warranted by the clinical condition of the 
participant. On days where vital sign time points align with blood sampling time points, 
vital signs should be assessed prior to blood samples being drawn. On days where vital 
signs are measured multiple times, temperature does not need to be repeated unless 
clinically indicated. 
8.2.3.1. 
Vital Sign Measurement for Treatment Arm A 
For Treatment Arm A, vital signs are to be measured at the following time points at the 
time of first belantamab mafodotin infusion: 
• Within 30 minutes prior to Start of Infusion (SOI) 
• 15 mins after SOI (±10 min)  
• Within 15 min after End of Infusion (EOI)  
• At 1 hour (±10 min) after EOI  
On subsequent dosing days, vital signs must be assessed pre-dose (within 30 minutes 
prior to SOI) and within 15 min after EOI, and as clinically indicated. 
Vital signs should be assessed for bortezomib as clinically indicated. 
8.2.3.2. 
Vital Sign Measurement for Treatment Arm B 
For Treatment Arm B, vital signs are to be measured at the following time points at the 
time of first daratumumab administration: 
• Within 30 mins prior to Start of Infusion (SOI) 

 
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• At 30 mins, 2 hours, and 3 hours 30 mins after the start of the infusion (±10 mins) 
• Within 15 mins of EOI 
• 30 minutes, 1 hour, and 2 hours after EOI (±10 mins)  
On Cycle 1 Day 1, if daratumumab administration is split and given over Day 1 and 
Day 2, vital signs are to be measured on both Day 1 and Day 2 as per above time points. 
For all other daratumumab infusions, blood pressure will be measured within 30 mins 
prior to SOI and within 15 mins after EOI, and as clinically indicated. 
Vital signs should be assessed for bortezomib as clinically indicated. 
8.2.4. 
Electrocardiogram 
A 12-lead electrocardiogram (ECG) is obtained at screening as specified in the Schedule 
of Activities. The ECG machine should automatically calculate the heart rate and 
measure PR, QRS, QT, and QTc intervals according to Fridericia’s formula (QTcF). No 
further ECGs are required, but if obtained as part of medical care a 12-lead ECG should 
be performed by qualified personnel at the site after the participant has at least a 5-minute 
rest.  
Triplicate ECG should be performed if during treatment QTcF is >530 msec. 
Where triplicate ECGs are required, 3 individual ECG tracings should be obtained as 
closely as possible in succession, but no more than 2 minutes apart. The full set of 
triplicate ECGs should be completed in 4 minutes or less. 
Whenever vital signs, 12-lead electrocardiograms (ECGs), and blood draws are scheduled 
for the same nominal time, the 12-lead ECG should be performed first.  
8.2.5. 
Clinical Safety Laboratory Assessments 
Clinical laboratory tests to be performed are listed in Table 19. Refer to the SoA for the 
timing and frequency (Section 1.3). Details for the preparation and shipment of samples 
for central laboratory assessments will be provided in the SRM/Clinical Lab Manual. 
The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant 
abnormal laboratory findings are those which are not associated with the underlying 
disease, unless judged by the investigator to be more severe than expected for the 
participant's condition. 
All laboratory tests with values that are significantly abnormal during participation in the 
study or at least 70 days after the last dose of study treatment must be repeated until the 
values return to normal or baseline. 

 
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If such values do not return to normal within a period judged reasonable by the 
investigator, the etiology must be identified and the sponsor notified. 
8.2.6. 
Ophthalmic Assessments 
Study sites must establish a close collaboration with a qualified eye care specialist 
(Appendix 10) who will be responsible for assessing participants while they are on study 
and managing participants who develop corneal changes associated with belantamab 
mafodotin. Management of participants with corneal findings must be performed in close 
communication with the GSK Medical Monitor and the coordinating eye care specialist. 
Participants will be assessed by a qualified eye care specialist (Appendix 10) at 
screening/baseline in both arms. 
A full screening/baseline ophthalmic examination for all participants must include for 
both eyes (OU): 
1. Best corrected visual acuity. 
2. Documentation of manifest refraction and the method used to obtain best 
corrected visual acuity. 
3. Current glasses prescription (if applicable). 
4. Anterior segment (slit lamp) examination with focus on the cornea and lens, 
including fluorescein staining of the cornea 
5. Intraocular pressure measurement  
6. Dilated funduscopic exam. 
The on treatment and follow-up ophthalmic exam should be performed for both eyes 
(OU) as described below and in the SoA: 
1. Best corrected visual acuity. 
2. Documentation of manifest refraction and the method used to obtain best 
corrected visual acuity. 
3. Anterior segment (slit lamp) examination with focus on the cornea and lens, 
including fluorescein staining of the cornea 
4. Intraocular pressure measurement (if clinically indicated)  
5. Dilated funduscopic exam (if clinically indicated) 
The end of treatment and last follow-up ophthalmic exam, if required, should match the 
screening/baseline exam.  
Additional examinations should be performed at the discretion of the treating eye 
specialist.  

 
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8.2.6.1. 
Treatment Arm A 
Participants will be assessed by a qualified eye care specialist at screening/baseline and 
then Q3W prior to dosing up to the sixth dose of belantamab mafodotin (assessment 
window of up to 5 days prior to dosing, but all effort should be made to schedule as close 
to belantamab mafodotin dosing as possible). 
• 
If there are no significant ocular examinations findings, patient’s symptoms or 
vision changes at or prior to the time of the sixth dose exam, participants may 
have their ophthalmologic exams decreased to once every 3 months. 
• 
If a participant subsequently develops vision changes or other ocular symptoms, 
the participant should be promptly evaluated by a qualified eye care specialist. 
• 
In case of persistent ophthalmic exam findings, newly developed ocular 
symptoms or vision changes at the sixth dose exam, the participants will have 
further ophthalmologic exams, at least every cycle until resolution (to Grade 1 or 
baseline) or more frequently as clinically indicated by the qualified eye care 
specialist. 
If steroid eye drops are deemed medically necessary and prescribed, intraocular pressure 
must be monitored if used for >7 days. 
Participants with treatment-related ocular AEs at the End of Treatment Visit will be 
followed by the qualified eye care specialist (Appendix 10) at least every 3 months, for 
up to 12 months or until resolution (to Grade 1 or baseline), whichever comes first. These 
examinations are referred to as “follow-up visits”. 
8.2.6.2. 
Treatment Arm B 
Ocular exam may be performed up to 5 days prior to dosing. On treatment ocular exams 
to be performed at Cycle 6 and then decreased to every 6 months (4 week window) until 
and including eye exam at end of treatment. In case of persistent or newly developed 
ocular symptoms or vision changes, participants will have further ophthalmologic exams 
by a qualified eye care specialist (Appendix 10), as clinically indicated, until resolution 
(to Grade 1 or baseline). 
Participants who have treatment-related ocular AEs present at the end of treatment will 
continue to be followed by qualified eye care specialist at least every 3 months, for up to 
12 months or until resolution (to Grade 1 or baseline), whichever comes first. 
8.2.7. 
Patient-Reported Outcome Version of the Common Term Criteria 
for Adverse Events (PRO-CTCAE) 
The Patient-Reported Outcomes Version of the Common Terminology Criteria for 
Adverse Events (PRO-CTCAE) is a patient-reported outcome measure developed to 
evaluate symptomatic toxicity in patients on cancer clinical trials [Basch, 2014]. The 
PRO-CTCAE was designed to be used as a companion to the Common Terminology 
Criteria for Adverse Events (CTCAE), the standard lexicon for adverse event reporting in 
cancer trials. The PRO-CTCAE includes an item library of 124 items representing 78 

 
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symptomatic toxicities drawn from the CTCAE. PRO-CTCAE provides a systematic yet 
flexible tool for descriptive reporting of symptomatic treatment side effects in cancer 
clinical trials. In the present study, a selection of items from the PRO-CTCAE Version 
1.0 Item Library will be administered to participants (see SRM for further details). The 
PRO-CTCAE will be administered to participants in different regions based on the 
availability of translated versions. 
8.2.8. 
Pregnancy Testing (WOCBP Only) 
The need for a screening pregnancy test depends on whether a female participant is of 
childbearing potential or non-childbearing potential. 
Women of child-bearing potential (WOCBP) must have a negative highly sensitive serum 
pregnancy test within 72 hours of dosing on C1D1. Participants with positive pregnancy 
test result must be excluded from the study. Participants with negative pregnancy test 
result must agree to use a highly effective method of contraception (with a failure rate of 
<1% per year) during the study and for 4 months following the last dose of belantamab 
mafodotin (Arm A), 3 months from the last dose of daratumumab (Arm B), and 7 months 
from the last dose of bortezomib whichever is longest. 
Subsequent pregnancy testing on dosing days may be either by serum or urine testing. 
Each pregnancy test must be performed within 72 hours prior to dosing. 
8.3. 
Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Section 10.2. 
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study intervention or the 
study, or that caused the participant to discontinue the study intervention (Section 7).  
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All SAEs will be collected from the start of study intervention until at least 70 
days after discontinuing all study interventions, regardless of initiation of a new 
cancer therapy or transfer to hospice, at the time points specified in the SoA 
(Section 1.3). However, any SAEs assessed as related to study participation 
(e.g., study intervention, protocol-mandated procedures, invasive tests, or 
change in existing therapy) or related to a GSK product will be recorded from 
the time a participant consents to participate in the study up to and including any 
follow-up. 
• 
All AEs will be collected from the start of treatment until at least 70 days 
following discontinuation of study treatment regardless of initiation of a new 
cancer therapy or transfer to hospice at the time points specified in the SoA. 

 
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• 
Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the eCRF, not the AE section. 
• 
All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in Section 
10.2. The investigator will submit any updated SAE data to the sponsor within 
24 hours of it being available. 
• 
Investigators are not obligated to actively seek AEs or SAEs after the conclusion 
of the study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the 
study, and he/she considers the event to be reasonably related to the study 
intervention or study participation, the investigator must promptly notify the 
sponsor. 
 
8.3.2. 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.2. 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence.  
8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All AEs/SAEs, and non-serious AEs of special 
interest (as defined in Section 8.3.7), will be followed until the event is resolved, 
stabilized, otherwise explained, or the participant is lost to follow-up (as defined in 
Section 7.3). Further information on follow-up procedures is given in Section 10.2. 
8.3.4. 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the sponsor of an SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study intervention under clinical investigation are 
met.  
• 
The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study intervention 
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
Institutional Review Boards (IRB)/Independent Ethics Committees (IEC), and 
investigators. 
• 
Investigator safety reports must be prepared for Suspected Unexpected Serious 
Adverse Reactions according to local regulatory requirements and sponsor 
policy and forwarded to investigators as necessary. 

 
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• 
An investigator who receives an investigator safety report describing a SAE or 
other specific safety information (e.g., summary or listing of SAE) from the 
sponsor will review and then file it along with the IB and will notify the 
IRB/IEC, if appropriate according to local requirements. 
 
8.3.5. 
Pregnancy 
Details of all pregnancies in female participants will be collected after the start of study 
treatment and for 4 months following the last dose of belantamab mafodotin, or 7 months 
for bortezomib, whichever is longest. 
Details of pregnancies from female partners of male participants will be collected after 
the start of study treatment and for 6 months following the last dose of belantamab 
mafodotin or 4 months for bortezomib, whichever is longest. 
If a pregnancy is reported, the investigator must inform GSK within 24 hours of learning 
of the pregnancy and must follow the procedures outlined in Section 10.3. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, and ectopic pregnancy) are considered SAEs. 
8.3.6. 
Cardiovascular and Death Events 
The Death eCRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within 1 week 
of when the death is reported. 
For any cardiovascular events detailed in Section 10.2.3 (whether or not they are 
considered SAEs) and all deaths, specific Cardiovascular (CV) and Death sections of the 
eCRF will be required to be completed. These sections include questions regarding 
cardiovascular (including sudden cardiac death) and non-cardiovascular death.  
The CV eCRFs are presented as queries in response to reporting of certain CV MedDRA 
terms. The CV information should be recorded in the specific Cardiovascular section of 
the eCRF within 1 week of receipt of a CV event data query prompting its completion.  
Death due to the disease under study is to be recorded on the Death eCRF.  
8.3.7. 
Adverse Events of Special Interest 
Adverse events of special interest (AESI) for belantamab mafodotin are corneal events, 
thrombocytopenia and infusion-related reactions. Severity of all AESIs will be graded 
using National Cancer Institute-Common Toxicity Criteria for Adverse Events (CTCAE, 
v5.0). Guidelines for dose modifications and interruptions for management of common 
toxicities associated with the study treatment(s) are provided in Section 6.6. Dose 
modifications for belantamab mafodotin corneal events (Table 11) will be based on 
grading of corneal events according to the guidelines of Keratopathy Visual Acuity 
(KVA) Scale (Appendix 9, Table 30). 

 
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8.4. 
Treatment of Overdose 
GSK does not recommend a specific treatment for an overdose of belantamab mafodotin. 
In the event of an overdose of belantamab mafodotin, the investigator must: 
• 
Contact the GSK Medical Monitor immediately. 
• 
Monitor the participant closely for AEs, SAEs, and laboratory abnormalities 
until these have resolved, and belantamab mafodotin concentrations are 
predicted to be within the anticipated range in absence of the overdose. 
• 
Document the quantity of the excess dose as well as the duration of the 
overdosing in the eCRF. 
• 
Obtain an additional PK and serum sBCMA sample as soon as the overdose 
situation is recognized and contact the GSK medical monitor for further 
guidance with regards to additional sample collection (determined on a case-by-
case basis). 
• 
Decisions regarding dose interruptions or modifications will be made by the 
investigator in consultation with the Medical Monitor based on the clinical 
evaluation of the participant. 
There is no known specific antidote for bortezomib. In the event of an overdose of 
bortezomib, the participant’s vital signs should be monitored and appropriate supportive 
care given to maintain blood pressure (such as fluids, pressors, and/or inotropic agents) 
and body temperature [Velcade USPI, 2021; Velcade SmPC, 2020].  
There is no known specific antidote for daratumumab overdose. In the event of an 
overdose, the participant should be monitored for any signs or symptoms of adverse 
effects and appropriate symptomatic treatment should be instituted immediately 
[Darzalex USPI, 2019; Darzalex SmPC, 2019]. 
An overdose or prolonged use of dexamethasone may exaggerate glucocorticoid adverse 
effects. Treatment should be symptomatic and supportive with the dosage of 
dexamethasone being reduced or slowly withdrawn where possible. 
For further information, see the SRM for package inserts. 
8.5. 
Pharmacokinetics 
8.5.1. 
Belantamab Mafodotin Blood Sample Collection for 
Pharmacokinetics 
In Treatment Arm A, blood samples for PK analysis of belantamab mafodotin (ADC with 
or without total monoclonal antibody) and cys-mcMMAF will be collected at the time 
points indicated in the SoA, Table 20, and Table 21. Each PK sample must be collected 
as close as possible to the planned time relative to the dose administered to the participant 
on PK sampling days. The actual date and time of each blood sample collection will be 
recorded. 

 
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The first approximately 20% of participants in Treatment Arm A, as well as all 
participants from North East Asia receiving belantamab mafodotin, will undergo 
additional belantamab mafodotin PK sampling (Enhanced PK Cohort) according to the 
schedule in Table 20. For all remaining participants on Treatment Arm A, the samples 
will be collected as per the Standard PK Collection schedule in Table 21. For further 
details, see the SRM. 
Details on PK blood sample collection including blood volumes, processing, storage, and 
shipping procedures are provided in the SRM/Clinical Lab Manual. 
Soluble BCMA (sBCMA) samples should be collected at all PK time points (according to 
either the standard or enhanced schedule, see Section 8.9.1, Table 22 and Table 23). All 
PK, sBCMA, and ADA samples, once collected (regardless of dosing), will be analysed 
if the sample date and time have been recorded. 
Pharmacokinetic and accompanying sBCMA sample collection may be terminated when 
sufficient data have been collected. 
Table 20 
PK Schedule for Enhanced PK Collection (Treatment Arm A Only) 
Dose/Day1 
Timing 
Comments 
Dose1 Day1 
Pre-dose 
Within 30 min prior to Start of Infusion (SOI) 
End of Infusion (EOI) 
Within 30 min after EOI 
2 hours after SOI 
2 hours (15 min) after C1D1 SOI 
Dose 1 Day 1/Dose 1 
Day2 
24 hours after SOI on 
C1D1 
24h (2h) hours after Dose 1 SOI 
Dose 1 Day 4 
Prior to bortezomib 
administration 
72h (24h) hours after C1D1 SOI. If this coincided with a 
bortezomib administration day, PK sample should be taken 
prior to bortezomib administration. 
Dose 1 Day 8 to 
Day15 
1 sample on any one 
study day between 
C1D8 and C1D15 
Any time between D8 and D15. If this coincided with a 
bortezomib administration day, PK sample should be taken 
prior to bortezomib administration. 
Dose 2 Day 1 
Pre-dose 
Collect within 30 min prior to SOI  
If Cycle 2 belantamab mafodotin dose is delayed, 1 PK sample 
must be taken at Dose1 Day 22.  
EOI 
Within 30 min after EOI 
4th and 6th 
Belantamab 
Mafodotin dose 
Pre-dose AND 
EOI 
Within 30 min prior to SOI 
Within 30 min after EOI 
9th and 12th 
Belantamab 
Mafodotin dose 
Pre-dose 
 
Within 30 min prior to SOI 
 
Every 6 subsequent 
doses 
Pre-dose 
Within 30 min prior to SOI; for treatment beyond Dose 12, pre-
dose samples will be collected every 6 doses (Dose 18, Dose 
24, Dose 30 and so on, until the last sample at EOT). 
Note: C = Cycle; D = Day; SOI = Start of Infusion; EOI = End of Infusion; h = hour; sBCMA = soluble BCMA; EOT = 
End of Treatment.  
1. This PK sample is tied to the DOSE of belantamab mafodotin. This may not correspond to the CYCLE of treatment 
e.g., in the event that belantamab mafodotin is held whilst Vd continues. 
 
Participants on Treatment Arm A not requested to undergo Enhanced PK sampling 
should follow the schedule for Standard PK assessments as laid out in Table 21. 

 
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Table 21 
PK Schedule for Standard PK Collection (Treatment Arm A Only) 
Dose/Day1 
Timing 
Comments 
Dose 1 Day 1 
Pre-dose 
To be collected within 30 min prior to SOI 
EOI 
Within 30 min after EOI 
Dose 1 Day 1/Dose 1 
Day2 
24 hours after 
SOI on C1D1 
24 (2 hours) hours after Dose 1 SOI 
Dose 2 Day 1 
Pre-dose 
Collect within 30 min prior to SOI.  
If Cycle 2 belantamab mafodotin dose is delayed, 1 PK sample must be 
taken at Dose 1 Day 22. 
EOI 
Within 30 min after EOI 
4th, and 6th 
belantamab 
mafodotin dose 
Pre-dose and 
EOI 
Within 30 min prior to SOI and after EOI (0-30 min) 
9th and 12th 
belantamab 
mafodotin dose 
Pre-dose 
Within 30 min prior to SOI 
Every 6 subsequent 
doses  
Pre-dose 
Within 30 min prior to SOI; for treatment beyond Dose 12, pre-dose 
samples will be collected every 6 doses (Dose 18, Dose 24, Dose 30 
and so on, until the last PK sample at EOT). 
Note: C = Cycle; D = Day; SOI = Start of Infusion; EOI = End of Infusion; h = hour; sBCMA = soluble BCMA; EOT = 
End of Treatment.  
1. This PK sample is tied to the DOSE of belantamab mafodotin. This may not correspond to the CYCLE of treatment 
e.g., in the event that belantamab mafodotin is held whilst Vd continues. 
8.5.2. 
Belantamab Mafodotin PK Sample Analysis 
Plasma analysis will be performed under the control of GSK, the details of which will be 
included in the Lab Manual. Concentrations of belantamab mafodotin (ADC with or 
without total monoclonal antibody) and cys-mcMMAF will be determined in plasma 
samples using the currently approved bioanalytical methodology. Raw data will be 
archived at the bioanalytical site (detailed in the Lab Manual). 
Once the plasma has been analyzed for belantamab mafodotin (ADC with or without total 
monoclonal antibody) and cys-mcMMAF, any remaining plasma may be analyzed for 
other compound-related metabolites and the results reported under a separate GSK 
protocol. 
8.5.3. 
Daratumumab and Bortezomib 
No PK sampling or analysis is required for bortezomib, dexamethasone, or daratumumab 
in Arms A and B. For daratumumab, no anti-daratumumab antibody sampling or analysis 
is required. 
8.6. 
Belantamab Mafodotin Immunogenicity 
Serum samples for the analysis of anti-belantamab mafodotin antibodies will be collected 
prior to each belantamab mafodotin infusion (at Doses 1, 2, 4, 6, 9 and 12 at the same 
time as the pre-infusion belantamab mafodotin PK samples are taken); for treatment 
beyond 12 doses, collect samples for ADA analysis prior to each infusion every 6th dose 

 
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of belantamab mafodotin (Dose 18, Dose 24, Dose 30, and so on, until PD). A final ADA 
sample will be drawn at the EOT visit. These samples will be tested by the sponsor or 
sponsor’s designee.  
Anti-belantamab mafodotin antibody samples will be tested for anti-belantamab 
mafodotin antibodies using a tiered-testing scheme consisting of validated screening, 
confirmation, and titration assays. Briefly, all samples will be tested in the screening 
assay. Samples that screen positive are considered potentially positive and will be tested 
for specificity in a confirmation assay. Finally, titer values will be obtained for confirmed 
positive samples using a titration assay. The sample results (e.g., positive or negative) 
and titer values (positive samples only) will be reported. Samples that test positive for 
anti-belantamab mafodotin antibodies may be further characterized in a validated 
neutralizing antibody assay to determine the neutralizing activity of the antibodies.  
The detection and characterization of antibodies to belantamab mafodotin will be 
performed using validated assays. The anti-belantamab mafodotin antibody assay was 
designed to detect antibodies to belantamab mafodotin, the unconjugated monoclonal 
antibody and the linker-payload portion of the belantamab mafodotin. Anti-belantamab 
mafodotin antibody samples will be disposed 3 months after final approved results are 
provided to the Clinical Study Team or its designee or upon documented study 
termination. 
ADA sample collection may be reduced or terminated when sufficient data have been 
collected. 
8.7. 
Pharmacodynamics 
See Section 8.9 for details of biomarkers to be collected. 
8.8. 
Genetics 
A 6 mL blood sample for DNA isolation will be collected from participants who have 
consented to participate in the optional genetics analysis component of the study. 
Participation in this part of the study is optional and all enrolled participants will be given 
the opportunity to contribute samples. Participation may be declined without effect on 
medical care during the clinical study. A separate consent signature is required for 
participation in genetic research. 
In the event of DNA extraction failure, a replacement genetic blood sample may be 
requested from the participant. Signed informed consent will be required to obtain a 
replacement sample unless it was included in the original consent. 
Information regarding genetic research is included in Section 10.5. In approving the 
clinical protocol, the IEC/IRB and, where required, the applicable regulatory agency, are 
also approving the genetic research described in Section 10.5 unless otherwise indicated. 
Where required by regulatory authorities, approval of the genetic assessments can occur 
after approval is obtained for the rest of the study. In that case, written approval will 
indicate that approval of the genetic assessments is being deferred and the study, except 

 
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for genetic assessments, can be initiated. If genetic assessments are not approved, they 
will not be conducted. 
8.9. 
Biomarkers 
Biomarker research is part of this study and will involve peripheral blood, bone marrow, 
and tumor biopsies. Soluble BCMA (sBCMA), BCMA expression in tumor cells, and 
circulating plasma cell-free DNA (cfDNA) analyses will be performed and the 
relationship of these biomarkers relative to response to belantamab mafodotin will be 
assessed. Additionally, any blood, serum, plasma, and bone marrow samples collected 
during this study may be used to measure novel biomarkers to identify factors associated 
with the biological and clinical responses to belantamab mafodotin. If relevant, this 
approach may be extended to include the identification of biomarkers associated with 
AEs. Unless stated otherwise, these investigations may be performed irrespective of 
whether a response to belantamab mafodotin is observed. The novel biomarkers may 
involve DNA analysis, RNA analysis, and/or protein analysis.  
Samples will be collected at the time points indicated in the SoA. Biomarker samples, 
including bone marrows and sBCMA, could be analyzed as long as date and time 
information is collected.  
The sample collection strategy may be adjusted on the basis of emerging data from this 
study or other studies involving belantamab mafodotin in order to ensure optimal 
evaluation of any potential biomarkers. If biomarkers potentially predictive of response 
or associated with AEs are identified, samples may be used for the development of 
validated assays and/or diagnostic tests. Additionally, novel biomarkers may also be 
incorporated, as data warrant. These analyses may include but not be limited to: 
 
8.9.1. 
Soluble BCMA  
The BCMA receptor undergoes gamma-secretase mediated cleavage, leading to release 
of the BCMA extracellular domain as soluble BCMA (sBCMA) into circulation [Laurent, 
2015]. 
sBCMA will be measured in both Arm A and Arm B. 
For Arm A, sBCMA samples should be collected at all PK time points (according to 
either the standard or enhanced schedules). See Table 22 and Table 23 below. 
sBCMA samples will also be taken in Arm B, as described in Table 24 below. 
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Serum analysis for sBCMA will be performed under control of GSK (further details are 
included in the SRM). Raw data will be archived at the bioanalytical site (detailed in the 
SRM). 
Details on sBCMA blood sample collection including blood volumes, processing, 
storage, and shipping procedures are provided in the SRM. 
Table 22 
Treatment Arm A sBCMA Blood Collection (Enhanced PK Cohort) 
Dose/Day1 
Timing 
Comments 
Screening 
Screening 
Anytime during screening  
Dose1 Day11 
Pre-dose 
Within 30 min prior to Start of Infusion (SOI) 
End of Infusion (EOI) 
Within 30 min after EOI 
2 hours after SOI 
2 hours (15 min) after C1D1 SOI 
Dose 1 Day 1/Dose 1 
Day21 
24 hours after SOI on 
C1D1 
24h (2h) hours after Dose 1 SOI 
Dose 1 Day 41 
Prior to bortezomib 
administration 
72h (24h) hours after C1D1 SOI. If this coincided with a 
bortezomib administration day, sample should be taken prior to 
bortezomib administration 
Dose 1 Day 8 to 
Day151 
1 sample on any one 
study day between 
C1D8 and C1D15 
Any time between D8 and D15. If this coincided with a 
bortezomib administration day, sample should be taken prior to 
bortezomib administration 
Dose 2 Day 11 
Pre-dose 
Collect within 30 min prior to SOI  
If Cycle 2 belantamab mafodotin dose is delayed, 1 sample 
must be taken at Dose1 Day 22 
EOI 
Within 30 min after EOI 
4th and 6th 
Belantamab 
Mafodotin dose1 
Pre-dose AND 
EOI 
Within 30 min prior to SOI 
Within 30 min after EOI 
9th and 12th 
Belantamab 
Mafodotin dose1 
Pre-dose 
 
Within 30 min prior to SOI 
 
Every 6 subsequent 
doses1 
Pre-dose 
Within 30 min prior to SOI; for treatment beyond Dose 12, pre-
dose samples will be collected every 6 doses (Dose 18, Dose 
24, Dose 30 and so on, until the last sample at EOT) 
EOT 
EOT visit 
Anytime 
C = Cycle; D = Day; SOI = Start of Infusion; EOI = End of Infusion; h = hour; sBCMA = soluble BCMA; EOT = End of 
Treatment. 
1. This PD sample is tied to the DOSE of belantamab mafodotin. This may not correspond to the CYCLE of treatment 
e.g., in the event that belantamab mafodotin is held whilst Vd continues. 
 

 
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Table 23 
Treatment Arm A sBCMA Blood Collection (Standard PK Cohort) 
Dose/Day1 
Timing 
Comments 
Screening 
Screening 
Anytime during screening 
Dose 1 Day 11 
Pre-dose 
Within 30 min prior to SOI 
EOI 
Within 30 min after EOI 
Dose 1 Day 1/Dose 1 
Day21 
24 hours after SOI on 
C1D1 
24 (2 hours) hours after Dose 1 SOI 
Dose 2 Day 11 
Pre-dose 
Collect within 30 min prior to SOI.  
If Cycle 2 belantamab mafodotin dose is delayed, 1 sample 
must be taken at Dose 1 Day 22 
EOI 
Within 30 min after EOI 
4th and 6th 
belantamab 
mafodotin dose1 
Pre-dose AND EOI 
Within 30 min prior to SOI 
Within 30 min after EOI 
9th and 12th 
belantamab 
mafodotin dose1 
Pre-dose 
Within 30 min prior to SOI 
Every 6 subsequent 
doses1 
Pre-dose 
Within 30 min prior to SOI; for treatment beyond Dose 12, pre-
dose samples will be collected every 6 doses (Dose 18, Dose 
24, Dose 30 and so on, until the last PD sample at EOT) 
EOT 
EOT visit 
Anytime 
Note: C = Cycle; D = Day; SOI = Start of Infusion; EOI = End of Infusion; h = hour; sBCMA = soluble BCMA; EOT = 
End of Treatment.  
1 This PD sample is tied to the DOSE of belantamab mafodotin. This may not correspond to the CYCLE of treatment 
e.g., in the event that belantamab mafodotin is held whilst Vd continues. 
 
Table 24 
Treatment Arm B sBCMA Blood Collection  
Dose/Day1 
Timing 
Comments 
Screening 
Screening  
Anytime during screening  
Dose1 Day11 
Pre-dose 
Within 30 min prior to Start of Infusion (SOI) 
End of Infusion (EOI) 
Within 30 min after EOI 
Dose 1 Day 41 
Prior to bortezomib 
administration 
72h (24h) hours after C1D1 SOI. If this coincided with a 
bortezomib administration day, sample should be taken prior 
to bortezomib administration 
Dose 1 Day 8 to 
Day151 
1 sample on any one 
study day between 
C1D8 and C1D15 
Anytime between D8 and D15. If this coincided with a 
bortezomib administration day, sample should be taken prior 
to bortezomib administration 
EOT 
EOT visit 
Anytime 
C = Cycle; D = Day; SOI = Start of Infusion; EOI = End of Infusion; h = hour; sBCMA = soluble BCMA; EOT = End of 
Treatment 
1. This PD sample is tied to the DOSE of daratumumab. This may not correspond to the CYCLE of treatment e.g., in 
the event that daratumumab is held whilst Vd continues. On Cycle 1 Day 1 first daratumumab dosing only, if 
daratumumab administration is split and given over Day 1 and Day 2, then the sBCMA sample will need to be 
collected within 30 min after EOI on Day 2 only. 
 
8.9.2. 
Tumor-related Biomarkers 
While BCMA expression is present in all multiple myeloma cells, there is some cell by 
cell variability and also differences in membranous and cytosolic localization patterns. 
Therefore, it is important to determine if there is any association between the expression 

 
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levels of BCMA on multiple myeloma cells and clinical responses. Bone marrow samples 
will be collected during this study at the time points indicated in the SoA.  
An optional bone marrow and/or tissue sample (BM aspirate and/or biopsy, or fresh 
tissue (tissue block) from extramedullary tumor) may be collected at time of disease 
progression (PD) from participants who have signed a separate consent for this sample. 
Participation in this part of the study is optional and all enrolled participants will be given 
the opportunity to contribute samples. Participation may be declined without effect on 
medical care during the clinical study.  
BCMA expression analysis to be performed preferably on a bone marrow biopsy sample, 
any remaining aspirate and/or biopsy sample will be used for biomarker research (which 
may include immune cell characterization and/or profiling and/or DNA/RNA analyses).  
 
8.9.3. 
Circulating Cell-Free DNA (cfDNA) Analysis 
Tumor specific circulating nucleic acid levels detected in plasma or serum have been 
found to correlate with increasing tumor burden and decline following therapy. cfDNA in 
cancer patients can harbor many genetic alterations (mutations, microsatellite alterations, 
aberrant methylation), which are generally consistent with the tumor. Tumor-specific 
circulating cfDNA has the potential to be a useful biomarker of therapeutic response as 
well as offer a less invasive blood-based technique for identifying and selecting patients 
for certain treatments. Given this promise, cfDNA will be explored to determine if 
mutations can be identified and correlate to response or resistance to treatment. This 
analysis may also explore correlating increasing cfDNA levels with increasing tumour 
burden.  
8.10. 
Health-Related Quality of Life 
Five health-related quality-of-life (HRQoL) assessments will be performed in this study. 
The questionnaires will be administered to participants in different regions based on the 
availability of translated versions. More details about all participant questionnaires can be 
found in the SRM.   
All participants will complete the self-administered version of the PRO questionnaires 
unless their vision prevents them from being able to complete the questionnaire on their 
own. Participants who are not able to complete the questionnaire on their own and require 
assistance should use an interviewer-administered format. If the interviewer-administered 
format is used, it should be read to the participant’s verbatim, and participant responses 
should be recorded directly without any interpretation. For any additional assessments 
conducted via telephone (either during participation in the Treatment period or during 
Follow-up), the interviewer-administered format should be used. The questionnaires will 
be administered to participants in different regions based on the availability of translated 
versions. 
PRO questionnaires should be completed by participants at the start of study visits before 
receiving any results and before discussing their health status with the study staff. 

 
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8.10.1. 
European Organization for Research and Treatment of Cancer 
Quality of Life Questionnaire 30-item Core module (EORTC QLQ-
C30) 
The EORTC QLQ-C30 is a 30-item questionnaire containing both single- and multi-item 
measures [Aaronson, 1993]. These include 5 functional scales (Physical, Role, Cognitive, 
Emotional, and Social Functioning), 3 symptom scales (Fatigue, Pain, and 
Nausea/Vomiting), a Global Health Status/QoL scale, and 6 single items (Constipation, 
Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). Scores for each 
scale and single-item measure are averaged and transformed linearly to a score ranging 
from 0–100. A high score for functional scales and for Global Health Status/QoL 
represent better functioning ability or HRQoL, whereas a high score for symptom scales 
and single items represents significant symptomatology [Proskorovsky, 2014]. 
8.10.2. 
European Organization for Research and Treatment of Cancer 
Item Library 52 (disease symptoms domain from the EORTC 
Quality of Life Questionnaire 20-item Multiple Myeloma module 
(EORTC QLQ-MY20) 
The EORTC QLQ-MY20 is a supplement to the QLQ-C30 instrument used in patients 
with multiple myeloma [Aaronson, 1993; Cocks, 2007]. Only the Disease Symptoms 
domain of the QLQ-MY20 will be administered, which includes bone aches or pain, back 
pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity. The 
disease symptom domain of the EORTC QLQ-MY20 will be referred to as the EORTC 
IL52. As with the QLQ-C30, QLQ-MY20 domain scores are averaged and transformed 
linearly to a score ranging from 0–100. A high score for Disease Symptoms represents a 
high level of symptomatology or problems [Proskorovsky, 2014]. 
8.10.3. 
EuroQol Questionnaire (EQ-5D-3L) 
The EQ-5D-3L is a standardised instrument for use as a measure of health utility. It is 
designed for self-completion or interview administration and is cognitively simple, taking 
only a few minutes to complete.  
The EQ-5D-3L self-assessment questionnaire has 2 parts. The first part consists of 5 
items covering 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression). Each dimension is measured by a 3-point Likert scale (no problems, 
some or moderate problems, and unable or extreme problems). Respondents are asked to 
choose one level that reflects their "own health state today" for each of the 5 dimensions. 
Respondents can be then classified into 1 of 243 distinct health states. The second part is 
a 20-cm visual analogue scale (EQ-VAS) that has endpoints labelled "best imaginable 
health state" and "worst imaginable health state" anchored at 100 and 0, respectively. 
Respondents are asked to indicate how they rate their own health by drawing a line from 
an anchor box to that point on the EQ-VAS which best represents their own health on that 
day. EQ-5D-3L health states are converted to a single summary index by applying a 
formula that essentially attaches weights to each of the levels in each dimension. The 
formula is based on the valuation of EQ-5D health states from general population 
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8.10.4. 
Functional Assessment of Cancer Therapy – General Population 
(FACT-GP5) 
The FACT-G (now in Version 4) is a 27-item compilation of general questions divided 
into 4 primary QoL domains:  Physical Well-Being, Social/Family Well-Being, 
Emotional Well-Being, and Functional Well-Being [Cella, 1993]. It is considered 
appropriate for use with participants with any form of cancer, and it has also been used 
and validated in other chronic illness condition (for example, HIV/AIDS and multiple 
sclerosis) and in the general population (using a slightly modified version). 
The FACT GP5 item is a single item from the FACT-G, which assesses how bothersome 
the side effects of treatment are for cancer patients. The recall period is the past 7 days, 
and the item has a 5-category response scale ranging from “0=Not at all” to “4=Very 
much”. This item is being included to assess the overall tolerability of treatment from the 
participant’s perspective. 
8.10.5. 
Patient Global Impression Items 
The Patient Global Impression of Severity (PGIS) assesses global impression of 
symptoms severity at baseline and subsequent timepoints. The second question, the 
Patient Global Impression of Change (PGIC) serves to rate the global change in 
symptoms at subsequent time points. In addition to evaluating symptom severity and 
change, these questions serve as anchors to establish thresholds of clinically meaningful 
change for the questionnaires in the study [Guy, 1976]. 
8.11. 
Visual Function Questionnaires 
The impact of potential ocular toxicity on function and health-related quality of life will 
be assessed with the use of the Ocular Surface Disease Index (OSDI). The OSDI is a 12-
item questionnaire designed to assess both the frequency of dry eye symptoms and their 
impact on vision-related functioning [Dougherty, 2011; Schiffman, 2000]. The OSDI has 
demonstrated good reliability, validity, sensitivity, and specificity, and can be used as a 
complement to other clinical and subjective measures of dry eye disease by providing a 
quantifiable assessment of dry eye symptom frequency and the impact of these symptoms 
on vision-related functioning. The OSDI will be completed by the participants at the 
times shown in the Schedule of Activities. 
8.12. 
Non-protocol Specified Health Care Resource Utilization 
Non-protocol specified Healthcare Resource Utilization (HRU) will be assessed in this 
study and reported by participants to study staff at each visit. Parameters to be measured 
include: 
• Number of office/outpatient/hospital clinic visits by specialty. 
• Number of emergency room/urgent care facility visits. 
• Number and duration of in-patient hospitalizations (total nights, including 
duration by wards [intensive care unit vs. general ward]). 
The data collected may be used to conduct exploratory economic analyses. 

 
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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
Primary PFS endpoint 
The following primary efficacy hypothesis will be tested, comparing the distribution of 
PFS between the 2 treatment groups: 
𝐻0: 𝜃≥1              𝑉𝑆.         𝐻1: 𝜃< 1 
where, 𝜃 is the PFS HR (belantamab mafodotin/bor/dex vs. daratumumab/bor/dex arm). 
 
Key secondary Overall Survival endpoint 
A key secondary OS analysis will be the comparison of the distribution of OS between 
the treatment groups. The following hypothesis may be tested: 
 
𝐻0: 𝜃1 ≥1              𝑉𝑆.         𝐻1: 𝜃1 < 1 
where, 𝜃1 is the OS HR (belantamab mafodotin/bor/dex vs. daratumumab/bor/dex arm). 
 
Key secondary Duration of Response endpoint 
The following key secondary hypotheses may be tested: 
𝐻0: 𝜇1 −𝜇0 ≤0              𝑉𝑆.         𝐻1: 𝜇1 −𝜇0 > 0 
where, 𝜇1 is the restricted mean duration of response (RMDOR) for the belantamab mafodotin/bor/dex arm and 𝜇0 is  
the RMDOR for the daratumumab/bor/dex arm. 
 
Key secondary Minimal Residual Disease Negativity endpoint  
A key secondary objective of the study is to compare the proportion of participants with 
MRD negativity, as assessed by NGS with a 10-5 sensitivity between the 2 treatment 
groups. The following statistical hypotheses will be tested: 
H0: P1 ≤ P0     VS. 
H1: P1 > P0 
where, 
P0 = proportion of participants with MRD negativity Arm B (daratumumab/bor/dex) 
P1 = proportion of participants with MRD negativity Arm A (belantamab mafodotin/bor/dex). 
 
 

 
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9.2. 
Multiple Comparisons and Multiplicity 
The objective of the study to compare the efficacy of Treatment A versus Treatment B 
and will consist of evaluating one primary and three key secondary endpoints (OS, DoR 
and MRD Negativity). The analyses will be performed as defined in Section 9.6.4. The 
study will provide multiplicity control for multiple hypotheses as well as interim analyses 
(planned interim analyses are defined in Section 9.6.2). The global family-wise error rate 
(FWER) is strongly controlled at 2.5% (one-sided). 
Evaluation of primary and key secondary endpoints will be structured in terms of two 
family of hypotheses. The first family will be based on the primary endpoint PFS, and the 
second family will be based on the three key secondary endpoints OS, DoR, and MRD 
Negativity. Testing of the second family of hypotheses is conditional on the successful 
rejection of the null hypothesis for the first family. If successful, the full alpha will be 
propagated to the second family of hypotheses. For the second family, a weighted 
Bonferroni procedure will be applied across OS and DoR. Alpha will be split between the 
endpoints, with a larger proportion assigned to OS initially. Testing of MRD will be 
conditional on the successful rejection of the null hypothesis for OS, aligned with a step-
down (or hierarchical) testing procedure [Bretz, 2009; Li, 2017]. Details regarding alpha 
allocation and propagation will be defined in the SAP. 
The primary PFS endpoint will be evaluated at an interim analysis (IA1) and at a primary 
PFS analysis / Interim Analysis 2  (IA2). The PFS analysis is based on using a Lan-
DeMets (O’Brien-Fleming) alpha spending function to define an efficacy boundary 
[Lan, 1983] 
. The amount of alpha allocated to 
the interim and primary PFS analyses is given in Table 28. The efficacy boundaries will 
be adjusted based on the actual number of PFS events observed at the time of analysis.  
OS will be tested across 4 planned analyses; IA1, Primary PFS analysis/IA2, IA3 and the 
final analysis. The Lan DeMet approach that approximates the O’Brien and Fleming 
spending function [Lan, 1983] will be used. The efficacy boundaries will be adjusted 
based on the actual number of OS events observed at the time of analysis. Additional 
analyses of OS may be performed upon requests or to provide updated data to the health 
authorities. The details of these analyses including the associated alpha-adjustment, if 
any, will be described in the SAP. 
Further details regarding the multiplicity strategy will be provided in the Statistical 
Analysis Plan (SAP). 
9.3. 
Sample Size Determination 
Primary Endpoint: PFS 
Based on data from the CASTOR study, the median PFS in Treatment Arm B is expected 
to be approximately 16.7 months [Spencer, 2018]. It is expected that treatment with 
belantamab mafodotin in combination with bor/dex will lead to a 
 
 
 
. 
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The primary PFS analysis will be conducted after observing approximately 
PFS 
events. With
 events, the study has a power of 
 
 
This calculation assumes participants are randomized to the two treatment arms in a 1:1 
randomization ratio. Assuming that a total of 478 participants will be randomized in a 1:1 
ratio to Arm A or Arm B and a uniform enrollment rate of
participants per month, 
enrollment will continue for approximately 16 months. It is estimated that the targeted 
PFS events will be observed approximately
months from the time when the first 
participant is randomized under H1, assuming an annual dropout rate of %. These 
calculations were conducted using East 6.4. 
There will be a
% global enrollment cap on North East Asia Countries. If the number 
of participants required by local regulatory agencies are not recruited within the planned 
recruitment target, enrollment may continue in separate cohorts until the country 
enrolment requirements, as required by local regulatory bodies, have been reached. 
Additional participants that are enrolled in separate cohorts will not be included in the 
analysis portion of the study planned for the marketing application, which is based on 
approximately
events. However, these additional participants will be included in 
country-specific supplemental analyses, requested by the applicable regulatory authorities 
concerned, as detailed in the country-specific SAP.  
Japan Expansion cohort: 
Once the enrollment into the global study is completed, recruitment into the Japan 
expansion cohort will continue in Japan, to enroll a total of
apanese participants, 
including any Japanese participants enrolled in the global study. These additional 
participants in the expansion cohort will be randomized in a 1:1 ratio to Arm A or Arm B 
using a separate randomization list. These additional participants in the expansion cohort 
will not be included in the statistical analyses of the global study. 
The sample size of Japan expansion cohort is based on the probability of obtaining a 
consistent result between the Japan expansion cohort population and overall population 
based on PFS. Given the expected small number of Japanese participants in the global
study, additional recruitment will continue into the Japan expansion cohort to achieve
dosed Japanese subjects in total. In the case of all 
patients are recruited in the Japan 
expansion cohort, the additional analysis of the Japan expansion cohort population will 
be conducted when approximately
PFS events have been documented from
Japanese subjects, and would provide 
 
 as the global study in PFS 
(expected around 
months from the date of the first Japanese participant randomized in 
the study under the alternative hypothesis assuming an accrual period of 16 months with 
participants uniformly enrolled). If required by local regulatory agency, interim analyses 
may be conducted before approximately
PFS events have been documented in the 
Japan expansion cohort. If PFS does not demonstrate statistical significance at IA1, the 
analysis for Japan expansion cohort will not be conducted until the primary PFS analysis, 
even if
PFS events have been observed. 
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The PFS is the primary efficacy endpoint and the additional efficacy analyses will be 
performed for Intent-to-treat (ITT)-Japan population. Further details will be provided in 
the Japan-specific SAP. 
 
9.4. 
Populations for Analyses 
For purposes of analysis, the following populations are defined: 
Population 
Description 
All Screened  
The All Screened Population will consist of all participants who sign the ICF to 
participate in the clinical trial. Participants in this population will be used for 
screen failure summary. 
Intent-to-Treat (ITT) 
ITT Population will consist of all randomized participants whether or not 
randomized treatment was administered. This population will be based on the 
treatment to which the participant was randomized and will be the primary 
population for the analysis of efficacy data. Any participant who receives a 
treatment randomization number will be considered to have been randomized. 
Modified ITT 
Participants who met all criteria below will be included: 
• 
Have received at least 1 line of prior therapy 
• 
With measurable disease at baseline  
• 
Randomized and received at least 1 dose of planned study treatment 
o 
Patient randomized to the belantamab mafodotin arm that received 
daratumumab will be excluded and vice versa  
o 
Patient randomized but never treated will be excluded 
Safety 
All randomized participants who take at least 1 dose of study intervention. 
Participants will be analyzed according to the intervention they actually 
received. 
Pharmacokinetic 
The Pharmacokinetic Population will consist of those participants in the Safety 
Population from whom at least 1 PK sample has been obtained and analyzed. 
This population will be the primary population for PK analyses. 
9.5. 
Statistical Analyses 
9.5.1. 
Efficacy Analyses 
Analysis of efficacy endpoints will be based on assessments determined by an IRC with 
the ITT population unless otherwise specified. Sensitivity analyses will be based on 
investigator-assessed responses. The analytical methods planned for each endpoint are 
described in Table 25. 
Stratification factors used for the stratified analyses include number of prior lines of 
therapy (1 vs 2/3 vs ≥4), prior bortezomib (yes vs no) and the revised International 
Staging System at screening (R-ISS I vs II/III). 
Appropriate subgroup analyses may be performed if data permits, e.g., the primary 
endpoint PFS may be analyzed by age (<65 years, ≥65 years), gender (Female, Male), 

 
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ethnicity (Hispanic, non-Hispanic) and race groups (American Indian or Alaskan Native, 
Asian, Black, Native Hawaiian or Other Pacific Islander, White, Mixed Race), region 
(North America, Europe, North East Asia, [consisting of Japan, China and Republic of 
Korea], etc.), prior anti-myeloma therapy and other baseline characteristics. 
Table 25 
Statistical Analytical Methods: Efficacy 
Endpoint 
Statistical Analysis Methods 
Primary 
PFS is the primary endpoint of this study; it is defined as the time from randomization until the 
earliest date of PD, determined by an IRC, according to IMWG criteria [Kumar, 2016], or death 
due to any cause. Determination of dates for PFS event and dates for censoring is described in 
Section 10.11. 
Final PFS (primary efficacy) analysis will be conducted at the time of observing approximately 
PFS events. The distribution of PFS for each treatment arm will be estimated using the 
Kaplan-Meier method. The median, 25th and 75th percentiles of PFS will be estimated and 
corresponding 95% confidence intervals will be estimated using the Brookmeyer-Crowley 
method [Brookmeyer, 1982]. The proportional hazard assumption will be checked through the 
Kaplan-Meier plot, log(-log(survival) against log (survival time) plot, Schoenfeld residuals, and 
evaluation of time dependency of HR by adding an interaction term of time by treatment in the 
Cox proportional hazard model. The distribution of PFS will be compared between the 2 
treatment arms using log-rank test stratified by randomization factors used for randomization. A 
one-sided p-value will be produced. HR and corresponding two-sided 95% CI will be estimated 
from Cox proportional hazard model stratified by randomization factors with treatment arm as 
the sole explanatory variable. If the proportional hazard assumption does not hold, Restricted 
Mean Survival Time (RMST) may be conducted in addition as appropriate. 
Sensitivity analyses will be conducted using alternative PFS censoring rules as described in 
Section 10.11 and using investigator-assessed responses and dates. Subgroup PFS analysis 
by randomization factors will be conducted at PFS analysis. 
Key Secondary 
OS, defined as the interval of time from randomization to the date of death due to any cause. 
Participants who are alive will be censored at the date of last contact or last known alive. 
OS analysis will be conducted at planned analyses using similar approach as for the PFS 
analysis (i.e. Kaplan-Meier estimates, stratified log-rank test, Cox proportional hazards model 
stratified by randomization factors, and examination of non-proportional hazards effect). 
The hypothesis testing and boundary crossing decision of the key secondary endpoint OS will 
be based on ITT population. 
Analyses of OS may also be performed based on mITT population. The analyses will only 
include Kaplan-Meier estimates, Cox proportional hazards model stratified by randomization 
factors. Details are provided in the SAP. 
Subgroup OS analysis by randomization factors will be conducted at primary PFS analysis 
based on ITT population. Details are provided in the SAP. 
DoR is defined as the time from first documented evidence of PR or better until progressive 
disease (PD) or death due to any cause. For the primary analysis of DoR, all participants will be 
included in the analysis regardless of response status, to enable a valid statistical comparison 
between the two arms. Response will be determined by an IRC according to IMWG criteria 
[Kumar, 2016]. DoR will be analyzed based on the restricted mean DoR (RMDOR) using a non-
parametric approach (Huang, 2022). Using this approach, non-responders will have an 
observed DoR of zero. Comparison of RMDOR between the two treatment arms will be based 
on a one-sided Z test. The RMDOR and the corresponding two-sided 95% confidence interval 
will be calculated for each arm. The difference in the RMDOR and the associated one-sided p-
value will be provided. 
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Endpoint 
Statistical Analysis Methods 
The hypothesis testing of the key secondary endpoint DoR will be based on the ITT 
populations. Subgroup DoR analyses by randomization factors may be conducted at primary 
PFS analysis based on ITT population. Details are provided in the SAP. 
Sensitivity analysis will be conducted using investigator-assessed responses. 
A supplementary analysis will be conducted based on a conventional DoR analysis, where DoR 
will be defined as the time from first documented evidence of PR or better until the earliest date 
of disease progression (PD), or death due to any cause, among participants who achieve a 
response (i.e., confirmed PR or better) as determined by an IRC, according to IMWG criteria 
[Kumar, 2016]. Responders without disease progression will be censored at the censoring time 
point for TTP. Distribution of DoR will be summarized using the Kaplan-Meier method by 
treatment arm. The median, 25th and 75th percentiles of DoR will be estimated and 
corresponding 95% confidence intervals will be estimated using the Brookmeyer-Crowley 
method [Brookmeyer, 1982]. An additional analysis may be conducted for conventional DoR 
using investigator-assessed responses. 
 
MRD negativity rate, defined as the percentage of participants who achieve MRD negative 
status (as assessed by NGS at 10-5 threshold) at least once during the time of confirmed CR or 
better response based on IRC-assessment per IMWG [Kumar, 2016]. 
For analysis purposes, participants with a confirmed CR or better response who do not achieve 
MRD negative status (including missing/inconclusive assessment[s]) and participants without a 
confirmed CR or better response will be considered as having non-negative MRD. MRD 
negativity rate will be summarized by treatment arm. Corresponding two-sided 95% exact CIs 
will also be provided. MRD negativity rate will also be compared between treatment arms using 
the Cochran Mantel Haenszel test stratified by the three randomization factors: number of prior 
lines of therapy, prior bortezomib use, and R-ISS stage. A one-sided p-value will be produced. 
A sensitivity analysis will be performed, with MRD negativity rate defined similarly, but instead 
using investigator confirmed response according to IMWG. 
Supplementary analyses may be performed based on participants with VGPR or better, using 
investigator-assessed and IRC-assessed confirmed response, separately.  
 
Secondary/Explo
ratory 
The following secondary analyses will be conducted: 
CRR, defined as the percentage of participants with a confirmed CR or better (i.e., CR, and 
sCR) as determined by an IRC, according to IMWG criteria [Kumar, 2016]. 
The number and percentage of participants with CR or better as the Best Overall Response 
(BOR) will be summarized by treatment arm. The corresponding exact 95% CI for CRR will also 
be provided. Participants with unknown or missing responses will be treated as 
non-responders, i.e., these participants will be included in the denominator when calculating 
percentages of complete response. CRR will also be compared between treatment arms using 
the Cochran Mantel Haenszel test stratified by randomization factors. The exact 95% CI for the 
difference will be calculated. 
Sensitivity analysis will be conducted using investigator-assessed responses. 
ORR, defined as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, 
CR, and sCR) as determined by an IRC, according to IMWG criteria [Kumar, 2016]. 
The number and percentage of participants with the best confirmed response in the following 
response categories at will be summarized by treatment arm: sCR, CR, VGPR, PR, overall 
response (sCR+CR+VGPR+PR), minimal response (MR), stable disease (SD), progressive 
disease (PD), and not evaluable (NE). The corresponding exact 95% CI for ORR will also be 

 
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Endpoint 
Statistical Analysis Methods 
provided. Participants with unknown or missing responses will be treated as non-responders, 
i.e., these participants will be included in the denominator when calculating percentages of 
response. ORR will also be compared between treatment arms using the Cochran Mantel 
Haenszel test stratified by randomization factors. The exact 95% CI for the difference will be 
calculated. 
CBR, defined as the percentage of participants with a confirmed minimal response (MR) or 
better as determined by an IRC, according to IMWG criteria [Kumar, 2016]. 
The number and percentage of participants with MR or better as the Best Overall Response 
(BOR) will be summarized by treatment arm. The corresponding exact 95% CI for CBR will also 
be provided. Participants with unknown or missing responses will be treated as 
non-responders, i.e., these participants will be included in the denominator when calculating 
percentages of complete response. CBR will also be compared between treatment arms using 
the Cochran Mantel Haenszel test stratified by randomization factors. The exact 95% CI for the 
difference will be calculated. Sensitivity analysis will be conducted using investigator-assessed 
responses. 
VGPR rate, defined as the percentage of participants with a confirmed Very Good Partial 
Response (VGPR) or better (i.e., VGPR, CR, sCR), as determined by an IRC, according to 
IMWG criteria [Kumar, 2016]. 
The number and percentage of participants with VGPR or better as the Best Overall Response 
(BOR) will be summarized by treatment arm. The corresponding exact 95% CI for VGPR rate 
will also be provided. Participants with unknown or missing responses will be treated as 
non-responders, i.e., these participants will be included in the denominator when calculating 
percentages of complete response. VGPR rate will also be compared between treatment arms 
using the Cochran Mantel Haenszel test stratified by randomization factors. The exact 95% CI 
for the difference will be calculated. 
Sensitivity analysis will be conducted using investigator-assessed responses. 
TTR is defined as the time between the date of randomization and the first documented 
evidence of response (PR or better), among participants who achieve a response 
(i.e., confirmed PR or better) as determined by an IRC, according to IMWG criteria [Kumar, 
2016]. 
TTR will be summarized descriptively by treatment arm using medians and quartiles in the 
subset of participants with a confirmed response of PR or better as the BOR. 
Sensitivity analysis will be conducted using investigator-assessed responses. 
TTP is defined as the time from randomization until the earliest date of PD as determined by an 
IRC, according to IMWG criteria [Kumar, 2016], or death due to PD. Determination of dates of 
TTP event and dates for censoring will be described in the SAP. 
TTP analysis will be conducted using similar approach as for the PFS analysis. 
PFS2, defined as time from randomization to disease progression after initiation of new 
anti-myeloma therapy or death from any cause, whichever is earlier. If disease progression 
after new anti-myeloma therapy cannot be measured, a PFS event is defined as the date of 
discontinuation of new anti-myeloma therapy, or death from any cause, whichever is earlier. 
Distribution of PFS2 for each treatment arm will be estimated using the Kaplan-Meier method. 
PFS2 will be compared using similar approach for PFS. Analysis for PFS2 will use investigator-
assessed responses. 
TTBR, defined as the interval of time between the date of randomization and the earliest date of 
achieving best response among participants who achieve a response (i.e., confirmed PR or 
better) as determined by an IRC, according to IMWG criteria [Kumar, 2016]. 

 
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Endpoint 
Statistical Analysis Methods 
Sustained MRD negativity rate, defined as Sustained MRD Negativity rate: defined as the 
percentage of participants with MRD negativity confirmed by NGS minimum of one year apart, 
per IMWG criteria. 
Imaging plus MRD negativity, defined as the percentage of participants who are MRD 
negative by NGS and who have no evidence of disease on PET-CT. 
 
9.5.2. 
Safety Analyses 
All safety analyses will be performed on the Safety Population. 
Table 26 
Statistical Analytical Methods: Safety 
Endpoint 
Statistical Analysis Methods 
Secondary 
Adverse Events: All adverse events, whether serious or non-serious, will be reported from the 
start of treatment until at least 70 days after the last dose of study treatment, until the 
participant withdraws consent for study participation, or until the participant starts subsequent 
anti-myeloma therapy, whichever occurs first. AEs will be recorded using standard medical 
terminology and graded according to the NCI-CTCAE, Version 5.0. For AE reporting, the 
verbatim term used in the eCRF by investigators to identify adverse events will be coded using 
the latest version of MedDRA coding dictionary [NCI, 2010]. 
Adverse events will be summarized by frequency and proportion of total participants, by system 
organ class and preferred term. Separate summaries will be given for all AEs, common (>5%) 
AEs, treatment-related AEs, SAEs, and AEs leading to dose delays and discontinuation of 
study treatment and AEs of special interest. Adverse events, if listed in the NCI-CTCAE 
(Version 5.0) or detailed in Section 10.9 will be summarized by the maximum grade. 
Characteristics (e.g., number of occurrences, action taken, grade, etc.) of the following safety 
profile of clinical interest will be summarized separately:  
• 
The incidence of deaths and the primary cause of death will be summarized. 
• 
Clinical laboratory evaluation: The evaluation of clinical laboratory tests will focus on 
selected laboratory analytes from the hematology and blood chemistry panel. 
• 
Descriptive statistics (mean, standard deviation, median, range) will be used to 
summarize change from baseline in observed value at each scheduled visit. 
The worst-case toxicity grade in hematology and chemistry result during the treatment will be 
summarized. 
Exploratory 
Other Safety Measures: Data for vital signs and ophthalmic examination findings will be 
summarized. For continuous variables, these summaries will include sample size, mean, 
median, standard deviation, minimum, and maximum. For categorical variables, the summaries 
will include frequencies and corresponding percentages. Details will be provided in the SAP. 
 
9.5.3. 
Pharmacokinetic Analyses 
Concentration-Time Data: Linear and semi-logarithmic individual concentration-time 
profiles and median profiles (when appropriate) may be plotted for belantamab mafodotin 
(ADC and total mAb, if available) and cys-mcMMAF. Concentrations of belantamab 

 
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mafodotin (ADC and total mAb, if available) and cys-mcMMAF will be listed for each 
participant and summarized (when appropriate) by planned time point. 
Derived Pharmacokinetic Parameters: Plasma belantamab mafodotin, and/or 
cys-mcMMAF concentration-time data may be combined with data from other studies 
and analyzed using a population pharmacokinetic approach. The initial analysis will use 
the current population pharmacokinetic model at the time of the analysis  to generate post 
hoc pharmacokinetic parameter estimates for the individual participants in Arm A of 
Study 207503. Results may be reported separately. Concentration-time data from the 
participants with enhanced PK schedule may also be analyzed using standard non-
compartmental approach. 
9.5.4. 
Pharmacokinetic/PD Analyses 
If deemed appropriate and if data permit, exposure-response relationships between 
belantamab mafodotin exposure (e.g., dose, dose intensity, concentration, Cmax, or 
AUC) and clinical activity and/or toxicity (e.g., response, corneal event) may be explored 
using population methods. If data permit, the effects of covariates may be explored. 
Results may be reported separately. 
9.5.5. 
Other Analyses 
PK, pharmacodynamic, and biomarker exploratory analyses will be described in the 
statistical analysis plan or in a separate statistical analysis plan (e.g. biomarker clinical 
study plan). The population PK analysis and pharmacodynamic analyses may be 
presented separately from the main clinical study report (CSR). 
9.6. 
Planned Analyses 
9.6.1. 
Periodic IDMC Safety Reviews and CPMS Early Access 
Safety data will be reviewed periodically starting from when 
 
, and then every 
 or as requested by the IDMC thereafter. 
IDMC will review efficacy and safety data at the interim analysis. 
GSK CPMS analysts or delegate(s) not involved in the study conduct will have access to 
a blinded population PK dataset (including, but not limited to, concentration, actual 
dosing information, demographics, and some vital sign and laboratory information, but 
excluding adverse event and efficacy information) at several time points (e.g., prior to 
interim and primary PFS analyses) throughout the trial for population PK model 
development/refinement. Additionally, designated representatives not involved with 
study conduct may be unblinded for performing population PK and PKPD dataset 
preparation in support of planned analyses and PK display review. All other personnel 
will remain blinded to aggregate data by treatment group until database lock. 
9.6.2. 
Interim Analyses 
Three interim analyses (IAs) are planned for the study, including an interim analysis at 
the time of Primary PFS analysis (Table 27). Additional descriptive analyses of OS may 
be performed without alpha-adjustment, only if requested by health authorities. 
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Table 27 
 
Summary of Planned Interim Analyses 
Analysis 
Purpose 
Timing 
Interim Analysis 1 
(IA1) 
Efficacy 
Primary PFS 
Analysis / Interim 
Analysis 2 (IA2) 
Efficacy. This 
will also be the 
planned primary
analysis of PFS.
Interim Analysis 3 
(IA3) 
Efficacy 
 
An interim analysis (IA1) is planned at the time of approximately
 targeted 
PFS events 
% information fraction) have been observed. The interim analysis will 
allow for stopping early for efficacy. All participants are expected to have been enrolled 
at the time of the interim analysis. The Lan-DeMets (O’Brien-Fleming) alpha spending 
function will be used to define the efficacy boundary based on the actual observed 
number of PFS events. 
Boundary crossing probabilities for each of the planned PFS analyses for efficacy based 
on the targeted
PFS events are provided in Table 28 The boundaries will be revised 
based on the observed number of PFS events at the time of analysis. 
If PFS demonstrates statistical significance at IA1 (see Section 9.2), the rationale for 
Primary PFS analysis will be driven by the requirements for OS (PFS will not be 
retested). The timing of subsequent analyses will be determined based on the OS 
information fraction. Details of the boundaries and boundary crossing probabilities for 
each of the planned OS analyses will be provided in the SAP. OS boundaries will be 
based on the observed number of OS events at the time of analysis. 
 
Table 28 
 
Stopping Boundaries for PFS Interim and Primary Analyses 
 
Information 
fraction 
 
N of 
events 
 
Cum. α 
Spent 
 
Efficacy 
Boundary 
(p-value) 
 
Efficacy 
Boundary 
(HR) 
Incremental Boundary 
Crossing Probabilities 
Under H0 
Under H1 
 
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Details of further and any future analyses for key secondary endpoints will be outlined 
within the SAP.   
9.6.3. 
Final Analysis 
The final OS analysis will occur 5 years from Last Participant First Visit (LSFV), or 
when all participants have died, withdrawn consent, or have been lost to follow-up, 
whichever occurs first. For participants still on active treatment at the time of final OS 
analysis (End of Study) please refer to Section 6.7. 
9.6.4. 
Sequence of Interim and Other Planned Analyses 
All planned analyses are listing in Table 29 below. 
Table 29 
 
Details of Planned Analyses 
Analysis 
Reason/impact Timing 
Endpoints included  Data to be 
used 
Safety review 
by IDMC 
Safety review 
Reviewed 
periodically 
starting from 
when
 
 
 
 and 
then every  
 or as 
requested by the 
IDMC thereafter. 
Key safety (AEs, 
SAEs, AESIs, 
deaths, ocular, 
exposure, dose 
modifications, 
laboratory 
parameters), 
descriptive efficacy 
summaries (e.g. 
response rates, 
counts of PFS/OS 
events, if requested) 
and study population 
summaries. 
All data 
available at the 
time of the data 
cut 
Interim 
Analysis 1 
(IA1) 
Efficacy 
 
 
 
 
 
 
Minimally, key safety, 
study population and 
PFS. Additional 
analyses may be 
performed to support 
decision making if 
requested by IDMC.  
 
 
 
. 
All data 
available at the 
time of the data 
cut 
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Analysis 
Reason/impact Timing 
Endpoints included  Data to be 
used 
Primary PFS 
analysis / 
Interim 
Analysis 2 
(IA2) 
Efficacy. This 
will also be the 
planned primary 
analysis of 
PFS. 
All endpoints.  
 
 
 
 
All data 
available at the 
time of the data 
cut 
Interim 
Analysis 3 
(IA3) 
Efficacy 
All data 
available at the 
time of the data 
cut 
Final analysis 
To ensure OS 
data is more 
mature and 
provide updated 
efficacy and 
safety 
All data  
 
 
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with: 
– 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 Brochure, and other 
relevant documents (e.g., 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 and regulatory authority 
approval before implementation of changes made to the study design, as per 
national requirements, except for changes necessary to eliminate an immediate 
hazard to study participants.  
• 
The investigator will be responsible for the following: 
– Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/IEC 
– Notifying the IRB/IEC of SAE 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 Clinical 
Trials Directive 2001/20/EC, and all other applicable local regulations 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 

 
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10.1.3. 
Informed Consent Process 
• 
The investigator or his/her representative will explain the nature of the study to 
the participant or his/her legally authorized representative and answer all 
questions regarding the study. 
• 
Participants must be informed that their participation is voluntary. Participants 
or their legally authorized representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center. 
• 
The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study. 
• 
A copy of the ICF(s) must be provided to the participant or the participant’s 
legally authorized representative. 
10.1.4. 
Data Protection 
• 
Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred. 
• 
GSK will ensure protection of the personal data of the investigator and site staff 
which is collected within the framework of and for the purpose of the study. 
• 
The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant.  
• 
The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorized personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities. 
• 
The contract between sponsor and study sites specifies responsibilities of the 
parties related data protection, including handling of data security breaches and 
respective communication and cooperation of the parties. 
• 
Information technology systems used to collect, process, and store study-related 
data are secured by technical and organizational security measures designed to 
protect such data against accidental or unlawful loss, alteration, or unauthorized 
disclosure or access. GSK and/or trusted third parties working on behalf of GSK 
and/or institutions working with GSK for the purposes of this study are 
contractually bound to protect participant coded data. GSK will protect 
participant coded data and will only share it as described in the ICF. 

 
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10.1.5. 
Committees Structure 
Safety Review Team (SRT) 
A safety review team (SRT) is in place for each GSK product. It comprises of a global 
cross-functional team responsible for the ongoing assessment of benefit-risk for a 
product. The SRT contribute to the continual assessment of incoming new efficacy and 
safety information. 
Independent Data Monitoring Committee (IDMC) 
• An Independent Data Monitoring Committee (IDMC) consisting of at least 
2 physicians and 1 statistician as defined in the IDMC Charter will review data 
from the interim analysis and periodic safety reviews. Details of the interim 
analyses are included in Section 9.6.2. Details of safety reviews are included in 
Section 9.6.1. 
• Ad hoc meetings may be convened at the discretion of the IDMC or if requested 
by the sponsor. Additional details will be provided in the IDMC Charter. 
Independent Review Committee (IRC) 
An IRC, (BioClinica. Inc a Clario company) will be utilized to assess response and 
disease progression per IMWG criteria. The IRC will remain blinded to all treatment arm 
assignments, as no treatment information will be provided to the IRC members. Data 
required for IRC assessment (e.g. laboratory, imaging and bone marrow data) will be 
reviewed and adjudicated. Further details on the IRC process will be defined in the IRC 
charter. Results from the IRC will not be provided to the investigator sites. 
10.1.6. 
Publication Policy 
• 
The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments. 
• 
The sponsor will comply with the requirements for publication of study results. 
In accordance with standard editorial and ethical practice, the sponsor will 
generally support publication of multicenter studies only in their entirety and not 
as individual site data. In this case, a coordinating investigator will be 
designated by mutual agreement. 
• 
Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements. 
10.1.7. 
Dissemination of Clinical Study Data 
• 
Disclosure of Clinical Study Reports (CSRs), periodic safety reports, and 
clinical study summary reports after review by regulatory authorities. This 
includes access to CSRs from studies with negative outcomes and from 
terminated development programs. 

 
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• 
The posting of company-sponsored study information and tabular study results 
on the US National Institutes of Health’s website www.ClinTrials.gov and other 
publicly-accessible sites.  
• 
Publication planning and other activities related to non-promotional, peer-
reviewed publications, to ensure the scientific integrity and credibility of 
publication activities performed by or on behalf of the company. The granting of 
access to analyzable datasets from clinical studies through a secure system, 
following an independent assessment of the scientific merit of a rigorously 
defined research question from a third party.  
• 
Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report. The investigator 
will be provided reasonable access to statistical tables, figures, and relevant 
reports and will have the opportunity to review the complete study results at a 
GSK site or other mutually-agreeable location. 
• 
GSK will also provide the investigator with the full summary of the study 
results. The investigator is encouraged to share the summary results with the 
study participants, as appropriate. 
• 
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK 
Policy. 
• 
A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 
10.1.8. 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g., 
laboratory data). The investigator is responsible for verifying that data entries 
are accurate and correct by physically or electronically signing the eCRF.  
• 
The investigator must maintain accurate documentation (source data) that 
supports the information entered in the eCRF.  
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.  
• 
Study monitors will perform ongoing source data verification to confirm that 
data entered into the eCRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants 
are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  

 
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• 
Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without 
written notification to the sponsor.  
Additional information regarding remote data management and monitoring are provided 
in Section 10.16, Appendix 16. 
10.1.9. 
Source Documents 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• 
Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. 
The investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be 
available. 
• 
Definition of what constitutes source data can be found in SRM. 
10.1.10. 
Study and Site Closure 
Start of study and first act of recruitment 
The start of study and the first act of recruitment are defined as FSFV (first ICF signature 
date) at a country-level. 
Study/Site termination 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
For study termination: 
• 
Discontinuation of further study intervention development. 

 
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For site termination: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate or no recruitment (evaluated after a reasonable amount of time) of 
participants by the investigator 
• 
Total number of participants included earlier than expected. 
If the study is prematurely terminated or temporarily suspended, the sponsor shall 
promptly inform the investigators, the IECs/IRBs, the regulatory authorities, and any 
contract research organization(s) used in the study of the reason for termination or 
temporary suspension, as specified by the applicable regulatory requirements. The 
investigator shall promptly inform the participant and should assure appropriate 
participant therapy and/or follow-up. 

 
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10.2. 
Appendix 2: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.2.1. 
Definition of AE 
AE Definition 
• An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study treatment, whether or not considered 
related to the study treatment. 
• NOTE: 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 study treatment. 
 
Events Meeting the AE Definition  
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study treatment administration even 
though they may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses must be reported regardless of sequelae. 
• 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not 
be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting 
from lack of efficacy will be reported as AE or SAE if they fulfil the definition of 
an AE or SAE.  
 
Events NOT Meeting the AE Definition  
• Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• The disease/disorder being studied or expected progression, signs, or symptoms of 

 
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Events NOT Meeting the AE Definition  
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
10.2.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
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 were more severe. 
c. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AE. If a 
complication prolongs hospitalization or fulfils any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE must be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 

 
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A SAE is defined as any untoward medical occurrence that, at any dose: 
d. Results in persistent disability/incapacity 
• The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Other situations: 
• Medical or scientific judgment must be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events must 
usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
g. Is associated with liver injury and impaired liver function defined as: 
• ALT 3 x ULN and total bilirubin* 2 x ULN (>35% direct), or 
• ALT 3 x ULN and INR** >1.5 
* Serum bilirubin fractionation should be performed if testing is available; if 
unavailable, measure urinary bilirubin via dipstick. If fractionation is unavailable and 
ALT 3 x ULN and total bilirubin 2 x ULN, then the event is still to be reported as an 
SAE. 
** INR testing not required per protocol and the threshold value does not apply to 
participants receiving anticoagulants. If INR measurement is obtained, the value is to 
be recorded on the SAE form. 
h. Refer to Section 10.4.1 for liver chemistry follow-up procedures. 
 

 
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10.2.3. 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the eCRF for the 
following AEs and SAEs: 
• Myocardial infarction/unstable angina 
• Congestive heart failure 
• Arrhythmias 
• Valvulopathy 
• Pulmonary hypertension 
• Cerebrovascular events/stroke and transient ischemic attack 
• Peripheral arterial thromboembolism 
• Deep venous thrombosis/pulmonary embolism 
• Revascularization 
10.2.4. 
Recording and Follow-Up of AE and SAE 
AE and SAE Recording 
• When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• The investigator will then record all relevant AE/SAE information in the eCRF. 
• It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK /AE/SAE eCRF page. 
• There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will assess intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories:  
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 

 
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• Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting 
age appropriate instrumental ADL*. 
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-
care ADL**. 
• Grade 4: Life-threatening consequences; urgent intervention indicated. 
• Grade 5: Death related to AE. 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using 
the telephone, managing money, etc. 
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the 
toilet, taking medications, and not bedridden. 
 
Assessment of Causality 
• The investigator is obligated to assess the relationship between study treatment and 
each occurrence of each AE/SAE. 
• A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• The investigator will use clinical judgment to determine the relationship. 
• Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study treatment 
administration will be considered and investigated. 
• The investigator will also consult the IB and/or Product Information, for marketed 
products, in his/her assessment. 
• For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality. 
• There may be situations in which an SAE has occurred, and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK. 
• The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
 

 
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Follow-up of AE and SAE 
• The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
• New or updated information will be recorded in the originally completed eCRF. 
• The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
10.2.5. 
Reporting of SAEs to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• 
The primary mechanism for reporting SAEs to GSK will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection tool 
has been taken off-line, then the site can report this information on a paper SAE 
form (see next section). 
• 
Contacts for SAE reporting can be found in the SRM. 
 
SAE Reporting to GSK via Paper CRF 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to the SAE coordinator. Details provided in the SRM. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time 
frames. 
• 
Contacts for SAE reporting can be found in the SRM. 

 
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10.3. 
Appendix 3: Contraceptive Guidance and Collection of 
Pregnancy Information 
10.3.1. 
Definitions 
Woman of childbearing potential (WOCBP): 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 
Women in the following categories are not considered WOCBP: 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other 
than the above (e.g., mullerian agenesis, androgen insensitivity), investigator 
discretion should be applied to determining study entry. 
Note:  Documentation can come from the site personnel’s review of participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
• 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high follicle stimulating hormone (FSH) level in 
the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or hormonal replacement therapy 
(HRT). However, in the absence of 12 months of amenorrhea confirmation with 
more than 1 FSH measurement is required [in questionable cases a blood sample 
with simultaneous FSH >40 MIU/mL and estradiol <40 pg/mL (<147 pmol/L) is 
confirmatory].  
• 
Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-oestrogen hormonal highly effective contraception methods if 
they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment. 

 
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10.3.2. 
Contraception Guidance 
CONTRACEPTIVESa ALLOWED DURING THE STUDY 
Highly Effective Methodsb That Have Low User Dependency: 
• 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)c 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner 
– Note: Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. Spermatogenesis cycle is approximately 90 days. 
Highly Effective Methodsb That Are User Dependent: 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
– oral 
– intravaginal 
– transdermal 
– injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
– oral 
– injectable 
• 
Sexual abstinence 
– Note: Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with 
the study intervention. The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the study and the preferred and usual lifestyle of the 
participant. 
a. 
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b. 
Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 

 
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c. 
Male condoms must be used in addition to hormonal contraception. If locally required, in accordance with 
Clinical Trial Facilitation Group guidelines, acceptable contraceptive methods are limited to those which inhibit 
ovulation as the primary mode of action. 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method are not acceptable methods of contraception for this study. 
Male condom and female condom should not be used together (due to risk of failure with friction). 
 
10.3.3. 
Collection of Pregnancy Information 
Male participants with partners who become pregnant: 
• Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while participating in this study and for 6 
months following the last dose of belantamab mafodotin (Arm A) and 4 months 
following the last dose of bortezomib, whichever is longest, by telephone for 
WOCBP partners only. This applies only to male participants who receive study 
treatment. 
• After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the appropriate 
form and submit it to GSK within 24 hours of learning of the partner’s pregnancy.  
• The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to GSK. 
• Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of fetal 
status (presence or absence of anomalies) or indication for procedure. 
Female participants who become pregnant: 
• Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study and for 4 months following the last 
dose of belantamab mafodotin (Arm A), 3 months from the last dose of daratumumab 
(Arm B) or 7 months from the last dose of bortezomib, whichever is longest.  
• Information will be recorded on the appropriate form and submitted to GSK within 24 
hours of learning of a participant's pregnancy.  
• Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on participant and neonate, which will 
be forwarded to GSK. Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date.  
• Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure.  
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE.  
• A spontaneous abortion is always considered to be an SAE and will be reported as 
such.  

 
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• Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to GSK 
as described in Section 10.2. While the investigator is not obligated to actively seek 
this information in former study participants, he or she may learn of an SAE through 
spontaneous reporting.  
• Any female participant who becomes pregnant while participating will discontinue 
study treatment. 

 
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10.4. 
Appendix 4: Liver Safety: Required Actions, Follow-up 
Assessments, and Study Treatment Rechallenge Guidelines 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology. 
Liver Chemistry Stopping Criteria –Liver Stopping Event 
ALT-absolute 
ALT 8xULN 
ALT Increase 
ALT 5xULN but <8xULN persists for 2 weeks 
ALT 3xULN but <5xULN persists for 4 weeks 
Bilirubin1, 2 
ALT 3xULN and total bilirubin  2xULN 
INR2  
ALT 3xULN and INR>1.5 
Cannot Monitor 
ALT 5xULN but <8xULN and cannot be monitored weekly for 2 weeks 
ALT 3xULN but <5xULN and cannot be monitored weekly for 4 weeks 
Symptomatic3 
ALT 3xULN associated with symptoms (new or worsening) believed to be related to 
liver injury or hypersensitivity 
Required Actions, Monitoring and Follow up Assessments 
Actions 
Follow Up Assessments 
• 
Immediately discontinue study intervention 
• 
Report the event to GSK within 24 hours 
• 
Complete the liver event form and complete SAE data 
collection tool if the event also meets the criteria for 
an SAE2 
• 
Perform liver event follow up assessments as 
described in the Follow up Assessment column 
• 
Monitor the participant until liver chemistries resolve, 
stabilize, or return to within baseline (see 
MONITORING) 
MONITORING: 
If ALT 3xULN AND total bilirubin 2xULN or INR >1.5: 
• 
Repeat liver chemistries (include ALT, AST, alkaline 
phosphatase, total bilirubin and INR) and perform liver 
event follow up assessments within 24 hours 
• 
Monitor participants twice weekly until liver 
chemistries resolve, stabilize or return to within 
baseline 
• 
A specialist or hepatology consultation is 
recommended 
For All other criteria (bilirubin <2xULN and INR 1.5):  
• 
Repeat liver chemistries (include ALT, AST, alkaline 
phosphatase, total bilirubin and INR) and perform 
liver event follow up assessments within 24-72 hours 
• 
Viral hepatitis serology4 
• 
Obtain INR and recheck with each liver 
chemistry assessment until the 
aminotransferases values show downward trend 
• 
Blood sample for pharmacokinetic (PK) analysis 
and a blood sample for sBCMA, obtained within 
70 days after last dose of belantamab 
mafodotin5 
• 
Serum creatine phosphokinase (CPK) and 
lactate dehydrogenase (LDH), gamma glutamyl 
transferase [GGT], glutamate dehydrogenase 
[GLDH], and serum albumin 
• 
Fractionate bilirubin, if total bilirubin 2xULN 
• 
Obtain complete blood count with differential to 
assess eosinophilia 
• 
Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity, on 
the liver event form 
• 
Record use of concomitant medications on the 
concomitant medications report form including 
acetaminophen, herbal remedies, recreational 
drugs and other over the counter medications 
• 
Record alcohol use on the liver event alcohol 
intake form 
If ALT 3xULN AND total bilirubin 2xULN or INR 
>1.5 obtain the following in addition to the 
assessments listed above: 

 
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• 
Monitor participants weekly until liver chemistries 
resolve, stabilize or return to within baseline 
RESTART/RECHALLENGE 
• 
Restart/rechallenge is allowed per protocol but do 
not resume study intervention unless GSK 
approval is granted; If restart/rechallenge is not 
granted, permanently discontinue study intervention 
and continue participant in the study for any protocol 
specified follow up assessments. Refer to 
Restart/Rechallenge guidelines in Section 10.4.1. 
• Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney microsomal 
antibodies, and quantitative total immunoglobulin G 
(IgG or gamma globulins) 
• Serum acetaminophen adduct assay should be 
conducted (where available) to assess potential 
acetaminophen contribution to liver injury unless 
acetaminophen use is very unlikely in the 
preceding week. (e.g., where the participant has 
been resident in the clinical unit throughout)  
• Liver imaging (ultrasound, magnetic resonance, or 
computerised tomography) to evaluate liver 
disease; complete Liver Imaging form 
• Liver biopsy may be considered and discussed 
with local specialist if available, for instance: 
o 
In patients when serology raises the 
possibility of autoimmune hepatitis (AIH) 
o 
In patients when suspected DILI 
progresses or fails to resolve on withdrawal 
of study intervention 
o 
In patients with acute or chronic atypical 
presentation:  
• If liver biopsy conducted complete liver biopsy 
form. 
1. 
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention for that participant if ALT 3xULN and total bilirubin 
2xULN. Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable 
urinary bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury. 
2. 
All events of ALT 3xULN and total bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN and INR >1.5, 
which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding studies 
of hepatic impairment or cirrhosis); the INR threshold value stated will not apply to participants receiving 
anticoagulants. 
3. 
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, 
rash or eosinophilia). 
4. 
Includes: Hepatitis A IgM antibody; Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM); Hepatitis 
C RNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing); Hepatitis E IgM antibody [Le Gal, 2005]. 
5. 
PK sample may not be required for participants in Treatment Arm B receiving daratumumab/bor/dex. Record 
the date/time of the PK/sBCMA blood sample draw and the date/time of the last dose of study intervention prior 
to blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK/sBCMA sample cannot be 
collected in the time period indicated above, do not obtain a PK/sBCMA sample. Instructions for sample 
handling and shipping are in the SRM. A sample for sBCMA should be collected at the time of PK sample 
collection. 

 
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Phase III-IV liver chemistry increased monitoring criteria with continued therapy  
Liver Chemistry Increased Monitoring Criteria and Actions with Continued Study Intervention Liver 
Monitoring Event 
Criteria 
Actions 
ALT 5xULN and <8xULN and total bilirubin <2xULN 
or INR ≤1.5 without symptoms believed to be related 
to liver injury or hypersensitivity, and who can be 
monitored weekly for 2 weeks. 
OR 
ALT 3xULN and <5xULN and total bilirubin <2xULN 
or INR ≤1.5 without symptoms believed to be related 
to liver injury or hypersensitivity, and who can be 
monitored weekly for 4 weeks. 
• 
Notify the GSK medical monitor within 24 hours of 
learning of the abnormality to discuss participant 
safety.  
• 
Participant can continue study intervention 
• 
Participant must return weekly for repeat liver 
chemistries (ALT, AST, alkaline phosphatase, total 
bilirubin and INR) until they resolve, stabilise or return 
to within baseline  
• 
If at any time participant meets the liver chemistry 
stopping criteria, proceed as described above 
• 
If ALT decreases from ALT 5xULN and <8xULN to 
≥3xULN but <5xULN (total bilirubin <2xULN and INR 
≤1.5), continue to monitor liver chemistries weekly.  
• 
If, after 4 weeks of monitoring, ALT <3xULN and 
bilirubin <2xULN and INR ≤1.5, monitor participants 
twice monthly until liver chemistries resolve or return 
to within baseline. 
References 
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee WM. Pharmacokinetics of 
Acetaminophen-Adduct in Adults with Acetaminophen Overdose and Acute Liver Failure. Drug Metab Dispos 
2009; 37:1779-1784. 
Le Gal F, Gordien E, Affolabi D, Hanslik T, Alloui C, Dény P, Gault E. Quantification of Hepatitis Delta Virus RNA in 
Serum by Consensus Real-Time PCR Indicates Different Patterns of Virological Response to Interferon Therapy 
in Chronically Infected Patients. J Clin Microbiol. 2005;43(5):2363–2369.  
10.4.1. 
Liver Safety Drug Restart or Re-Challenge Guidelines 
A participant who met liver chemistry stopping criteria cannot resume study intervention 
unless all of the following conditions are met: 
• 
GSK approval is granted (as described below), 
• 
Institutional Review Board/Independent Ethics Committee (IRB/IEC) approval 
is obtained, if required, and 
• 
Separate ICF for study intervention restart/rechallenge is signed by the 
participant and participant is informed of any associated risks 
If GSK approval to restart/rechallenge participant with study intervention is not granted, 
then participant must permanently discontinue study intervention and may continue in the 
study for protocol-specified follow up assessments. 
10.4.1.1. 
Rechallenge Following Liver Stopping Events that are Possibly Related 
to Study Treatment 
Following drug-induced liver injury (DILI), drug rechallenge is associated with a 13% 
mortality rate across all drugs in prospective studies [Andrade, 2009]. Clinical 
outcomes vary by drug, with nearly 50% fatality with halothane re-administered within 

 
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one month of initial injury. However, some drugs seldom result in recurrent liver injury 
or fatality.  
Risk factors for a fatal drug rechallenge outcome include: 
• 
Hypersensitivity with initial liver injury (e.g., fever, rash, eosinophilia) 
[Andrade, 2009]  
• 
Jaundice or bilirubin >2 x ULN with initial liver injury (direct bilirubin >35% of 
total) 
• 
Ongoing severe liver injury defined by: ALT ≥3 × ULN, bilirubin ≥2 × ULN 
(direct bilirubin >35% of total), or INR ≥1.5. 
• 
SAEs or fatality has earlier been observed with drug rechallenges [Hunt, 2010; 
Papay, 2009]. 
• 
Evidence of drug-related preclinical liability (e.g., reactive metabolites; 
mitochondrial impairment) [Hunt, 2010] 
Rechallenge refers to resuming study treatment following study treatment induced liver 
injury, DILI. Because of the risks associated with rechallenge after DILI, this should only 
be considered for a participant for whom there is compelling evidence of benefit from a 
critical or life-saving medicine, there is no alternative approved medicine available, and a 
benefit:risk assessment of rechallenge is considered to be favorable. 
Approval by GSK for rechallenge with study treatment can be considered where: 
• 
The PI requests consideration of rechallenge with study treatment for a participant 
who is receiving compelling benefit with study treatment that exceeds risk, and no 
effective alternative therapy is available.  
• 
IRB/IEC approval for rechallenge with study treatment must be obtained. 
If the rechallenge is approved by GSK in writing: 
• 
The participant must be provided with a clear description of the possible benefits and 
risks of study treatment administration, including the possibility of recurrent, more 
severe liver injury or death.  
• 
The participant must also provide signed informed consent specifically for the 
rechallenge with study treatment. Documentation of informed consent must be 
recorded in the study file.  
• 
Study treatment must be administered at the dose specified by GSK. 
• 
Participants approved by GSK Medical Governance for rechallenge with study 
treatment must return to the clinic twice a week for liver chemistry tests until stable 
liver chemistries have been demonstrated and then standard laboratory monitoring 
may resume as per protocol. 
• 
If after study treatment rechallenge, participant meets protocol-defined liver 
chemistry stopping criteria, study treatment should be permanently discontinued.  

 
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• 
GSK Medical Monitor, and the IRB/IEC as required, must be informed of the 
participant’s outcome following study treatment rechallenge.  
• 
GSK to be notified of any adverse events, as per Section 10.2. 
10.4.1.2. 
Restart Following Transient Resolving Liver Stopping Events NOT 
Related to Study Treatment 
Restart refers to resuming study treatment following liver stopping events in which there 
is a clear underlying cause (other than DILI) of the liver event (e.g., biliary obstruction, 
pancreatic events, hypotension, acute viral hepatitis). Furthermore, restart is not permitted 
following liver stopping event when the underlying cause was alcohol-related hepatitis. 
Approval by GSK for study treatment restart can be considered where: 
• 
Investigator requests consideration for study treatment restart if liver chemistries 
have a clear underlying cause (e.g., biliary obstruction, hypotension and liver 
chemistries have improved to normal or are within 1.5 x baseline and ALT <3 x 
ULN). 
• 
Possible study treatment-induced liver injury has been excluded by the Principal 
Investigator and the study team. This includes the absence of markers of 
hypersensitivity (otherwise unexplained fever, rash, eosinophilia). Where a study 
treatment has an identified genetic marker associated with liver injury (e.g., 
lapatinib, abacavir, amoxicillin/clavulanate), the presence of the marker should be 
excluded. If study treatment-related liver injury cannot be excluded, the guidance on 
rechallenge as stated in previous section will apply. 
• 
There is no evidence of alcoholic hepatitis. 
• 
IRB/IEC approval of study treatment restart must be obtained, as required. 
• 
If restart of study intervention is approved by GSK in writing: The participant 
must be provided with a clear description of the possible benefits and risks of study 
treatment administration, including the possibility of recurrent, more severe liver 
injury or death. 
• 
The participant must also provide signed informed consent specifically for the study 
treatment restart. Documentation of informed consent must be recorded in the study 
file. 
• 
Study treatment must be administered at the dose specified by GSK. 
• 
Participants approved by GSK for restart of study treatment must return to the clinic 
once a week for liver chemistry tests until stable liver chemistries have been 
demonstrated and then laboratory monitoring may resume as per protocol.  
• 
If participant meets protocol-defined liver chemistry stopping criteria after study 
treatment restart, study treatment should be permanently discontinued. 
• 
GSK Medical Monitor, and IRB/IEC must be informed of the participant’s outcome 
following study treatment restart.  
• 
GSK to be notified of any adverse events, as per Section 10.2. 

 
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10.5. 
Appendix 5: Genetics 
USE/ANALYSIS OF DNA 
• 
Genetic variation may impact a participant’s response to study intervention, 
susceptibility, severity and progression of disease. Variable response to study 
intervention may be due to genetic determinants that impact drug absorption, 
distribution, metabolism, and excretion; mechanism of action of the drug; disease 
etiology; and/or molecular subtype of the disease being treated. Therefore, where 
local regulations and IRB/IEC allow, a blood sample will be collected for DNA 
analysis. 
• DNA samples will be used for research related to belantamab mafodotin or multiple 
myeloma and related diseases. They may also be used to develop tests/assays 
(including diagnostic tests) related to belantamab mafodotin or study interventions of 
this drug class, and multiple myeloma. Genetic research may consist of the analysis 
of 1 or more candidate genes or the analysis of genetic markers throughout the 
genome or analysis of the entire genome (as appropriate). 
• DNA samples will be analyzed for relationships between genetic variants in the host 
and response to belantamab mafodotin. A detailed description of any planned 
analyses will be documented in a Statistical Analysis Plan (SAP) prior to initiation of 
analyses. Planned analyses and results of genetic investigations will be reported either 
as part of the clinical SAP and clinical study report (CSR), or in a separate genetics 
SAP and report, as appropriate.  
• The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to belantamab mafodotin or study interventions of this class. 
The results of genetic analyses may be reported in the clinical study report or in a 
separate study summary. 
• 
The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality.  
• The samples will be retained while research on belantamab mafodotin (or study 
interventions of this class) or multiple myeloma continues but no longer than 15 years 
after the last participant last visit or other period as per local requirements. 
 

 
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10.6. 
Appendix 6: Eastern Cooperative Oncology Group (ECOG) 
Functional Status 
Performance Grade 
Description 
0 
Normal activity. Fully active, able to carry on all pre-disease performance without 
restriction. 
1 
Symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory 
and able to carry out work of a light or sedentary nature (e.g., light housework.) 
2 
In bed <50% of the time. 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 
In bed >50% of the time. Capable of only limited self-care, confined to bed or chair 
more than 50% of waking hours. 
4 
100% bedridden. Completely disabled. Cannot carry on any self-care. Totally confined 
to bed or chair. 
5 
Dead. 
Source: Oken, 1982. 
 

 
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10.7. 
Appendix 7: Modified Diet in Renal Disease (MDRD) Formula 
The MDRD formula for calculating the estimated glomerular filtration rate (eGFR) is as 
follows: 
eGFR = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if African 
American) 
GFR is expressed in mL/min/1.73 m2, SCr is serum creatinine expressed in mg/dL, and 
age is expressed in years.  
The following link will auto-calculate the creatinine clearance:  
http://nephron.org/cgi-bin/MDRD_GFR/cgi 

 
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10.8. 
Appendix 8: New York Heart Association Classification 
The New York Heart Association (NYHA) Functional Classification: Class I, II, III or IV 
Heart Failure [New York Heart Association, 1994] provides a simple way of classifying 
the extent of heart failure. It places participants in 1 of 4 categories based on the level of 
limitation experienced during physical activity: 
Class 
Symptoms 
Class I 
(Mild) 
No limitation of physical activity. Ordinary physical activity does not cause undue 
fatigue, palpitation or dyspnea (shortness of breath). 
Class II 
(Mild) 
Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity 
results in fatigue, palpitation or dyspnea. 
Class III 
(Moderate) 
Marked limitation of physical activity. Comfortable at rest, but less than ordinary 
physical activity results in fatigue, palpitation or dyspnea. 
Class IV 
(Severe) 
Unable to carry out any physical activity without discomfort. Symptoms of cardiac 
insufficiency at rest. If any physical activity is undertaken, discomfort is increased. 
 

 
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10.9. 
Appendix 9: Corneal Event Grading and Prophylactic 
Interventions for Corneal Toxicity (Treatment Arm A) 
Dose modifications of belantamab mafodotin for treatment-related corneal events should 
be based on grading of corneal events according to the guidelines of Keratopathy Visual 
Acuity (KVA) Scale as provided in Table 30: 
Table 30 
Keratopathy Visual Acuity (KVA) Scale for Treatment-related Corneal 
Events: 
Grade per KVA scale 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Corneal 
Toxicities* 
Corneal 
examination 
finding(s) 
Mild superficial 
keratopathya 
Moderate 
superficial 
keratopathyb 
Severe superficial 
keratopathyc 
Corneal 
epithelial 
defectd 
Change in 
BCVAe 
Decline from 
baseline of 1 line 
on Snellen 
Visual Acuity 
Decline from 
baseline of 2 or 3 
lines (and Snellen 
Visual Acuity not 
worse than 
20/200) 
Decline from 
baseline by more 
than 3 lines (and 
Snellen Visual 
Acuity not worse 
than 20/200) 
Snellen Visual 
Acuity worse 
than 20/200 
*Dose modification should be based on the most severe finding. If eyes differ in severity, dose modification guideline 
should be applied based on the more severe eye. 
a Mild superficial keratopathy = mild superficial punctate keratopathy (documented worsening from baseline), with or 
without symptoms. 
b Moderate superficial keratopathy = any/ or a combination of: moderate superficial punctate keratopathy, patchy 
microcyst-like deposits, sub-epithelial haze (peripheral), or a new peripheral stromal opacity. 
c Severe superficial keratopathy = any/ or a combination of: severe superficial punctate keratopathy, diffuse microcyst-
like deposits involving the central cornea, sub-epithelial haze (central), or a new central stromal opacity. 
d Corneal epithelial defect such as corneal ulcers. Corneal ulcer by definition means an epithelial defect with underlying 
stromal infiltration. 
e Changes in visual acuity due to treatment-related corneal findings.  
• 
For participants who have BCVA worse than 20/20 in either eye at baseline, dose modification for that eye 
will be determined by the worsening of vision from baseline only (not by absolute BCVA at the visits).  
• 
If a participant has a baseline BCVA of 20/200 or worse in an eye, then belantamab mafodotin-related 
changes in vision in the other eye will drive the dose modification. If a participant has baseline BCVA of 
20/200 or worse in both the eyes, then the decision to delay or reduce belantamab mafodotin dose will be 
based on PI’s assessment of benefit vs. risk based on corneal exam findings following a discussion with the 
qualified eye care specialist.  
BCVA- best corrected visual acuity 
 
See Table 11 for dose modification guidelines and stopping criteria for belantamab 
mafodotin treatment-related corneal events based on the KVA scale. 
Prophylactic interventions for corneal toxicity associated with belantamab mafodotin is 
provided in Table 31. 

 
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Table 31 
Prophylactic Measures for Corneal Toxicity Associated with 
Belantamab Mafodotin 
Prophylactic 
Measurea 
Dose and Administration 
Timing 
Preservative-free 
artificial tears 
Administer in each eye at least 4 to 8 times 
daily  
Administer daily beginning on Cycle 1 
Day 1 until EOT.  
Allow at least 5-10 minutes between 
administration of artificial tears and steroid 
eye drops (if administered together) 
Cooling eye mask 
May apply cooling eye mask to both eyes 
for approximately 1 hour or as much as 
tolerated by the participant  
During belantamab mafodotin infusion 
administration in the first hour for up to 4 
hours, as tolerated 
a. 
Dose modifications and treatment for corneal toxicities are discussed in Section 6.6. 
While not yet clinically demonstrated, it is theoretically possible that the application of a 
cooling eye mask during belantamab mafodotin administration, and in the first few hours 
after infusion may decrease ocular side effects.  
Corticosteroid eye drops are not required as prophylaxis but can be used therapeutically if 
clinically indicated per discretion of an eye-care specialist. Allow at least 5-10 minutes 
between administration of artificial tears and steroid eye drops (if administered together). 
If steroid eye drops are deemed medically necessary and prescribed, intraocular pressure 
must be monitored if used for >7 days. 
A qualified eye care specialist (Appendix 10) consult is required for all participants who 
develop signs or symptoms of corneal events or require steroid eye drops for more than 7 
days. 

 
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10.10. 
Appendix 10: Eye Care Specialist’s Qualifications and 
Requirements 
For examiners with a degree in ophthalmology or optometry, those involved in eye 
evaluations in the protocol will, at a minimum be able to provide comprehensive eye care 
to patients, which includes routine check-ups, treatment and ongoing management of 
visual disease. Qualified eye care specialists, including optometrist, will also be able to 
communicate with patients on the effect of belantamab mafodotin on eye. 
Specifically, qualified eye care specialists must be able to: 
• Perform comprehensive eye exams  
• Perform visual Acuity with manual refraction tests and analyse results 
• Perform slit lamp tests and analyse results 
• Perform intraocular pressure examination 
• Dilated fundoscopic examination 
• Diagnose and treat ocular issues and diseases such as keratopathy or glaucoma. 
 

 
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10.11. 
Appendix 11: Progression-Free Survival Event and 
Censoring Rules 
Situation 
Date of Event 
(Progression/Death) or Censored 
Event 
(Progression/Death) or Censored 
No adequate baseline 
assessments1 and the participant 
has not died (if the participant has 
died follow the rules for death 
indicted at the bottom of the table) 
Randomization 
Censored 
No post-baseline assessments and 
the participant has not died (if the 
participant has died follow the rules 
for death indicted at the bottom of 
the table) 
Randomization 
Censored 
Progression documented at 
scheduled visits and Progression 
documented without extended loss-
to-follow-up time2 
Date of assessment of progression 
Event 
Progression documented between 
scheduled visits and Progression 
documented without extended loss-
to-follow-up time2 
Date of assessment of progression 
(S1) min (Date of next scheduled 
visit, date of death) 
Event 
(S1) Event 
With post-baseline assessment but 
no progression (or death) 
Date of last ‘adequate’ assessment 
of response3 
Censored 
No adequate post-baseline 
assessment before start of new 
anti-myeloma therapy 
Randomization 
Censored 
With adequate post-baseline 
assessment and new anti-myeloma 
treatment started (prior to 
documented disease progression)4 
Date of last ‘adequate’ assessment 
of response3 (on or prior to starting 
anti-myeloma therapy)  
(S2) Date of starting new anti-
myeloma therapy 
Censored 
(S2) Event 
Death before first scheduled 
assessment (or death at baseline or 
without any adequate assessments) 
Date of death 
Event 
Death between adequate 
assessment visits 
Date of death 
Event 
Death or progression after missing 
2 or more scheduled assessments2 
Date of randomization if no post-
baseline assessments, or date of 
last ‘adequate’ assessment of 
response3 (prior to missed 
assessments): since disease 
Censored 
(S3) Event 

 
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Situation 
Date of Event 
(Progression/Death) or Censored 
Event 
(Progression/Death) or Censored 
assessment is every 3 weeks, a 
window of 49 days (6 weeks + 7- 
day window) will be used to 
determine whether there is 
extended time without adequate 
assessment. If the time difference 
between PD/death and max(last 
adequate disease assessment, 
randomization) is more than 49 
days, PFS will be censored at the 
last adequate disease assessment 
prior to PD/death. 
(S3) Date of death or progression 
(S4) Treatment discontinuation due 
to clinical PD before PD or death 
(S4) Date of treatment 
discontinuation 
(S4) Event 
Abbreviations: CR=Complete Response; FLC=Free Light Chain; MR=Minimal Response; PD=Progressive Disease; 
PR=Partial Response; sCR=Stringent Complete Response; SD=Stable Disease; VGPR=Very Good Partial 
Response. 
 
Notes:  
(S1) (S2) (S3) (S4) Rules to be applied for PFS Sensitivity Analysis. 
Event or censored are based on confirmed responses. 
 
Footnotes: 
1. 
Adequate baseline assessment is defined as at baseline, a patient has at least one of the following 
measurements: Serum M-protein ≥0.5 g/dL (≥5 g/L) or b. Urine M-protein ≥200 mg/24h or c. Serum FLC 
assay: Involved FLC level ≥10 mg/dL (≥100 mg/L) and an abnormal serum free light chain ratio (<0.26 or 
>1.65) 
2. 
Extended loss-to-follow-up time = 6 weeks + 7 day window = 49 day window; Without extended 
loss-to-follow-up time is defined as: <= 49 days; after an extended loss-to-follow-up time is defined as: >49 
days. 
3. 
An adequate assessment is defined as an assessment where the response is sCR, CR, PR, VGPR, MR, or 
SD. 
4. 
If PD and new anti-myeloma therapy occur on the same day, assume the progression was documented first; 
e.g., outcome is progression and the date is the date of the assessment of progression. 

 
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10.12. 
Appendix 12: Country Specific Requirements 
For requirements specific to Japan, please refer to Appendix 18. 
Inclusion / Exclusion Criteria: 
• 
In Republic of Korea, a participant must be over 19 years of age inclusive, at the 
time of signing the informed consent. 
• 
In France a subject will be eligible for inclusion in this study only if either 
affiliated to or a beneficiary of a social security category 
Adverse Events: 
• 
For all studies conducted in China, SAEs will be collected from signing of the 
ICF and NOT from the start of treatment. 
• 
For Japan, GFR = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (0.808 if 
Japanese) 
Genetics: 
For participants from China, any description in connection with collection and using of 
Human Genetic Resources in this protocol shall be subject to the approval of Human 
Genetics Resources Administration of China (HGRAC). 

 
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10.13. 
Appendix 13: Revised International Staging System for 
Multiple Myeloma 
Prognostic Factor 
Criteria 
ISS Stage 
I 
Serum 2-microglobulin <3.5 mg/L, serum albumin 3.5 g/dL 
II 
Not ISS Stage I or III 
III 
Serum 2-microglobulin 5.5 mg/L 
CA by iFISH 
High Risk 
Presence of del(17p) and/or translocation t(4;14) and/or translocation t(14;16) 
Standard Risk 
No high-risk CA 
LDH 
Normal 
Serum LDH < the upper limit of normal 
High 
Serum LDH  the upper limit of normal 
R-ISS Stage (A new model for risk stratification for MM) 
I 
ISS stage I and standard-risk CA by iFISH and normal LDH 
II 
Not R-ISS Stage I or III 
III 
ISS stage III and either high-risk CA by iFISH or high LDH 
Abbreviations: CA, chromosomal abnormalities; iFISH, interphase fluorescent in situ hybridization; ISS, International 
Staging System; LDH, lactate dehydrogenase; MM, multiple myeloma; R-ISS, revised International Staging System 
Source: Palumbo, 2015b 

 
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10.14. 
Appendix 14: Abbreviations, Definitions and Trademarks 
Abbreviations 
ABO 
Blood grouping system 
ADA 
Anti-drug antibodies 
ADC 
Antibody-drug conjugate 
ADCC 
Antibody-dependent cellular cytotoxicity 
ADE 
Adverse device effect 
ADL 
Activities of daily living 
AE 
Adverse event 
AESI 
Adverse events of special interest 
ALT 
Alanine aminotransferase 
AMD 
Age-related macular degeneration 
ANC 
Absolute neutrophil count 
ART 
Anti-retroviral therapy 
ASCT 
Autologous stem cell transplant 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration time curve 
BAL 
Bronchoalveolar lavage 
BCMA 
B-cell maturation antigen 
BCVA 
Best corrected visual acuity 
BM 
Bone marrow 
BMI 
Body mass index 
BOR 
Best Overall Response 
BOR 
Bortezomib 
Bor/Dex 
Bortezomib/Dexamethasone 
BSA 
Body surface area 
CAR-T 
Chimeric antigen T-cell therapy 
CBR 
Clinical Benefit Rate 
cfDNA 
Circulating plasma cell-free DNA 
CI 
Confidence interval 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
Creatine kinase 
Cmax 
Maximum plasma concentration 
CONSORT 
Consolidated Standards of Reporting Trials 
CPK 
Creatine phosphokinase 
CR 
Complete Response 
CRAB 
Myeloma-related syndrome characterized calcium elevation, renal 
failure, anemia, and bone lesions 
CRF 
Case Report Form 
CRR 
Complete Response Rate 
CSR 
Clinical study report 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTN 
Clinical Trial Notification 

 
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CV 
Cardiovascular 
CYP 
Cytochrome P 
Cys-
mcMMAF 
Cysteine maleimidocaproyl MMAF 
DILI 
Drug-induced liver injury 
DLT 
Dose Limiting Toxicity 
DNA 
Deoxyribonucleic acid 
DoR 
Duration of Response 
DREAMM 
Driving Excellence in Approaches to Multiple Myeloma 
DVT 
Deep vein thrombosis 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
eGFR 
Estimated glomerular filtration rate 
EMA 
European Medicines Agency 
EOI 
End of infusion 
EORTC 
European Organisation for Research and Treatment of Cancer 
EOT 
End of Treatment 
ESMO 
European Society for Medical Oncology 
FDA 
Food and Drug Administration 
FISH 
Fluorescence-in-situ hybridization 
FLC 
Free light chain 
FSH 
Follicle-stimulating hormone 
FTIH 
First-Time-in-Human 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GGT 
Gamma-glutamyl transferase 
HbcAb 
Hepatitis B core antibody 
HbsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HCG 
Human chorionic gonadotropin 
HCRU 
Health care resource utilization 
HCV 
Hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 
HRQOL 
Health-related quality of life 
HRT 
Hormone replacement therapy 
IA  
Interim analysis 
IB 
Investigator’s Brochure 
ICD 
Immunogenic cell death 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization of Technical Requirements 
for Pharmaceuticals for Human Use   
IDMC 
Independent Data Monitoring Committee 

 
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IEC 
Independent Ethics Committee 
IgG1 
Immunoglobulin G1 
IHC 
Immunohistochemistry 
IMiD 
Immunomodulatory drugs 
IMWG 
International Myeloma Working Group 
INR 
International normalization ratio 
IRB 
Institutional Review Board 
IRC 
Independent Review Committee 
IRR 
Infusion-related reaction 
IRT 
Interactive Response Technology 
ISS 
International Staging System 
ITT 
Intention-to-treat 
IV 
Intravenous 
KVA 
Keratopathy Visual Acuity 
LDH 
Lactate dehydrogenase 
LEN 
Lenalidomide 
LSFV 
Last Subject First Visit 
LVEF 
Left ventricular ejection fraction 
MCH 
Mean corpuscular hemoglobin 
MCV 
Mean corpuscular volume 
MDRD 
Modified Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Myocardial infarction 
MM 
Multiple myeloma 
MMAF 
Monomethyl auristatin-F 
MoA 
Mechanism of action 
MR 
Minimal Response 
MRD 
Minimal Residual Disease 
MRI 
Magnetic resonance imaging 
MSDS 
Material Safety Data Sheet 
MTD 
Maximum tolerated dose 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NGS 
Next-generation sequencing 
NOS 
Not otherwise specified 
NYHA 
New York Heart Association 
OATP 
Organic anion transporting polypeptides 
ORR 
Overall Response Rate 
OS 
Overall Survival 
OSDI 
Ocular Surface Disease Index 
PCR 
Polymerase chain reaction 
PD 
Progressive disease 
PET 
Positron emission tomography 
PFS 
Progression-free Survival 
PFS2 
Progression-free Survival on Subsequent Line of Therapy 
PFT 
Pulmonary function tests 

 
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P-gp 
P-glycoprotein 
PGIC 
Patient global impression of change 
PGIS 
Patient global impression of severity 
PI 
Proteasome inhibitors 
PK 
Pharmacokinetic(s) 
PO 
Per os (oral) 
POEMS 
Polyneuropathy, organomegaly, endocrinopathy, monoclonal 
plasmaproliferative disorder, skin changes 
PR 
Partial Response 
PRES 
Posterior reversible encephalopathy syndrome 
PRO 
Patient-reported outcome 
PTS 
Platform Technologies and Science 
QD 
Once daily 
QID 
Four times daily 
QLQ 
Quality of life questionnaire 
QoL 
Quality of life 
QT 
Q and T waves in ECG 
QTc 
Corrected QT interval 
QTcF 
Fridericia’s formula 
R-ISS 
Revised International Staging System 
RBC 
Red blood cell 
RMDOR 
Restricted mean duration of response 
RMST 
Restricted mean survival time 
RNA 
Ribonucleic acid 
RP2D 
Recommended Phase 2 dose 
RPLS 
Reversible posterior leukoencephalopathy syndrome 
RRMM 
Relapsed/Refractory multiple myeloma 
SAE 
Serious adverse event 
SADE 
Serious adverse device effect 
SAP 
Statistical Analysis Plan 
sBCMA 
Soluble BCMA 
SC 
Subcutaneous 
sCR 
Stringent Complete Response 
SCT 
Stem cell transplant 
SD 
Standard deviation of the mean 
SDV/SDR 
Source Data Verification/Source Document Review 
SoA 
Schedule of activities 
SoC 
Standard of care 
SOI 
Start of Infusion 
SPD 
Sum of the products of the maximal perpendicular diameters of 
measured lesions 
SPEP 
Serum protein electrophoresis 
SRM 
Study Reference Manual 
SRT 
Safety Review Team 
t1/2  
Serum half-life 
TLS 
Tumor lysis syndrome 

 
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tmax 
Time to maximum plasma concentration 
TNF 
Tumor necrosis factor 
TTBR 
Time to Best Response 
TTP 
Time to Disease Progression 
TTR 
Time to Response 
UK 
United Kingdom 
ULN 
Upper limit of normal 
USADE 
Unanticipated serious adverse device effect 
UPEP 
Urine protein electrophoresis 
USPI 
United States Product Information 
VGPR 
Very Good Partial Response 
VZIG 
Varicella zoster immune globulin 
WBC 
White blood cell 
WOCBP 
Woman of childbearing potential 
Definitions 
Term 
Definition 
Adverse Drug Reaction (ADR) 
An AE where a causal relationship between a medicinal product and the 
AE is at least a reasonable possibility, i.e., the relationship cannot be ruled 
out. 
 
In the context of a clinical trial, an ADR can be serious or nonserious. 
Serious ADRs may be subject to expedited reporting if they are considered 
unexpected (see SUSAR definition). 
 
For marketed products, ADRs are subject to expedited reporting within the 
country where they are authorized. 
AxMP 
Medicinal products used in the context of a clinical trial but not as IMPs, 
such as medicinal products used for background treatment, challenge 
agents, rescue medication, or used to assess endpoints in a clinical trial. 
AxMPs should not include concomitant medications, i.e., medications 
unrelated to the clinical trial and not relevant for the design of the clinical 
trial. 
 
Authorized AxMP = Medicinal product authorized in accordance with 
Regulation (EC) No 726/2004, or in any member state concerned in 
accordance with Directive 2001/83/EC, irrespective of changes to the 
labelling of the medicinal product. 
Note: Safety reporting with regard to authorized AxMPs shall be made in 
accordance with Chapter 3 of Title IX of Directive 2001/83/EC. 
 
Unauthorized AxMP = Medicinal product not authorized in accordance with 
Regulation (EC) No 726/2004 
Safety reporting for unauthorized AxMPs will follow the same processes 
and procedures as SUSAR safety reporting. 
Background treatment 
Type of medicinal product administered to each of the clinical trial 
participants, regardless of randomization group, to treat the indication that 
is the object of the study. Background treatment is generally considered to 
be the current standard of care for the particular indication. In these trials, 
the IMP is given in addition to the background treatment and 
safety/efficacy are assessed. The protocol may require that the IMP plus 
the background treatment is compared with an active comparator or with 
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Term 
Definition 
Challenge agent 
A product given to trial participants to produce a physiological response 
that is necessary before the pharmacological action of the IMP can be 
assessed. 
Co-administered product 
A product given to clinical trial participants as required by the protocol as 
part of their standard care for a condition that is not the indication for which 
the IMP is being tested and is therefore not part of the objective of the 
study. 
Comparator 
Any product used as a reference (including placebo, marketed product, 
GSK or non-GSK) for an investigational product being tested in a clinical 
trial. This is any product that is being used to assess the safety, efficacy, 
or other measurable value against the test product (IMP). 
Investigational Product (IMP) 
A pharmaceutical form of an active substance or placebo being tested or 
used as a reference in a clinical trial, including products already with a 
marketing authorization but used or assembled (formulated or packaged) 
in a way different from the authorized form, or when used for an 
unauthorized indication, or when used to gain further information about the 
authorized form. 
Medicinal products used to assess 
endpoints 
A product given to the participant in a clinical trial as a tool to assess a 
relevant clinical trial endpoint; it is not being tested or used as a reference 
in the clinical trial. 
Non-IMP 
Any products used in a clinical trial (other than the investigational product 
being tested) which are stipulated to be used to evaluate the efficacy and 
safety of the investigational drug in the protocol including comparators, 
co-administration drugs, rescue drugs, and premedication drugs. 
Non-IMPs products can be approved in Japan or other countries or can be 
products that are not approved. 
Placebo 
An inactive substance or treatment that looks the same as, and is given in 
the same way as, an active drug or intervention/treatment being studied. 
Rescue medication 
Medicine(s) identified in the protocol as those that may be administered to 
the participants when the efficacy of the IMP is not satisfactory, or the 
effect of the IMP is too great and is likely to cause a hazard to the 
participant, or to manage an emergency situation. 
Standard of care 
Medicine(s) for a specific indication, or a component of the standard care 
for a particular medical indication, based on national and/or international 
consensus; there is no regulatory significance to this term. 
Products/regimens considered standard of care may differ country to 
country, depending on consensus in individual countries. 
SUSAR 
In a clinical trial, a serious adverse reaction that is considered unexpected, 
i.e., the nature or severity of which is not consistent with the reference 
safety information (e.g., IB for an unapproved IMP). All ADRs that are both 
serious and unexpected are subject to expedited reporting. 

 
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Trademark Information 
 
Trademarks of the GSK group of 
companies 
 
Trademarks not owned by the GSK group 
of companies 
Blenrep 
 
Darzalex 
None 
 
Kyprolis 
None 
 
MedDRA 
None 
 
RandALL NG 
None 
 
Velcade 

 
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10.15. 
Appendix 15: Home Healthcare and Telemedicine 
Approaches 
Home Healthcare (General Visit) 
Where applicable country and local regulations and infrastructure allow, home healthcare 
may be permitted. Home healthcare is defined as a remote visit(s) that is/are performed at 
the participant’s home by qualified personnel (e.g. nurse).   
Activities that may be done as part of a home healthcare visit must follow the schedule 
provided in the SoA (Section 1.3) and include:  
• Collection of blood and urine samples including:  
▪ Safety assessments which may include routine blood and urine 
sampling 
▪ PK and ADA specimen collection 
▪ Efficacy assessments to be sent to central lab 
▪ Biomarker, immunogenicity and genetic assessments 
▪ Pregnancy tests 
▪ 12-Lead ECG 
 
Note:  Biological samples should not be collected if they cannot be 
processed in a timely manner or appropriately stored until their 
intended use. Please refer to the SRM/lab manual for sample collection 
and storage requirements. 
• Measurement of vital signs (BP, heart rate, body temperature) and weight. 
• Physical examination 
• Administration of study drug (subcutaneous delivery only, no infusions). 
• Administration of pre/post-medication 
• Identification and reporting of concomitant medications. 
• Dosing diary review for medication compliance. 
• Identification and reporting of AEs/SAEs. 
Note: The investigator or other qualified medical professional must ensure 
reporting of AEs and SAEs is completed in accordance with the protocol 
and applicable regulations and that the appropriate medical intervention, 
therapeutic intervention, and/or support measures are instituted, as 
necessary.  
The participant should be informed of any potential risks associated with Home 
Healthcare and sign a revised Informed Consent Form if required. IRB/Ethics committee 
should be informed and/or approve of this change in approach and the process 
documented in study files. 
Home Healthcare (Ophthalmologic Exam) 
Where applicable country and local regulations and infrastructure allow, protocol-
required eye exams may be done in the participant’s home or specified alternative eye 

 
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care specialist clinic. Activities that may be done as part of in-home eye exams must 
follow the schedule provided in the SoA (Section 1.3) and include:  
• Visual Acuity (VA) by near-chart VA or pinhole. 
• Slit lamp exam  
• Tonometry   
• Ophthalmoscopy   
The participant should be informed of any potential risks associated with Home 
Healthcare Ophthalmologic exams and sign a revised Informed Consent Form if required. 
IRB/Ethics committee should be informed and/or approve of this change in approach and 
the process documented in study files. 
Telemedicine 
Where applicable country and local regulations and infrastructure allow, telemedicine 
visits may be permitted. Telemedicine visits are defined as online (virtual) visits which 
will use secure video conference, phone calls, a web portal and/or mobile application as a 
way of communicating with and monitoring the participant’s progress. Telemedicine 
visits are conducted by an investigator or other qualified medical professional and may be 
done in combination with visits from Home Healthcare personnel (see above). 
Activities that may be done as part of a telemedicine visit include: 
• Medical evaluation of the participant  
• Identification and reporting of concomitant medications. 
• Dosing diary review for medication compliance. 
• Identification, management, and reporting of AEs and SAEs.  
 
Note: The investigator or other qualified medical professional must ensure 
reporting of AEs and SAEs is completed in accordance with the protocol 
and applicable regulations and that the appropriate medical intervention, 
therapeutic intervention, and/or support measures are instituted, as 
necessary. Participants utilizing telemedicine can report AEs at any time 
via an app, phone call or videoconference with site staff. 
The participant should be informed of any potential risks associated with the virtual 
medium and sign a revised Informed Consent Form if required. IRB/Ethics committee 
should be informed and/or approve of this change in approach and the process 
documented in study files. 
Remote Patient Reported Outcomes (PRO) Administration 
Where applicable country and local regulations and infrastructure allow, remote PRO 
administration may be permitted. Remote PRO administration is defined administration 
of protocol PROs by a qualified third party over the telephone. The remote PRO 
Administrator will use the versions of the PROs designed for verbal administration. The 

 
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remote PRO Administrator will have access to the electronic PRO portal for the study 
and input participant responses as the interview is being conducted.  
The participant should be informed of any potential risks associated with the remote PRO 
administration and sign a revised Informed Consent Form if required. IRB/Ethics 
committee should be informed and/or approve of this change in approach and the process 
documented in study files. 
 

 
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10.16. 
Appendix 16: Data Management/Monitoring 
Source Data Verification/Source Document Review (SDV/SDR) 
During periods in which on-site monitoring is not permitted, GSK will consider remote 
Source Data Verification/Source Document Review (SDV/SDR) where permitted by the 
clinical site/institution and in accordance to with local law and regulatory guidance 
documents. 
Remote SDV/SDR will be proposed to study sites to meet a patient and/or critical data 
quality need, e.g., to assess patient safety or to ensure data integrity.  The study specific 
monitoring plan will be updated in accordance with remote monitoring practices adopted 
for the country/study. The subject informed consent will be updated in line with local 
regulations to permit remote monitoring practices. In case of remote SDV/SDR, GSK 
will work with the site to ensure subject privacy. 
 
eCRF/CRF Final or Interim Sign off Process:  
The Principal Investigator (PI) is responsible for ensuring that the data within the eCRF 
casebook and any other data sources utilized during the study for each study patient is 
complete and consistent with source documents throughout the study (ICH GCP 4.9.1 
and 4.9.2). The PI may sign/re-sign the eCRF from any computer/location by accessing 
the eDC platform) using his/her unique eCRF login credentials.  
 
Essential Document Sign Off Process:  
If an investigator is unable to print and sign essential documents such as 
Protocol/Amendment signature page then Email approval can be accepted by replying to 
the relevant email that is sent by GSK. Please note that unblinding procedures remain the 
same as those documented in the protocol and other study-related documents. 
 

 
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10.17. 
Appendix 17: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for this amendment is located 
directly before the Table of Contents (TOC). 
Amendment 6: 03 Oct 2023 
Where this Protocol Amendment applies: 
Protocol Amendment 6 JPN-1 applies to all participants and all sites in Japan. 
Overall Rationale for the current amendment:  
This protocol has been amended to update the number of PFS events required to trigger 
the primary PFS analysis and to include an interim analysis for PFS at
% information 
fraction. The updates allow for a longer duration of follow up and increasing OS data 
maturity at the time of Primary PFS analysis. The addition of an interim analysis allows 
the opportunity to test for efficacy as well. 
This amendment has also been updated to incorporate an additional sensitivity analysis 
for conventional DoR using investigator-assess response in the statistical analysis section, 
an update of the terminology from Reporting and Analysis Plan” (RAP) to “Statistical 
Analysis Plan” (SAP), and a modified multiplicity strategy as well as changes to the 
targeted overall survival hazard ratio assumption within the sample size determination 
section. Additional details regarding planned OS interim analyses and OS sample size 
assumptions have been included. 
The statistical considerations for the Japan Expansion Cohort have been updated to 
clarify the conditions under which the statistical analyses for the Japan Expansion Cohort 
will be conducted. 
An update to urine immunofixation requirements in the schedule of activities has been 
made. Additional administrative changes have been made including correction of an 
administrative numbering error in the inclusion and exclusion criteria and clarification of 
data collection for overall survival. 
List of main changes in the protocol and their rationale: 
Section # and title 
Description of change 
Brief rationale 
Throughout the document 
Reporting and analysis Plan (RAP) 
updated to Statistical Analysis Plan (SAP) 
 
Updated Investigator Brochure version 
 
Minor typographical corrections 
In alignment with GSK naming and 
style conventions 
 
 
Section 1.3 Schedule of 
Activities 
Clarification on survival data collection in 
Table 1 and Table 2  
Added clarity on the overall survival 
data collection 
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Section # and title 
Description of change 
Brief rationale 
Section 1.3 Schedule of 
Activities 
Added wording to indicate urine 
immunofixation must be performed each 
time M-protein is not quantifiable by 
UPEP (0 mg/24 hr) AND SPEP (0 g/dL) 
 
A urine immunofixation result is 
required with a serum 
immunofixation result for sCR, CR 
and VGPR response, as per IMWG 
2016 criteria. It is not required 
alone. 
Section 2.3.1 Summary of Risk 
Assessment for Belantamab 
Mafodotin (Treatment Arm A), 
Daratumumab (Treatment Arm 
B), and Bor/Dex (Treatment 
Arms A and B) 
Updates to potential overlapping toxicities 
and the risks related to belantamab 
mafodotin. 
To provide the most up to date 
information in alignment with IB 
v11. 
Section 3 Objectives and 
Endpoints and Section 9.5.1 
Efficacy Analyses 
OS bullet moved up. 
Moved up for consistency with 
other DREAMM-7 study 
documents. 
Section 4.2 Scientific Rationale 
for Study Design 
Addition of interim analysis. 
The addition of an interim analysis 
allows the opportunity to test for 
efficacy prior to the primary 
analysis. 
Section 5.1 Inclusion Criteria 
Numbering of the last 2 inclusion criterion 
has been changed from 1 and 2 to 10 
and 11 to continue numbering from the 
previously listed inclusion criteria. 
To correct a numbering error. 
Section 5.2 Exclusion Criteria 
Numbering has been changed to begin 
from 1, instead of continuing on from 
inclusion crtieria numbering. 
To correct a numbering error. 
Section 7.1 Discontinuation of 
Study Intervention 
Clarification on survival data collection. 
Added clarity on the overall survival 
data collection 
Section 9.1 Statistical 
Hypotheses 
Section focused on hypotheses to be 
tested only. Removed reference to 
statistical assumptions and significance 
level for testing. Reordered endpoints to 
align with multiplicity strategy.  
The inclusion of an interim analysis 
changes the multiplicity strategy, 
details were previously included in 
multiple places and are more 
appropriate to include in 
Section 9.2 and Section 9.3. 
Section 9.2 Multiple 
Comparisons and Multiplicity 
Modified multiplicity strategy, 
acknowledging the importance of OS as a 
key secondary endpoint and 
accommodating the group sequential 
design. Further details to be provided in 
the SAP.  
Inclusion of interim analyses and 
modified multiplicity strategy.  
Section 9.3 Sample Size 
Determination 
Update to the number of PFS events  
needed for the Primary PFS Analysis 
from
To align with the addition of an 
interim analysis for efficacy. 
Section 9.3 Sample Size 
Determination 
Primary Endpoint PFS: changed wording 
of “progression” to “progression or death”. 
Added clarity onto the definition of 
progression-free survival within the 
sentence. 
Section 9.3 Sample Size 
Determination 
Subsections for key secondary endpoints 
removed.   
To permit a longer follow up, 
increase OS data maturity at the 
time of Primary PFS analysis/IA2 
and account for PFS interim 
analysis for efficacy (IA1). 
Subsections for key secondary 
endpoints provided no additional 
value.   
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Section # and title 
Description of change 
Brief rationale 
Section 9.3 Sample Size 
Determination 
Subsection for Japan Expansion Cohort 
has been updated to state the conditions 
under which the analysis for Japan 
expansion cohort wil be conducted. 
To specify the conditions for 
analysis of the Japan Expansion 
cohort given the addition of an 
interim analysis for efficacy. 
Section 9.5.1 Efficacy Analyses 
Added sentence defining an additional 
sensitivity analysis that may be 
performed. 
 
  
Additional statistical analysis that 
may be performed depending on 
IRC concordance. 
Section 9.5.1 Efficacy Analyses 
Removed reference to significance level 
for testing and added clarification of p-
values and confidence intervals to be 
produced.  
 
Multiplicity strategy is defined in 
Section 9.2 and will be clarified in 
the SAP.  
Section 9.6.1 Periodic IDMC 
Safety Reviews and CPMS 
Early Access  
Section restructured and multiple interim 
analyses considered for IDMC review.  
Addition of interim analyses for 
efficacy.  
Section 9.6.1 Periodic IDMC 
Safety Reviews and CPMS 
Early Access  
Added clarification that potential 
delegate(s) not involved in the study 
conduct may be unblinded for performing 
population PK and PKPD dataset 
preparation in support of planned 
analyses and PK display review. All other 
personnel will remain blinded to 
aggregate data by treatment group until 
database lock. 
To allow for sufficient time to 
prepare and conduct planned 
analyses. 
Section 9.6.2 Interim Analysis 
Interim analyses for efficacy included.  
Tables of Stopping Boundaries for Interim 
Analysis for PFS Efficacy added.  
Additional OS analyses considered.  
  
Interim analyses added to allow the 
opportunity to test for efficacy 
early.  
If requested, additional OS 
analyses may be required.  
Section 9.6.4 Final Analysis 
Interim analyses for efficacy included.  
Primary PFS analysis/IA2 and final 
analysis events and timing modified.   
 
Interim analyses added to allow the 
opportunity to test for efficacy 
early.  
Primary PFS analysis/IA2 and final 
analysis events and timing modified 
to permit a longer follow up and 
increase OS data maturity.  
Section 10.1.11 Third parties 
and Sub-Contractors 
Alliance Pharma has been changed to 
Resolian Bioanalytics (name change 
only) 
Alliance Pharma Inc. is now doing 
business as Resolian Bioanalytics 
Section 10.14 Appendix 14: 
Abbreviations and Trademarks 
Updated abbreviations list 
Inclusion of IA and SAP; removal of 
RAP 
 
Amendment 5 JPN-1: 23 Feb 2023 
Where this Protocol Amendment applies: 
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Overall Rationale for the current amendment: 
This protocol has been amended to remove the interim analysis for futility and superiority 
that was planned at
% information. Enrollment was completed for the Intent-To-Treat 
population in June 2021 and safety data is continuing to be reviewed periodically with the 
Independent Data Monitoring Committee (IDMC) every 
 The IDMC has not 
noted any new/significant safety signals for the study to date. 
The protocol has also been amended to introduce an Independent Review Committee 
(IRC) and to document that the analysis of efficacy endpoints will be based on 
assessments determined by an IRC instead of derived confirmed response based on an 
algorithm. In addition, Duration of Response and Overall Survival, which were secondary 
endpoints for the study, have now been classified as key secondary endpoints. Additional 
changes have been incorporated to align with program-level and protocol template 
updates. 
List of main changes in the protocol and their rationale: 
Section # and title 
Description of change 
Brief rationale 
Section 1.3 Schedule of 
Activities (SoA) 
Table 1: Edit to footnote 4 on when 
participants may have their 
ophthalmologic exams decreased to once 
every 3 months to add “or prior to” the 
time of the sixth dose exam. 
 
Table 1 and Table 2: Added footnote 7 on 
collection of OS data. 
 
Table 2: Added ocular exam to be 
performed at Fixed Visits. Edit to footnote 
4 on timing of ocular exams. 
 
Table 3: Edit to footnote f to add a 
1 month window for follow-up MRD 
testing. 
For clarification. 
 
 
 
 
 
To ensure data integrity for the OS 
endpoint. 
 
For clarification. 
 
 
 
For clarification. 
Section 2.2.4 Clinical 
Experience with Belantamab 
Mafodotin 
Updated with results from the final 
analysis for Study 205678 (DREAMM-2). 
To provide the most up to date 
information. 
Section 2.3.1 Summary of Risk 
Assessment for Belantamab 
Mafodotin (Treatment Arm A), 
Daratumumab (Treatment 
Arm B), and Bor/Dex 
(Treatment Arms A and B) 
Updates to potential overlapping toxicities 
and the risks related to belantamab 
mafodotin. 
To provide the most up to date 
information. 
Section 3 Objectives and 
Endpoints 
The efficacy endpoint of OS has been 
changed from a secondary endpoint to a 
key secondary endpoint. 
To enable formal statistical testing. 
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Section # and title 
Description of change 
Brief rationale 
Section 3 Objectives and 
Endpoints 
The efficacy endpoint of DoR has been 
changed from a secondary endpoint to a 
key secondary endpoint; updated testing 
hierarchy; changed DoR definition to 
include all participants regardless of 
response status (not just based on 
responder) and updated primary analysis 
method for DoR to be based on a 
comparison of the restricted mean DoR 
(RMDOR) between the treatment arms. 
To enable an ITT analysis using all 
participants (responders and non-
responders) with increased 
sensitivity and to account for the 
expected difference in the 
proportion of responders between 
the treatment arms so that valid 
statistical comparisons can be 
made. 
Section 3 Objectives and 
Endpoints 
Deleted “total monoclonal antibody” from 
the exposure and pharmacokinetic 
endpoints. 
Based on adequacy of 
understanding of exposure-
response relationship from previous 
belantamab mafodotin studies. 
Section 3 Objectives and 
Endpoints 
Updated wording of PRO-CTCAE 
endpoint. 
To align with the wording of this 
endpoint in the program. 
Section 3 Objectives and 
Endpoints 
Footnote number 1 added to clarify that 
all disease response categories will be 
determined by an IRC. 
For clarification. 
Section 4.1 Overall Design 
Added information on collection of 
survival data outside of the protocol 
window noted in the SoA. 
To ensure data integrity for the OS 
endpoint. 
Section 4.2 Scientific Rationale 
for Study Design 
Added paragraph on data that will be 
used by the IRC to determine disease 
response. 
 
Deleted text on interim analysis from final 
paragraph. 
For clarification. 
 
 
 
To align with the removal of the 
interim analysis. 
Section 4.4 End of Study 
Definition 
Deletion of the Japan-specific end of 
study definition. 
The global end of study definition is 
applicable for the Japan expansion 
cohort. 
Section 6.1.3.2 Corneal 
Supportive Care Guidelines and 
Section 8.2.6.1 Treatment 
Arm A 
Edit to text on when participants may 
have their ophthalmologic exams 
decreased to once every 3 months to add 
“or prior to” the time of the sixth dose 
exam. 
For clarification. 
Section 6.5.1 Permitted 
Concomitant Therapies 
Added that use of approved monoclonal 
antibody treatments for serious conditions 
unrelated to multiple myeloma must be 
discussed with the GSK Medical Monitor. 
To enable participants to receive 
monoclonal antibody treatments for 
serious conditions unrelated to MM 
during the study 
Section 6.6.1 Belantamab 
Mafodotin 
Updates to the dose modification 
guidelines for AEs associated with 
belantamab mafodotin based on serum 
creatinine and albumin/creatinine ratios. 
To align with program-level update. 
Section 7.1 Discontinuation of 
Study Intervention 
Added information on follow-up for 
survival to the end of study regardless of 
whether the participant has discontinued 
study intervention. Added information on 
modified follow-up if the participant does 
not agree to continue in-person visits. 
To ensure data integrity for the OS 
endpoint. 
Section 7.3 Lost to Follow Up 
Added information on the collection of 
vital status of randomized participants. 
To ensure data integrity for the OS 
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Section # and title 
Description of change 
Brief rationale 
Section 8.1.1 Response 
Evaluation 
An IRC has been added to assess 
efficacy endpoints. Derivation of 
response via a proprietary algorithm has 
been deleted. 
To address health authority 
feedback received on another study 
in the program that the algorithm is 
not validated and therefore cannot 
be used as the primary analysis of 
efficacy endpoints. 
Section 8 Study Assessments 
and Procedures Table 19 and 
Section 8.2.5 Clinical Safety 
Laboratory Assessments 
Removed request for participants with 
elevations of LDH, CK and/or AST to 
have samples tested centrally for CK and 
LDH isoenzyme levels if possible. 
Potential for Other Laboratory 
Abnormalities removed with risk 
table update. 
Section 8.2.6.2 Treatment 
Arm B 
Edit to wording on timing of ocular exams 
to add a ±4 week window for 6 monthly 
eye exams. 
For clarification. 
Section 8.5.1 Belantamab 
Mafodotin Blood Sample 
Collection for Pharmacokinetics 
and Section 8.5.2 Belantamab 
Mafodotin PK Sample Analysis 
Updated to make analysis of total 
monoclonal antibody optional. 
Based on adequacy of 
understanding of PK and exposure-
response relationship from previous 
belantamab mafodotin studies PK 
sampling for each ADA sample is 
not needed due to the drug 
tolerance of the immunogenicity 
assays. 
Section 8.6 Belantamab 
Mafodotin Immunogenicity 
Deleted analysis of belantamab 
mafodotin plasma concentration for ADA 
samples. 
 
 
Added statement on ADA sample 
collection. 
Drug concentration is not needed 
for interpretation of ADA data due 
to the high drug tolerance of the 
immunogenicity assays. 
 
To allow reducing and termination 
of ADA sample collection when 
clinical data of immunogeniticity 
within and cross studies are 
deemed sufficient. 
Section 9.1 Statistical 
Hypotheses 
Statistical hypotheses that will be tested 
for DoR and OS have been added. 
To support addition of DoR and OS 
as key secondary endpoints. 
Section 9.1.1 Multiple 
Comparisons and Multiplicity 
Deleted text on the interim analysis. 
 
Updates to the hierarchical testing 
procedure to add DoR and OS as key 
secondary endpoints. 
To align with the removal of the 
interim analysis. 
To support addition of DoR and OS 
as key secondary endpoints. 
Section 9.2 Sample Size 
Determination 
Updates to the power calculation and 
target PFS events based on the removal 
of the interim analysis. 
 
Added option to perform interim analyses 
of the Japan expansion cohort before 
14 PFS events have been documented. 
 
 
Added information on sample size 
determination for DoR and OS as key 
secondary endpoints. 
To align with the removal of the 
interim analysis. 
 
 
To enable Japan-specific interim 
analyses to be performed if 
required by local regulatory 
agencies. 
 
To support addition of DoR and OS 
as key secondary endpoints. 

 
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Section # and title 
Description of change 
Brief rationale 
Section 9.4.1 Efficacy Analyses 
Analysis of efficacy endpoints will be 
based on IRC-assessed response 
instead of derived response. 
 
Added definition of North East Asia as 
consisting of Japan, China and Republic 
of Korea. 
 
Addition of statistical analysis methods 
for DoR and OS as key secondary 
endpoints. 
 
Addition of statistical analysis methods 
for imaging plus MRD negativity. 
To align with addition of an IRC. 
 
 
 
For clarity based on ICH E17 
guidelines. 
 
 
To support addition of DoR and OS 
as key secondary endpoints. 
 
Had been missed inadvertanely in 
previous versions of the protocol. 
Section 9.4.3 Pharmacokinetic 
Analyses 
Updated to make analysis of total 
monoclonal antibody optional. 
Based on adequacy of 
understanding of PK and exposure-
response relationship from previous 
belantamab mafodotin studies. 
Section 9.5 Interim Analyses 
Deleted text on the interim analysis for 
futility and superiority. Changed section 
heading to “Planned Analyses” and 
created sub-headings. 
To align with the removal of the 
interim analysis and clarification on 
the planned analyses. 
Section 10.1.4 Data Protection 
Addition of text around protection of 
personal data of the investigator and site 
staff, responsibilities of the parties related 
to data protection, and information 
technology systems used to collect, 
process and store study-related data. 
To align with updates to the 
protocol template on data 
protection. 
Section 10.1.5 Committees 
Structure 
Addition of information on the SRT & IRC. 
To align with addition of an IRC. 
Section 10.1.11 Appendix 1: 
Regulatory, Ethical, and Study 
Oversight Consideration 
Addition of Section 10.1.11 listing all third 
parties and sub-contractors used in the 
study. 
For transparency. 
Section 10.11 Appendix 11: 
Progression-Free Survival 
Event and Censoring Rule 
Update to table and footnotes. 
For clarification of PFS censoring 
rules. 
 
 
 
Amendment 4 JPN-1 01 Sep 2022 
Where this Protocol Amendment applies: 
Protocol Amendment 4 JPN-1 applies to all participants and all sites in Japan. The 
changes made in this current amendment were the same changes made in the global 
protocol amendment 4 except for the country specific requirements described in 
Appendix 18. 

 
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Overall Rationale for Amendment 4 JPN-1: 
This protocol has been amended to update the statistical analyses to include Clinical 
Benefit Rate (CBR) as a secondary endpoint and Sustained MRD negativity rate as an 
exploratory endpoint. The Key Secondary Endpoint of MRD Negativity has been 
clarified to state that the analysis will conducted in participants with CR or better, and a 
sensitivity analysis will be conducted in patients with a best overall response of VGPR. 
The definition for MRD negativity has been updated to state that participants in the ITT 
population without MRD assessment will be treated as non-negative MRD.These updates 
clarify how endpoints will be analyzed and will allow for further assessment of clinical 
activity and characterization of efficacy. 
In addition, the term “anti-cancer therapy” has been updated to state “anti-myeloma 
therapy” in the Prohibited Concomitant Therapies Section and where relevant throughout 
the protocol document. This clarifies the intent that “anti-cancer therapy” should be 
specifically limited to therapies directed against multiple myeloma and those therapies 
that have anti-myeloma properties.” 
Additional changes were incorporated which align with program revisions and/or updates 
as listed in table below. 

 
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Section # and Name 
Description of Change 
Brief Rationale  
Section 1.1 Synopsis 
 
 
 
Updated to include - Clinical 
Benefit Rate (CBR) as a 
Secondary Endpoint. The 
definition for Duration of 
Response (DoR) has been 
updated to include death due 
to any cause. 
Reduced total number of 
Japanese participants from
to
CBR is an additional method of 
assessment of clinical activity to further 
characterize efficacy. The definition for 
DoR has been updated to be consistent 
with regulatory guidance regarding the 
endpoint. 
Based on actual recruitment status in 
Japan, the total number of Japanese 
participants has been updated. 
Section 1.3 Schedule of Activities, 
Table 1 and Table 2 
Updated to clarify the 
requirements for PFS follow-up 
as well as timing of Serum and 
Urine Immunofixation testing.  
Update improves readability and 
removes ambiguity when specifying the 
protocol requirements for PFS follow-up 
and immunofixation testing. 
Section 2.3.1.Summary of Risk 
Assessment for Belantamab 
Mafodotin (Treatment Arm A), 
Daratumumab (Treatment Arm B), 
and Bor/Dex (Treatment Arms A and 
B) 
The Risk Assessment table 
been amended to be consistent 
with clarifications and updates 
made in the most current 
version of the belantamab 
mafodotin Investigator 
Brochure (v10.0). 
To align protocol language with the 
updates in the most current version of 
the belantamab mafodotin Investigator 
Brochure (v10.0). 
Section 3 Objectives and Endpoints 
Updated to include Secondary 
endpoint of Clinical Benefit 
Rate (CBR) and Exploratory 
Endpoint of Sustained MRD 
negativity rate. The definition 
for Duration of Response 
(DoR) has been updated to 
include death due to any 
cause.  
CBR is an additional method of 
assessment of clinical activity to further 
characterize efficacy. 
MRD is recognized as a dynamic 
indicator that requires consistent 
monitoring before MRD utility is fully 
defined, and sustained MRD negativity 
is a significant prognostic factor. 
The definition for DoR has been 
updated to be consistent with regulatory 
guidance regarding the endpoint.  
Section 6.1.4.4 Interference with 
Serum Protein Electrophoresis and 
Immunofixation Tests 
Updated to clarify the 
requirements for performing 
daratumumab-IFE assay 
Update improves readability when 
specifying the protocol requirements for 
performing assay. 
Section 6.5.1 Permitted Concomitant 
Therapies 
Updated to include text 
regarding therapy for unrelated 
malignancies. 
Clarification that patients with an 
unrelated second malignancy may 
remain on study if the malignancy may 
be addressed by localized therapy.  
Section 6.5.2 Prohibited Concomitant 
Therapies 
Updated to specify “anti-
myeloma therapy” in place of 
“anti-cancer therapy”. 
Clarification that prohibited therapy is 
specific to therapy for multiple 
myeloma. 
Section 6.6 Dose Modification and 
Delay 
Updated to specify that Medical 
Monitor should be contacted 
prior to restarting therapy for 
patients with dose 
delays/interruptions longer than 
42 days. 
Provide specific guidance that sites 
should contact the Medical Monitor 
prior to restarting therapy following 
significant dosing delays in order to 
protect patient safety and study 
integrity.  
Section 6.6.5 Guidance on Dose 
Delays for Treatment Arm A and B 
Updated to further clarify the 
definition of a cycle of study 
treatment.  
Clarification provides explicit guidance 
on what is considered to be the start of 
a cycle and that if no therapy is given.  
Section 6.7 Intervention After the End 
of the Study 
This Section has been updated 
to clarify that no further 
interventions will occur after 
the End of Study (final OS 
analysis).  
Clarification provides an explicit 
statement regarding interventions 
following the End of Study (final OS 
analysis).  
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Section # and Name 
Description of Change 
Brief Rationale  
Section 7.1 Discontinuation of Study 
Intervention 
Updated to require that the 
Medical Monitor be contacted 
to review disease assessments 
and confirm disease 
progression prior to participant 
discontinuation for Progressive 
Disease. 
Provide guidance that sites should 
contact the Medical Monitor to confirm 
that suspected Progressive Disease 
meets IMWG criteria in order to prevent 
patients from being prematurely 
discontinued from study treatment in 
the instance that the reason for 
discontinuation is specifically limited to 
disease progression.  
Section 8.1.3 MRD Assessment and 
PET-CT Imaging 
Updated to clarify the timing for 
initial and subsequent MRD 
testing.  
Clarification provides more detail in 
specifying the timing of initial MRD 
testing and when to perform 
subsequent testing.  
Section 8.5.1 Belantamab Mafodotin 
Blood Sample Collection for 
Pharmacokinetics 
Added clarification that PK and 
accompanying sBCMA sample 
collection may be terminated 
when sufficient data have been 
collected. 
Clarification informs sites that PK 
collection may be terminated when 
sufficient data has been collected, thus 
reducing the burden on study 
participants and study sites.  
Section 8.9.1 Soluble BCMA 
Updated to remove 
requirement for sBCMA sample 
collection independent from PK 
samples and dosing at fixed 
timepoints.  
Biomarker sample collection will not be 
required at additional timepoints 
beyond those for PK and dosing at 
fixed timepoints as these samples are 
no longer needed to characterize 
sBCMA activity.   
Section 9.2 Sample Size 
Determination 
Reduced total number of 
Japanese participants from 
to
total number of Japan 
expansion cohort participants 
from
and required 
progression-free survival (PFS) 
events in Japan expansion 
cohort from 
Based on actual recruitment status in 
Japan, the total number of Japanese 
participants and Japan expansion 
cohort participants has been updated. 
Section 9.4.1 Efficacy Analyses, 
Table 25 
Updated to include Secondary 
endpoint of Clinical Benefit 
Rate (CBR) and Exploratory 
Endpoints of Sustained MRD 
negativity rate, Time To Best 
Response (TTBR) and VGPR 
rate. The definition for Duration 
of Response (DoR) has been 
updated to include death due 
to any cause. The definition for 
MRD negativity rate has been 
updated as well.  
CBR is an additional method of 
assessment of clinical activity to further 
characterize efficacy. 
MRD is recognized as a dynamic 
indicator that requires consistent 
monitoring before MRD utility is fully 
defined, and sustained MRD negativity 
is a significant prognostic factor. 
TTBR and VGPR rate were already 
included in Section 3.3 Objectives and 
have been added in Section 9.4.1 for 
consistency.  
Section 9.6 Final Analyses 
Section 9.6 has been added to 
clarify the timing of the final OS 
analyses and that this analyses 
will coincide with the End of 
Study.  
The addional text provides specific 
detail around the timing of the final OS 
analysis and confirms it will coincide 
with the End of Study. 
 
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Amendment 03 JPN-1: 29-SEP-2021  
Where this Protocol Amendment applies: 
Protocol Amendment 03 JPN-1 applies to all participants and all sites in Japan. The 
changes made in this current amendment were the same changes made in the global 
protocol amendment 03 except for the country specific requirements described in 
Appendix 18. 
Overall Rationale for the Amendment 03 JPN-1:  
The protocol has been amended to remove the first of two interim analyses that were 
planned for the 207503 study. The first interim analysis is based on
% of progression-
free survival (PFS) events, allowing for early stopping due to harm (inferior efficacy), 
and the second interim analysis is based on
% of PFS events, allowing for early 
stopping due to futility or efficacy. In addition, safety data is being reviewed periodically 
starting from when 
 and then every  
or as requested by the Independent Data Monitoring Committee (IDMC) 
thereafter. The first interim analysis was removed as the trial has accrued faster than 
anticipated and completed enrolment well in advance of the estimated date for the first 
interim analysis.  
Safety data will continue to be reviewed periodically every 
 and the interim 
analysis based on
% of PFS events will be performed as planned. 
Additional changes were incorporated which align with program revisions and/or updates 
as listed in table below.   
Original Section/Table/Figure 
Description of Change 
Brief Rationale 
Section1.3 Schedule of Activities 
Updated Footnote 15 in the 
Arm A Schedule of Activities to 
specify imaging should be 
retained at the clinical study 
site. 
Imaging should be retained at the 
clinical study site to be available if 
needed for analysis rather than being 
stored at a central vendor. 
Updated Footnote 17 in the 
Arm B Schedule of Activities to 
specify imaging should be 
retained at the clinical study 
site. 
Imaging should be retained at the 
clinical study site to be available if 
needed for analysis rather than being 
stored at a central vendor. 
Section2.2.4.2 Pharmacokinetics and 
Pharmacodynamics in Humans 
Background information has 
been amended to be consistent 
with clarifications and updates 
made in the most current 
version of the Investigator 
Brochure (v9.0).  
To align language with the most current 
version of the Investigator Brochure 
(v9.0). 
Section 4.2 Scientific Rationale for 
Study Design 
Text has been updated to 
specify a single interim 
analysis will be performed.  
Interim analysis for harm (inferior 
efficacy), based o
% of PFS 
events has been removed due to faster 
than anticipated accrual and completion 
of enrolment well in advance of the 
estimated date for the first interim 
analysis. 
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Original Section/Table/Figure 
Description of Change 
Brief Rationale 
Section 6.6.5 Guidance on Dose 
Delays for Treatment Arm A and B, 
Table 16, Table 17 
Text in Row 3 of Table 16 & 
Table 17 has been updated 
from “…bortezomib >21 days” 
to “…bortezomib ≤21 days” 
Text in Row 4 of Table 16 & 
Table 17 has been updated 
from “…bortezomib <21 days” 
to “…bortezomib >21 days” 
This change corrects a typographical 
error in Table 16 and Table 17.  
Section 9.1.1 Multiple Comparisons 
and Multiplicity  
Text has been updated to 
specify a single interim 
analysis will be performed. 
References to the interim 
analysis for harm (inferior 
efficacy) have been removed. 
Interim analysis for harm (inferior 
efficacy), based on
% of PFS 
events has been removed due to faster 
than anticipated accrual and completion 
of enrolment well in advance of the 
estimated date for the first interim 
analysis. 
Section 9.2 Sample Size 
Determination 
The number of PFS events 
needed to trigger Primary 
Endpoint analysis has been 
updated from 
 
The reference to the software 
package used for calculation of 
the Key Secondary Endpoint: 
Minimal Residual Disease 
(MRD) Negativity has been 
updated from East 6.4  to 
PASS 2019, v19.0.1 
The required number of PFS events to 
trigger Primary Endpoint analysis has 
been recalculated as a result of the 
removal of the first interim analysis.  
The software package used for the 
calculation of the Stopping Boundaries 
for the Key Secondary Endpoint: MRD 
Negativity has been updated to allow 
for a more precise estimate.  
Section 9.4.1 Efficacy Analyses, 
Table 25 
The number of PFS events 
needed to trigger Primary 
Endpoint analysis has been 
updated from 
 
The required number of PFS events 
has been recalculated as a result of 
removing the first interim analysis. 
Section 9.5 Interim Analyses, Table 
27, Table 28 
Text has been updated to 
specify a single interim 
analysis will be performed. 
References to the interim 
analysis for harm (inferior 
efficacy) have been removed. 
The number of PFS events 
needed to trigger the interim 
analysis for futility and 
superiority has been updated 
from 
 
The Stopping Boundaries for 
PFS Interim Analyses (Table 
28) have been recalculated. 
Interim analysis for harm (inferior 
efficacy), based on
% of PFS 
events has been removed due to faster 
than anticipated accrual and completion 
of enrolment well in advance of the 
estimated date for the first interim 
analysis. 
The required number of PFS events to 
trigger Primary Endpoint analysis has 
been recalculated as a result of the 
removal of the first interim analysis. 
 
Section 9.5 Interim Analyses Table 29 
The Stopping Boundaries for  
MRD Negativity (Table 29) 
have been recalculated. 
The software package used for the 
calculation of the Stopping Boundaries 
for the Key Secondary Endpoint: MRD 
Negativity has been updated to allow 
for a more precise estimate. 
Section 10.2.5 Reporting of SAEs to 
GSK 
The follow text has been 
removed: The investigator or 
medically-qualified sub-
investigator must show 
evidence within the eCRF (e.g., 
check review box, signature, 
etc.) of review and verification 
This requirement is no longer in effect.  
The need for Principal Investigators to 
document in the electronic case report 
form (eCRF) that they have reviewed 
the adverse event/serious adverse 
event and provide an assessment of 
causality is not required as they still 
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Original Section/Table/Figure 
Description of Change 
Brief Rationale 
of the relationship of each SAE 
to investigative product/study 
participation (causality) within 
72 hours of SAE entry into the 
eCRF. 
must document this assessment in the 
medical record as per the wording in 
Section 10.2.4. 
Section 10.18 Appendix 18 
COUNTRY SPECIFIC 
REQUIREMENTS (JAPAN) 
Appendix 18 has been added 
with country specific 
requirements for Japan.  
Country specific requirements for study 
conduct in Japan have been added to 
the global Protocol Amendment 03 
template. 
 
Amendment 02 JPN-1: 27-APR-2021 
Protocol Amendment 02 JPN-1 applies to all participants and all sites in Japan.  
Overall Rationale for the Amendment 02 JPN-1:  
The protocol has been amended to continue recruitment into a Japan expansion cohort 
after the enrollment into the global study is completed, to enable Japan-specific 
supplemental analyses to be performed, which will support the application for 
belantamab mafodotin to treat patients with relapsed/refractory multiple myeloma in 
Japan. 
The study conduct, including study objectives and endpoints, will remain the same for the 
Japan Expansion Cohort as for the global study. 
Original 
Section/Table/Figure 
Description of Change 
Brief Rationale 
Section 1.1 Synopsis 
Under the ‘Number of Participants’ heading, a Japan 
Expansion Cohort has been added so that once the 
enrollment into the global study is completed, recruitment 
into an expansion cohort will continue in Japan until a 
total of 
 Japanese participants have been enrolled. 
To continue recruitment into 
a Japan expansion cohort 
after the enrollment into the 
global study is completed, 
to enable Japan-specific 
supplemental analyses to 
be performed. 
Section 4.4 End of 
Study Definition 
An end of study definition has been added for the Japan 
Expansion Cohort. 
To clarify the end of study 
definition with regards to 
the global study and Japan 
Expansion Cohort. 
Section 9.2 Sample 
Size Determination 
Under the ‘Primary Endpoint: PFS’ heading, a Japan 
Expansion Cohort has been added with justification for 
the sample size of the Japanese participants in 
assessing the primary endpoint. 
To describe the Japan 
Expansion Cohort and 
justify the sample size of 
the Japanese participants. 
 
 
 
 
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Amendment 02: 16-DEC-2020 
Overall Rationale for the Amendment 02:  
The protocol has been amended to update exclusion criteria for HIV+, Hep B+, and 
Hep C+ participants in order to align with the latest regulatory (US FDA) guidance, to 
provide clarification to the administration of supportive infusion medications for 
daratumumab, and to clarify conditions regarding study intervention restart or 
rechallenge after liver stopping criteria are met.  
Additional changes were incorporated which align with program revisions and/or updates 
as listed in table below.   
Original Section/Table/Figure 
Description of Change 
Brief Rationale 
1.3 Schedule of Activities 
Clarified language on 
Screening period (both Arms) 
To clarify language 
Clarified language for collection 
of AEs and SAEs (Arm B) 
To clarify language 
Added clarifying language for 
analysis of biomarker and BM 
samples to be done if date and 
time have been recorded 
To clarify language  
Updated Table 2 (Arm B) 
footnote 5 vital signs based on 
edits in Section 8.2.3.2 
To clarify language 
Added Table 3 for BM Aspirate 
and Biopsy collection  
To clarify BM sample collection  
Added Table 4 for additional 
procedures for participants with 
a history of Hepatitis B  
To align with the latest regulatory 
guidance 
Added Table 5 for additional 
procedures for participants with 
a history of Hepatitis C 
To align with the latest regulatory 
guidance 
Removed triplicate ECG at 
Screening in case of QTcF 
prolongation (both Arms) 
To align with deletion of QTc stopping 
criteria (previous Section 7.1.3) as per 
belantamab mafodotin program-wide 
Cardiac Safety Panel 
recommendations 
3 Objectives and Endpoints 
Added the exploratory 
objective of assessment of 
imaging plus MRD negativity 
rate 
To maintain program-wide consistency 
4.3.2. Daratumumab Dose, 4.3.3. 
Bortezomib Dose, 4.3.4. 
Dexamethasone Dose, 6.1.2. 
Treatment Arm B Dosing Schedule, 
6.1.4.1. Daratumumab Required 
Pre/Post-medication, 6.5.2. Prohibited 
Concomitant Therapies, 6.6.2. 
Daratumumab, 7.1.4.2. Daratumumab 
Replaced references to 
USPI/SmPC of Darzalex and 
Velcade with reference to the 
most recently approved 
country-specific label 
To avoid discrepancies between 
USPI/SmPc and country-specific labels 
5.2 Exclusion Criteria 
Updated exclusion criteria for 
HIV+, Hep B+, and Hep C+ 
participants 
To align with the latest regulatory 
guidance 

 
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Original Section/Table/Figure 
Description of Change 
Brief Rationale 
6.1.1. Treatment Arm A Dosing 
Schedule - Dexamethasone" 
Added clarifying language for 
days of co-administration of 
treatments 
To correct a typographical error 

 
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Original Section/Table/Figure 
Description of Change 
Brief Rationale 
6.1.3 Belantamab Mafodotin and 
6.1.4 Daratumumab 
Added clarifying language for 
body weight at baseline and 
dose calculations in case of 
body weight changes 
To clarify dose calculations 
6.1.4.1 Daratumumab Required 
Pre/Post-medication 
Replaced existing language 
with reference to daratumumab 
label 
To clarify pre- and post-infusion 
medications for daratumumab 
administration based on the label 
guidance 
6.5.2 Prohibited Concomitant 
Medications 
Added language for 
participants receiving anti-HIV 
and anti-microbials: 
To align with the latest regulatory 
guidance 
6.6.4 Dexamethasone 
Clarified language for dose 
reduction if Dose Level -1 is 
not tolerated 
To clarify the dose modification for 
dexamethasone  
6.6.6 Management of Hepatitis B+ 
participants 
Added section to clarify 
management of Hepatitis B+ 
participants 
To align with the latest regulatory 
guidance 
7.1.2.1 Study Intervention Restart or 
Rechallenge after Liver Stopping 
Criteria Are Met 
Clarified that IRB/IEC approval 
is obtained if required 
To align with GSK liver monitoring 
requirements 
7.1.3 QTc Stopping Criteria 
Removed section 
To align with belantamab mafodotin 
program-wide Cardiac Safety Panel 
recommendations 
8.1 Efficacy Assessments and 8.1.3 
MRD Assessment and PET-CT 
Imaging 
Extended timepoint for MRD 
negativity confirmation by PET-
CT from 21 days to 42 Days 
To align with GSK program 
8.2.3.2 Vital Sign Measurement for 
Treatment Arm B 
Added clarifying language for 
measurements in case of 
daratumumab split dosing  
To clarify language 
8.9.1 Soluble BCMA Table 20 
Added clarifying language in 
table footnote for sBCMA 
sample collection in case 
daratumumab administration 
on C1D1 is split over Day 1 
and Day 2 
To clarify collection of sBCMA sample  
9.4.3 Pharmacokinetic Analyses 
Updated text by using a more 
precise language around the 
Population PK model 
To clarify the Population PK model to 
be used in the analysis 
10.4.1 Liver Safety Drug Restart or 
Re-Challenge Guidelines 
Clarified that IRB/IEC approval 
is obtained if required 
To align with GSK liver monitoring 
requirements 
10.9 Appendix 9: Corneal Event 
Grading and Prophylactic 
Interventions for Corneal Toxicity 
(Treatment Arm A) 
Clarified definition of corneal 
ulcer and definition of 
superficial keratopathy  
To align with GSK program 
10.16 Appendix 16 Data 
Management/Monitoring 
Added new Appendix on 
remote Data 
Management/Monitoring 
To allow flexibility in study conduct 
Throughout document 
Minor editorial and document 
formatting revisions 
Minor revisions without change to 
content, therefore have not been 
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Amendment 01: 16-JUL-2020 
Overall Rationale for the Amendment:  
The protocol has been amended based on regulatory agency comments. Additional 
changes were incorporated to align with program-wide revisions and/or updates. In 
addition, based upon feedback from regulatory agencies, a new Keratopathy Visual 
Acuity (KVA) scale has been introduced in this amendment for grading of treatment-
related corneal events. Furthermore, dose modification guidelines and stopping criteria 
for belantamab mafodotin for treatment-related corneal events have been aligned with the 
guidelines of the new KVA Scale. 
Protocol Amendment 1 includes the following: 
Original Section/Table/Figure 
Description of Change 
Brief Rationale 
1.1 Primary and Secondary 
Objectives and Endpoints 
Added the row for the Key 
Secondary Objective/Endpoint 
: Minimal Residual Disease 
(MRD) negativity rate. This was 
previously a secondary 
endpoint 
Differentiate the Key Secondary 
Objective/endpoint from other 
Secondary Objectives/endpoints based 
on regulatory agency feedback 
1.3 Schedule of Activities (SoA) Table 
1 and Table 2  
Added a new text related to 
Home Healthcare and 
Telemedicine Approaches 
To allow flexibility in study conduct 
1.3 Schedule of Activities (SoA) – Arm 
A and ARM B 
Bone Marrow sample for 
BCMA expression; added 
required biopsy in addition to 
aspirate collection for 
biomarker research. Replaced 
aspirate clot by aspirate. 
 
Change in sample type due to observed 
assay failure secondary to hemodilution 
in bone marrow aspirate clots. BCMA 
IHC is validated in bone marrow biopsy 
samples  
1.3 Schedule of Activities (SoA) – Arm 
A and ARM B  
• Ocular Exam: updated 
language and footnote 
number 
• Adverse Events/SAEs: 
updated the language 
• Added Urine dipstick for 
protein 
• Imaging for Extramedullary 
Disease: updated schedule 
requirement 
• Bone Marrow Assessments: 
updated language for 
optional samples 
• Updated footnotes 11,13, 
15, 21 and 22 
Ocular exam language updated based 
on regulatory agency feedback for Arm 
A. Ocular exam updated for Arm B per 
program-wide language. 
Administrative changes were made as 
described. 
1.3. SoA (Arm B). 
Added requirement to undergo 
central testing with a 
daratumumab-specific 
immunofixation assay to 
confirm PD or CR/sCR 
To be consistent with the assessment 
of CR where daratumumab Interference 
is suspected (Section 8.1.2) 

 
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Original Section/Table/Figure 
Description of Change 
Brief Rationale 
2.1 Study Rationale 
Update text regarding the 
mechanism of action of 
belantamab mafodotin 
To clarify the mechanism of action of 
belantamab mafodotin 
2.2.3 Figure 1 
The figure of Mechanism of 
Action has been updated  
To clarify the mechanism of action of 
belantamab mafodotin 
2.3.1 Summary of Risk Assessment 
for Belantamab Mafodotin (Treatment 
Arm A), Daratumumab (Treatment 
Arm B), and Bor/Dex (Treatment 
Arms A and B) 
Inserted Seizures and 
Progressive multifocal 
leukoencephalopathy (PML) 
description 
Updated to comply with bortezomib 
label 
2.2.4 Clinical Experience with 
Belantamab Mafodotin 
Added Section: 
2.2.4.1. Safety and Section 
2.2.4.2. Pharmacokinetics and 
Pharmacodynamics in 
Humans. 
 
Updated the existing text 
regarding safety and efficacy. 
To reflect latest clinical and safety 
information included in the new IB 
Version 8. 
2.2.4.2 Clinical Pharmacokinetics  
Updated the section number 
and title to 2.2.4.2. 
“Pharmacokinetics and 
Pharmacodynamics in 
Humans” 
 
Updated text regarding the 
pharmacokinetics and 
pharmacodynamics of 
belantamab mafodotin 
To reflect latest clinical and safety 
information included in the new IB 
Version 8. 
3 Objective and Endpoints 
Added the row for the Key 
Secondary Objective : Minimal 
Residual Disease (MRD) 
negativity rate. This was 
previously included as a 
secondary objective 
 
Deleted the exploratory 
objective of assessment of 
imaging plus MRD negativity 
rate 
Differentiate the Key Secondary 
Objective from other Secondary 
Objectives 
 
 
 
 
To maintain program-wide consistency 
5.1 Inclusion Criteria 
Updated the IC 4 as: 
“Previously treated with at least 
1 prior line of MM therapy, and 
must have documented 
disease progression during or 
after their most recent therapy.  
 
Note: induction + ASCT + 
maintenance is 1 line of 
therapy” 
 
 
 
Updated language IC #10  
IC4 updated in acknowledgement of the 
fact that progressive disease during or 
after most recent therapy prior to 
enrolment might not be fully according 
to IMWG criteria. Routine clinical 
practice may not collect sufficient 
information about disease status to 
confirm disease progression treatment 
lines prior to study entry using formal 
IMWG criteria. Clinical assessment of 
disease progression by the investigator 
will be utilized. 
On-study disease response will still be 
assessed according to IMWG criteria. 
 
 

 
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Original Section/Table/Figure 
Description of Change 
Brief Rationale 
Added the time for the use of 
contraceptives post-last dose for 
patients having received daratumumab. 
Updated time of contraceptive use 
related to belantamab mafodotin. 
5.1 Inclusion Criteria Table 3 - 
Adequate Organ System Function 
Based on Safety Assessments 
Added Urine dipstick for protein 
test 
Updated language  
To add an optional method to screen 
for urine protein 
5.3 Lifestyle Considerations 
 
Clarified language regarding 
the use of contact lenses. 
 
Moved the sentence about 
administration of live/ live-
attenuated vaccine to 
Prohibited Concomitant 
Medication.  
 
 
 
The text was moved to a more 
appropriate section 
6.1.1 Treatment Arm A Dosing 
Schedule 
Added new text related to 
Home Healthcare and 
Telemedicine Approaches 
To allow flexibility in study conduct 
6.1.2 Treatment Arm B Dosing 
Schedule 
Added new text related to 
Home Healthcare and 
Telemedicine Approaches 
To allow flexibility in study conduct 
6.1.2. Daratumumab 
Specified the number of weeks 
corresponding to the cycle 
number during the treatment 
with daratumumab 
To clarify the dosing schedules 
6.1.6 Dexamethasone 
Updated language 
To clarify dose modification 
6.5.2 Prohibited Concomitant 
Therapies 
Added administration of live/ 
live-attenuated vaccine text. 
See the change for Section 5.3 
above. 
To enhance patients’ safety, the period 
for prohibited use of live/live-attenuated 
vaccines has been extended 
6.6.1 Belantamab Mafodotin – Table 
6 Dose Modifications 
Urine dipstick for protein test 
has been added. (New Table 
7) 
Urine dipstick added as an optional 
method to screen for urine protein 
 
6.6.1 Belantamab mafodotin Dose 
Modification 
Added a new table- Table 9- 
General Dose Modification and 
Management Guidelines for 
Drug-Related Adverse Events 
Not Otherwise Specified 
To further clarify dose modification for 
adverse events associated with 
belantamab mafodotin 
6.6.1. Belantamab mafodotin dose 
modification for Corneal AEs 
A table that provided guidelines 
for treatment-related corneal 
events that was originally in 
Appendix 9 was moved to 
Section 6.6.1 in the 
amendment. This table in 
Section 6.6.1 has been 
replaced by a new table (Table 
8) that provides updated 
guidelines for treatment-related 
corneal events based on 
Keratopathy Visual Acuity 
Scale for grading corneal 
events that is now in Appendix 
9 as a new table (Table 26).  
 
To move key dose modification into a 
more appropriate section and improve 
clarity of qualifications of eye care 
specialists. The dose modification 
guidelines for belantamab mafodotin 
treatment-related corneal events have 
been updated for additional clarity and 
these are based on a new Keratopathy 
Visual Acuity Scale for treatment-
related corneal events (in Appendix 9) 
that takes in consideration both corneal 
examination findings as well as visual 
acuity changes to grade the corneal 
toxicities. 

 
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Original Section/Table/Figure 
Description of Change 
Brief Rationale 
The new Appendix 10 lists the 
required qualifications of eye 
care specialists who will 
assess corneal AEs. 
6.6.4 Dexamethasone 
Added a new table – Table 12-
to provide guidelines for 
permitted dose reductions for 
Dexamethasone in both 
treatment Arms 
To clarify dose modification for 
dexamethasone 
7.1.2. Liver Chemistry Stopping 
Criteria 
 
Updates to GSK liver safety 
algorithm 
To align with GSK liver monitoring 
requirements.  
7.1.2.1 Study Intervention Restart or 
Rechallenge after Liver Stopping 
Criteria Are Met 
Updates to GSK liver safety 
algorithm 
To align with GSK liver monitoring 
requirements.  
8 Study Assessment and Procedures 
Added new text related to 
Home Healthcare and 
Telemedicine Approaches 
To allow flexibility in study conduct 
8 Study Assessment and Procedure – 
Table 11 
• Urine dipstick for protein 
has been added - (Now 
Table 15) 
 
• Bone Marrow Aspiration / 
Biopsy section has been 
updated  
To allow sites to use urine dipstick 
testing as a first pass for urine protein 
monitoring at screening.  
 
To clarify the distinction between 
mandatory and optional BM tests for 
biomarker analysis 
8.2.6.1 Treatment Arm A 
Updated ocular assessment 
schedule 
To clarify ocular assessment for 
participants treated with belantamab 
mafodotin based on regulatory agency 
feedback. 
8.2.6.2 Treatment Arm B 
Updated ocular assessment 
schedule 
To clarify ocular assessment for 
participants treated with daratumumab.  
8.2.8 Pregnancy Testing (WOCBP 
only) 
Language has been updated to 
add the duration of required 
contraception for patients 
receiving daratumumab. 
 
Updated time of contraceptive 
use related to belantamab 
mafodotin  
Ensure clarity of requirements  
 
 
 
 
To reflect latest clinical and safety 
information included in the new IB 
Version 8 
8.3.5 Pregnancy  
Updated time of contraceptive 
use related to belantamab 
mafodotin  
To reflect latest clinical and safety 
information included in the new IB 
Version 8 

 
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Original Section/Table/Figure 
Description of Change 
Brief Rationale 
8.4 Overdose 
Dose holding guidance 
updated in setting of overdose. 
 
Monitor closely for AEs/SAEs 
and laboratory abnormalities 
until: 
(a) belantamab mafodotin can 
no longer be detected 
systemically (at least 3 
months);  
(b) Monitor closely for AEs, 
SAEs, and laboratory 
abnormalities until resolution. 
 
Provided guidance re. timing of 
obtaining an additional PK and 
serum sBCMA sample in the 
event of an overdose. 
 
New PK data supports revised 
guidance. 
 
8.9.2 Tumor related biomarkers 
Language updated 
Clarified which sampling for biomarker 
analysis is optional. 
9.2 Sample Size Determination 
Added description of sample 
size justification for MRD 
negativity 
Description of sample size and power is 
provided since MRD Negativity is a key 
secondary endpoint that will be formally 
tested 
9.4.1 Table 17 
Stats analysis methods table 
updated to include the new key 
secondary endpoint of MRD 
Negativity (Now Table 21) 
Added details of how MRD will be 
analysed and described in the study 
report. 
9.1.1. Multiplicity  
New subsection added to 
address multiplicity of analysis 
issues. 
Description of sample size and power is 
provided since MRD Negativity is a key 
secondary endpoint that will be formally 
tested 
9.5  
Table 19 Summary of Planned 
Interim Analyses 
Table 20 Stopping Boundaries for 
Interim Analyses 
• (Now Table 23 and Table 
24) 
• Updates were made to the 
planned interim analysis 
and stopping boundaries 
due to changing the 
information fraction for the 
second PFS analysis to a 
higher fraction to provide 
more mature efficacy data. 
 
• Due to the inclusion of the 
new key secondary 
endpoint of MRD Negativity 
in the testing hierarchy 
procedure at the second 
PFS interim analysis, 
stopping boundaries were 
added 
Following the regulatory agency 
comments, the second PFS interim 
analysis that was to be performed at 
% information has been changed to 
occur at
% information fraction. 
 
 
 
 
 
 
A summary description of the stopping 
rules for MRD negativity at the second 
PFS interim analysis is needed for the 
protocol    
CCI
CCI

 
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Original Section/Table/Figure 
Description of Change 
Brief Rationale 
10.4 Liver safety (Appendix 4) 
• INR follow-up analysis now 
applies to ALL countries 
and not just Japan. 
• Blood sample for PK 
analysis and for sBCMA 
now to be obtained within 
70 days, and not 45 days, 
after last dose of 
belantamab mafodotin.  
• Updates made to the GSK 
liver safety algorithm 
Revised per GSK standard for liver 
safety 
 
 
Follow-up lengthened based on new pk 
data 
 
 
Revised per GSK standard for liver 
safety 
10.9 Appendix 9: Corneal Event 
Grading and Prophylactic 
Interventions for Corneal Toxicity 
(Treatment Arm A) 
 
Appendix title modified to 
“Corneal Event Grading and 
Prophylactic Interventions for 
Corneal Toxicity (Treatment 
Arm A)”. A new Keratopathy 
Visual Acuity (KVA) Scale for 
treatment-related corneal 
events (new Table 26) has 
been added that provides 
guidance for grading treatment-
related corneal events.  
This updated grading scale (KVA scale) 
for treatment-related corneal events 
takes in consideration both corneal 
examination findings as well as visual 
acuity changes to grade the corneal 
toxicities. 
10.10 Eye care specialist’s 
qualifications and requirements 
Added a new Appendix 10: Eye 
care specialist’s qualifications 
and requirements 
To clarify the qualifications and 
expectations for eye care specialist 
responsible for eye exams 
10.12 Country specific requirements 
GFR formula included for 
Japan 
To be consistent with GSK standard 
10.16 Home Healthcare and 
Telemedicine Approaches 
Added a new Appendix to allow 
Home Healthcare and 
Telemedicine Approaches 
To allow flexibility in study conduct 
 

 
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10.18. 
Appendix 18 COUNTRY SPECIFIC REQUIREMENTS (JAPAN) 
Effective Date:  
 23 Oct 2024 
Version: 
Amendment 7 JPN-1 
 
10.18.1. 
Study Conduct Considerations 
10.18.1.1. Regulatory and Ethical Considerations 
The study will be conducted in accordance with “the Ministerial Ordinance on the 
Standards for the Conduct of Clinical Trials of Medicinal Products (MHW Notification 
No.28 dated 27th March, 1997)” and Pharmaceuticals and Medical Devices Act. 
The statement “I acknowledge that I am responsible for overall the study conduct.” on the 
Investigator Protocol Agreement Page means the investigator’s responsibility defined by 
Japanese GCP. 
GSK will submit the CTN to the regulatory authorities in accordance with 
Pharmaceuticals and Medical Devices Act before conclusion of any contract for the 
conduct of the study with study sites. 
10.18.1.2. Informed Consent 
Prior to participation in the study, the investigator should fully inform the potential 
participant and/or the participant's legally acceptable representative of the study including 
the written information. The investigator should provide the participant and/or the 
participant's legally acceptable representative ample time and opportunity to inquire 
about details of the study. The participant and/or the participant’s legally acceptable 
representative should sign and personally date the consent form. The participant may 
consider the content of the written information at home. The person, who conducted the 
informed consent discussion and the study collaborator giving supplementary 
explanation, where applicable, should sign and personally date the consent form. If an 
impartial witness is required, the witness should sign and personally date the consent 
form. The investigator should retain this signed and dated form (and other written 
information) together with the source medical records, such as clinical charts (in 
accordance with the rules for records retention, if any, at each medical institution) and 
give a copy to the participant and/or the participant’s legally acceptable representative. If 
the participant is a minor, document informed consent will be obtained from both the 
participant and his/her legally acceptable representative. In addition, if a minor 
participant reaches an adult during the treatment period, the participant's consent to 
participate in the clinical trial will be obtained again. 
10.18.1.3. Study Period 
MAY 2021 – AUG 2026 

 
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10.18.1.4. Study Administrative Structure 
Sponsor information is included in Exhibit 1. List of Medical Institutions and 
Investigators is included in Exhibit 2. 
10.18.2. 
Unapproved Medical Device 
GSK will provide patients a medical device which is not approved in Japan but this has 
been approved for use on this study in other countries.. 
Unapproved medical device AE/SAE or deficiencies, including those resulting from 
malfunctions of the device, must be detected, documented, and reported by the 
investigator throughout the study. 
Unapproved Medical Device 
General Name 
Manufacturer Name 
Brand Name 
Cooling Pack 
ANDWIN SCIENTIFIC 
EYE MASK, COLD GEL  
Cooling Pack 
Flents 
Hot/Cold Eye Mask 
 
NOTE: Deficiencies fulfilling the definition of an AE/SAE will also follow the processes 
outlined in Section 10.2 of the protocol. 
 
10.18.2.1. Definitions of an Unapproved Medical Device Adverse Events (AEs), 
Adverse Device Effects (ADEs), Serious Adverse Events (SAEs), 
Serious Adverse Device Effect (SADE), Unanticipated Serious Adverse 
Device Effect (USADE) and Device Deficiencies 
• 
The definitions and procedures detailed in this appendix are in accordance with ISO 
14155 and European Union Medical Device Regulation (MDR) 2017/745 for clinical 
trials of medical devices (if applicable).  
• 
Both the investigator and the sponsor will comply with all local medical device 
reporting requirements. 
• 
The detection and documentation procedures of AE/SAE or deficiencies described in 
this protocol apply to all unapproved medical devices provided for use in the study. 
 
Definition of Unapproved Medical Device AE and Unapproved Medical Device ADE 
Unapproved Medical Device AE and Unapproved Medical Device ADE Definition  
• An unapproved medical device AE is any untoward medical occurrence, in a 
clinical study participants, users, or other persons, whether or not considered 
related to the investigational medical device. An unapproved medical device AE 
can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally 

 
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associated with the use of an investigational medical device. This definition 
includes events related to the unapproved medical device or comparator and events 
related to the procedures involved. 
• An unapproved medical device adverse device effect (ADE) is defined as an 
adverse event related to the use of an unapproved medical device. This definition 
includes any adverse events resulting from insufficient or inadequate instructions 
for use, deployment, implantation, installation, or operation, or any malfunction of 
the unapproved medical device as well as any event resulting from use error or 
from intentional misuse of the unapproved medical device. 
 
Definition of Unapproved Medical Device SAE, SADE and USADE 
An unapproved medical device SAE is an unapproved AE that: 
a. Led to death  
b. Led to serious deterioration in the health of the participant, that either resulted in: 
1. A life-threatening illness or injury. 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 were more severe 
2. A permanent impairment of a body structure or a body function, 
3. Inpatient or prolonged hospitalization, Planned hospitalization for a pre-
existing condition, or a procedure required by the protocol, without serious 
deterioration in health, is not considered an SAE 
4. Medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to a body structure or a body function 
c. Led to fetal distress, fetal death or a congenital abnormality or birth defect 
d. Is a suspected transmission of infectious agents via unapproved medical devices 
Unapproved medical device SADE definition 
• A SADE is defined as an adverse device effect that has resulted in any of the 
consequences characteristic of a serious adverse event. 
• All unapproved medical device deficiencies leading to a serious adverse event due 
to lack of appropriate action, lack of intervention, or disadvantage of the 
environment are included. Any unapproved medical device deficiency that might 
have led to an SAE if appropriate action had not been taken, intervention had not 
occurred, or circumstances had been less fortunate. 
Unapproved medical device USADE definition 
• A USADE is a serious adverse device effect which by its nature, incidence, severity 
or outcome has not been identified in the current version of the instructions for use. 

 
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Definition of Unapproved Medical Device Deficiency 
Unapproved Medical Device Deficiency definition 
• An unapproved medical device deficiency is an inadequacy of a medical device 
with respect to its identity, quality, durability, reliability, safety, or performance. 
Unapproved medical device deficiencies include malfunctions, use errors, and 
information supplied by the manufacturer. 
 
10.18.2.2. Time Period for Detecting Unapproved Medical Device Deficiencies 
• 
Unapproved medical device deficiencies that result in an incident will be detected, 
documented, and reported during all periods of the study in which the medical device 
is used.  
• 
If the investigator learns of any deficiency at any time after a participant has been 
discharged from the study, and such deficiency is considered reasonably related to an 
unapproved medical device provided for the study, the investigator will promptly 
notify the sponsor. 
 
10.18.2.3. Follow-up of Unapproved Medical Device Deficiencies 
• 
Follow-up of unapproved medical device deficiency applies to all participants, 
including those who discontinue study treatment. 
• 
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the deficiency. 
• 
New or updated information will be recorded on the originally completed form with 
all changes signed and dated by the investigator. 
 
10.18.2.4. Recording and Follow-Up of Unapproved AE and/or SAE and Device 
Deficiencies 
Unapproved Medical Device AE and/or SAE and Device Deficiency Recording 
• When an unapproved medical device AE and/or /SAE/device deficiency occurs, it 
is the responsibility of the investigator to review all documentation (e.g., hospital 
progress notes, laboratory reports, and diagnostics reports) related to the event. 
• The investigator will then record all relevant unapproved medical device 
AE/SAE/device deficiency information in the participant’s medical records, in 
accordance with the investigator’s normal clinical practice, and on the appropriate 
form. 

 
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Unapproved Medical Device AE and/or SAE and Device Deficiency Recording 
• It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to the sponsor in lieu of completion of the unapproved medical 
device AE and/or SAE/device deficiency form. 
• There may be instances when copies of medical records for certain cases are 
requested by the sponsor. In this case, all participant identifiers, with the exception 
of the participant number, will be redacted on the copies of the medical records 
before submission to the sponsor. 
• The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not 
the individual signs/symptoms) will be documented as the unapproved medical 
device AE and/or SAE. 
• For device deficiencies, it is very important that the investigator describes any 
corrective or remedial actions taken to prevent recurrence of the deficiency. 
Assessment of Intensity 
• The investigator will make an assessment of intensity for each unapproved medical 
device AE/SAE reported during the study and assign it to one of the following 
categories:  
• Mild: An event that is easily tolerated by the participant, causing minimal 
discomfort and not interfering with everyday activities. 
• Moderate: An event that causes sufficient discomfort and interferes with normal 
everyday activities. 
• Severe: An event that prevents normal everyday activities. An AE that is assessed 
as severe should not be confused with a SAE. Severe is a category utilized for 
rating the intensity of an event; and both AEs and SAEs can be assessed as severe. 
• An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes 
as described in the definition of an unapproved medical device SAE, NOT when it 
is rated as severe. 
• Other measures to evaluate AEs and SAEs may be utilized (e.g., National Cancer 
Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]). 
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE/device deficiency 
• 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• 
The investigator will use clinical judgment to determine the relationship. 

 
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Assessment of Causality 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• 
The investigator will also consult the instructions for use, in his/her assessment. 
• 
For each AE/SAE/device deficiency, the investigator must document in the 
medical notes that he/she has reviewed the unapproved medical device 
AE/SAE/device deficiency and has provided an assessment of causality. 
• 
There may be situations in which an unapproved medical device SAE has occurred 
and the investigator has minimal information to include in the initial report to 
GSK. However, it is very important that the investigator always make an 
assessment of causality for every event before the initial transmission of the SAE 
data to GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an unapproved medical device SAE follow-up report with 
the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of unapproved medical device AE and/or SAE, and device deficiency 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK 
to elucidate the nature and/or causality of the unapproved AE and/or SAE, and 
device deficiency as fully as possible. This may include additional laboratory tests 
or investigations, histopathological examinations, or consultation with other health 
care professionals. 
• 
If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide GSK with a copy of any 
post-mortem findings including histopathology.  
• 
New or updated information will be recorded in the originally completed form. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 

 
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10.18.2.5. Reporting of Unapproved Medical Device SAEs 
Unapproved Medical Device SAE Reporting to GSK via an Electronic Data 
Collection Tool 
• 
The primary mechanism for reporting an unapproved medical device SAE to GSK 
will be the electronic data collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper unapproved 
medical device SAE data collection tool (see next section) in order to report the 
event within 24 hours. 
• 
The site will enter the unapproved medical device SAE data into the electronic 
system as soon as it becomes available. 
• 
After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new unapproved medical device SAE from a study 
participant or receives updated data on a previously reported SAE after the 
electronic data collection tool has been taken off-line, then the site can report this 
information on a paper unapproved medical device SAE form (see next section) or 
to the [GSK medical monitor/SAE coordinator] by telephone. 
• 
Contacts for SAE reporting can be found in Appendix 2. 
 
Unapproved Medical Device SAE Reporting to GSK via Paper Data Collection 
Tool 
• 
Facsimile or e-mail transmission of the unapproved medical device SAE paper  
data collection tool is the preferred method to transmit this information to the GSK 
medical monitor or the SAE coordinator. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the unapproved medical device SAE paper 
data collection tool sent by overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the unapproved medical device SAE  paper data collection tool 
within the designated reporting time frames. 
• 
Contacts for unapproved medical device SAE reporting can be found in Appendix 
2 
 
10.18.2.6. Reporting of SADEs 
SADE Reporting to GSK  
NOTE: There are additional reporting obligations for medical device deficiency that 
are potentially related to SAEs that must fulfil the legal responsibility to notify 

 
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SADE Reporting to GSK  
appropriate regulatory authorities and other entities about certain safety 
information relating to medical devices being used in clinical studies.  
• 
Any device deficiency that is associated with an SAE must be reported to GSK 
within 24 hours after the investigator determines that the event meets the 
definition of an unapproved device deficiency. 
• 
GSK shall review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These medical device deficiencies are 
reported to the regulatory authorities and IRBs/IECs as required by national 
regulations. 
• 
Contacts for SAE reporting can be found in Appendix 2. 
 
10.18.2.7. Prompt Reporting of Unapproved Medical Device Deficiencies to 
Sponsor 
• 
Unapproved Medical device deficiencies will be reported to the sponsor within 24 
hours after the investigator determines that the event meets the above Section 
10.18.2.1. Definitions of an Unapproved Medical Device Deficiency. 
• 
The Medical Device Deficiency Report Form will be sent to the sponsor by e-mail. If 
e-mail is unavailable, then postal or home delivery services should be utilized. 
• 
The same individual will be the contact for the receipt of unapproved medical device 
reports and SAE. 
 
10.18.2.8. Regulatory Reporting Requirements for Unapproved Medical Device 
Deficiencies 
• 
The investigator will promptly report all deficiencies occurring with any unapproved 
medical device provided for use in the study in order for the sponsor to fulfill the 
legal responsibility to notify appropriate regulatory authorities and other entities 
about certain safety information relating to unapproved medical devices being used 
in clinical studies. 
The investigator, or responsible person according to local requirements (eg, the head of 
the medical institution), will comply with the applicable local regulatory requirements 
relating to the reporting of deficiencies to the IRB/IEC.

 
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10.18.3. 
Modification to the full protocol 
10.18.3.1. Study procedure and exclusion criterion for hepatitis B (Protocol Section 1.3 and Section 5.2) 
Study procedure and exclusion criterion for hepatitis B are modified in accordance with guidelines for the management of hepatitis B 
virus infection by the Japanese Society of Hepatology.  
Table Hepatitis B (HBV) SoA – Additional Procedures (Section 1.3 Table 4) 
Note: The procedures listed in this table apply ONLY to participants in screening and who have been enrolled and who have a history of Hepatitis B; all procedures must be done 
as needed in addition to the required procedures for all participants detailed in Table 1 and Table 2 
HBV Study Assessments 
During Screening / 
Prior to starting 
treatment 
During 
Treatment 
EOT 
Notes 
HBV related Liver Imaging3 
X1 
X1 
X1 
1. Liver imaging (specific test per standard of care at local institution) in HBsAg+ 
participants to rule-out/identify cirrhosis, focal hepatic lesions, and/or biliary 
abnormalities at baseline. Repeat imaging at one year after starting treatment 
if still on treatment and twice yearly thereafter as long as participant remains 
on study treatment or as clinically indicated. 
2. HBV-DNA testing prior to the start of study treatment and subsequently every 
3 months, or if LFT elevations requiring increased monitoring or stopping 
criteria occur, or for any clinical suspicion of hepatitis reactivation. 
3. HBsAg+ participants only. 
4. For HBsAg+ participants, appropriate antiviral treatment per local guidance 
(e.g. tenofovir or entecavir) is started before starting study treatment, 
continues through to completion of treatment and should not be stopped 
unless advised by local hepatology or virology services. 
HBV-DNA testing 
X2 
X2 
X2 
HBeAg and HBeAb testing 
X3 
 
 
Prevention of HBV 
reactivation 
X4 
X4 
X4 
 
HBeAb = Hepatitis e antibody; HBeAg = Hepatitis e antigen; HBsAg = Hepatitis B surface antigen; HBV = Hepatitis B; LFT = liver function test 
 

 
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Exclusion criteria (Section 5.2) 
20. Patients with Hepatitis B will be excluded unless the following criteria can be met. 
Serology 
Screening 
During Study Treatment 
HBcAb+ and/or 
HBsAb+ 
AND 
HbsAg- 
• 
HBV DNA undetectable 
• 
Monitoring per protocol (Table 
18) 
• 
Antiviral treatment instituted if 
HBV DNA becomes detectable 
HBsAg+ at screen or 
within 3 months prior 
to first dose  
• 
After assessing HBeAg, HBeAb and HBV 
DNA, HBV DNA must be undetectable. 
Enrolment should be agreed with a 
hepatologist 
• 
Highly effective antiviral treatment started at 
least 4 weeks prior to first dose of study 
treatment 
• 
Baseline imaging per protocol 
• 
Participants with cirrhosis are excluded 
• 
Antiviral treatment maintained 
throughout study treatment 
• 
Monitoring and management 
per protocol (Table 18) 
NOTE: presence of Hep B surface antibody (HBsAb) indicating previous vaccination will not exclude a 
participant. 
 
10.18.3.2. Genetics (Protocol Section 8.8 and Appendix 5) 
In this study, genetics may be evaluated after review by the ethical review committee 
established by GSK in accordance with Japanese ethical guidelines for human 
genome/gene analysis research (see Section 8.8 Genetics of the protocol).  

 
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10.18.3.3. CONTRACEPTIVES ALLOWED DURING THE STUDY (Appendix 3) 
Of contraceptive methods defined in the protocol Appendix 3, Contraceptive Methods 
Approved in this Study, the followings are not approved in Japan as contraceptive 
method. 
Highly Effective Methods That Have Low User Dependency 
• 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation 
Highly Effective Methods That Are User Dependent 
• 
Combined (estrogen- and progestogen-containing ) hormonal contraception 
associated with inhibition of ovulation  
• 
intravaginal 
• 
transdermal 
• 
injectable 
• 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
• 
oral 
• 
injectable 
Acceptable Methods 
• 
Progestogen-only oral hormonal contraception where inhibition of ovulation is not 
the primary mode of action 
• 
female condom 
• 
cervical cup 
• 
diaphragm 
• 
sponge with spermicide 
 

 
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208 
11. 
REFERENCES 
Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research 
and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international 
clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-376. 
Andrade RJ, Robles M, Lucena MI. Rechallenge in drug-induced liver injury: the 
attractive hazard. Expert Opin Drug Saf. 2009;8:709-714. 
Babb J, Rogatko A, Zacks S. Cancer phase I clinical trials: efficient dose escalation with 
overdose control. Stat Med. 1998 May 30;17(10):1103-1120. 
Basch E, Reeve BB, Mitchell SA, et al. Development of the National Cancer Institute's 
patient-reported outcomes version of the common terminology criteria for adverse events 
(PRO-CTCAE). J Natl Cancer Inst. 2014;106(9). 
Bellucci, R, Alyea, EP, Chiaretti, S, et al. Graft-versus-tumor response in patients with 
multiple myeloma is associated with antibody response to BCMA, a plasma-cell 
membrane receptor. Blood. 2005;105(10):3945-3950. 
Belnoue, E, Pihlgren, M, McGaha, TL, et al. APRIL is critical for plasmablast survival in 
the bone marrow and poorly expressed by early-life bone marrow stromal cells. Blood. 
2008;111(5):2755-2764. 
Bretz F, Maurer W, Brannath W, et al. A graphical approach to sequentially rejective 
multiple test procedures. Statistics in medicine. 2009;28(4):586-604. 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. 
Biometrics. 1982;38(1):29-41. 
Cartier S, Zhang B, Rosen VM, et al. Relationship between treatment effects on 
progression-free survival and overall survival in multiple myeloma: a systematic review 
and meta-analysis of published clinical trial data. Oncol Res Treat. 2015;38(3):88-94. 
Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E, Bonomi A,et al. The Functional 
Assessment of Cancer Therapy scale: development and validation of the general measure. 
Journal of Clinical Oncology, 1993;11(3): 570-579. 
Cocks K, Cohen D, Wisløff F, et al. An international field study of the reliability and 
validity of a disease-specific questionnaire module (the QLQ-MY20) in assessing the 
quality of life of patients with multiple myeloma. Eur J Cancer. 2007 Jul;43(11):1670-
1678. 
Cowan AJ, Allen C, Barac A, et al. Global burden of multiple myeloma: a systematic 
analysis for the global burden of disease study 2016. JAMA Oncol. 2018 Sep 
1;4(9):1221-1227. 
Darce JR, Arendt BK, Wu X, et al. Regulated expression of BAFF-binding receptors 
during human B cell differentiation. J Immunol. 2007;179(11):7276-7286. 

 
CONFIDENTIAL 
 
 
207503 
 
Protocol Amendment 7 JPN-1 
23 Oct 2024 
209 
Darzalex SmPC (2019). https://www.ema.europa.eu/en/documents/product-
information/darzalex-epar-product-information_en.pdf (Last visited: 4 Dec 2019). 
Darzalex USPI (2019). 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761036s024lbl.pdf (Last 
visited: 4 Dec 2019). 
Dexamethasone SmPC. 2018. 
https://www.medicines.org.uk/emc/product/5411/smpc/print. 
Dexamethasone USPI. 2018. 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/40572s002lbledt.pdf. 
Dimopoulos M, Sonneveld P, Nahi H, et al. Progression-free survival as a surrogate 
endpoint for overall survival in patients with relapsed or refractory multiple myeloma. 
Value Health. 2017;20(9): A408. 
Dimopoulos MA, Orlowski RZ, Facon T, et al. Retrospective matched-pairs analysis of 
bortezomib plus dexamethasone versus bortezomib monotherapy in relapsed multiple 
myeloma. Hematologica. 2015;100:100-106. 
Dougherty BE, Nichols JJ, Nichols KK. Rasch analysis of the Ocular Surface Disease 
Index (OSDI). Invest Ophthalmol Vis Sci. 2011 ;52(12): 8630-8635. 
GSK2857916 Investigator’s Brochure, v12. GSK document No. RPS-CLIN-105644. 
Effective 23 May 2024. 
Guy W (ed). ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: US 
Department of Health, Education, and Welfare Public Health Service Alcohol, Drug 
Abuse, and Mental Health Administration, 1976. 
Hou H-A, Tang C-H, Liu H-Y, Qiu H. Real world treatment patterns and survival in 
patients with multiple myeloma in Taiwan. Blood. 2017;130:5434.  
Huang B, Tian L. Utilizing restricted mean duration of response for efficacy evaluation 
of cancer treatments. Pharm Stat. 2022 Sep;21(5):865-878. doi: 10.1002/pst.2198. Epub 
2022 Feb 21. PMID: 35191170. 
Hunt CM. Mitochondrial and immunoallergic injury increase risk of positive drug 
rechallenge after drug-induced liver injury: A systematic review. Hepatol. 2010;52:2216-
2222. 
Jiang C, Loo WM, Greenley EJ, et al. B cell maturation antigen deficiency exacerbates 
lymphoproliferation and autoimmunity in murine lupus. J Immunol. 2011 ;186(11): 6136-
6147. 
Kropff MH, Bisping G, Wenning D, Berdel WE, Kienast J. Bortezomib in combination 
with dexamethasone for relapsed multiple myeloma. Leuk Res. 2005 May;29(5):587-90. 

 
CONFIDENTIAL 
 
 
207503 
 
Protocol Amendment 7 JPN-1 
23 Oct 2024 
210 
Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group 
consensus criteria for response and minimal residual disease assessment in multiple 
myeloma. Lancet Oncol. 2016;17(8):e328-346. 
Kumar SK, Dispenzieri A, Lacy MQ, et al. Continued improvement in survival in 
multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 
2014;28(5):1122-1128. 
Kumar SK, Lee, JH, Lahuerta, JJ, et al. Risk of progression and survival in multiple 
myeloma relapsing after therapy with IMiDs and bortezomib: a multicenter international 
myeloma working group study. Leukemia. 2012;26(1):149-157. 
Kumar SK, Rajkumar SV, Dispenzieri A, et al. Improved survival in multiple myeloma 
and the impact of novel therapies. Blood. 2008;111(5):2516-2520. 
Kyprolis SmPC. (2018). https://www.ema.europa.eu/documents/product-
information/kyprolis-epar-product-information_en.pdf (Last visited: 16 Nov 2018). 
Kyprolis USPI. (2019). https://www.pi.amgen.com/~/media/amgen/repositorysites/pi-
amgen-com/kyprolis/kyprolis_pi.pdf (Last visited: 15 May 2019). 
Lan KKG, DeMets DL. Discrete sequential boundaries for clinical trials. Biometrika. 
1983;70:659-663. 
Laurent SA, Hoffmann FS, Kuhn PH, et al. Gamma-secretase directly sheds the survival 
receptor BCMA from plasma cells. Nat Commun. 2015 ;6 :7333.  
Li X, Wulfsohn MS, Koch GG. Considerations on testing secondary endpoints in group 
sequential design. Statistics in Biopharmaceutical Research. 2017 Oct 2;9(4):333-7. 
Lonial S, Anderson KC. Association of response endpoints with survival outcomes in 
multiple myeloma. Leukemia. 2014;28(2):258-268. 
Lonial S, Weiss BM, Usmani SZ, et al. Daratumumab monotherapy in patients with 
treatment-refractory multiple myeloma (SIRIUS): an open-label, randomized, phase 2 
trial. Lancet. 2016 Apr 9;387(10027):1551-1560. 
Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory 
multiple myeloma (DREAMM-2): a two-arm, randomized, open-label, phase 2 study. 
Lancet Oncol. 2020:21:207-21. 
Montes De Oca R, Bhattacharya S, Vitali N, et al. The anti-BCMA antibody-drug 
conjugate GSK2857916 drives immunogenic cell death and immune-mediated anti-
tumour responses, and in combination with an OX40 agonist potentiates in vivo activity. 
HemaSphere. 2019;1: 231. 
Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO Clinical Practice 
Guidelines for diagnosis, treatment and follow-up. Annals Oncol. 2017; 0:1-11. 

 
CONFIDENTIAL 
 
 
207503 
 
Protocol Amendment 7 JPN-1 
23 Oct 2024 
211 
Moreaux J, Legouffe E, Jourdan E, et al. BAFF and APRIL protect myeloma cells from 
apoptosis induced by interleukin 6 deprivation and dexamethasone. Blood. 
2004;103(8):3148-3157. 
NCCN (National Comprehensive Cancer Network) Multiple myeloma guidelines. 2018. 
https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf (Accessed 3 Sept 
2018). 
NCI. NCI Common Terminology Criteria for Adverse Events, Version 5 (2010) 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Q
uick_Reference_8.5x11.pdf (Accessed 3 Sept 2018). 
New York Heart Association (1994). The Criteria Committee of the New York Heart 
Association (NYHA). Nomenclature and criteria for diagnosis of diseases of the heart 
and great vessels. 9th Ed. Boston, MA:253-256. 
Novak AJ, Darce JR, Arendt BK, et al. Expression of BCMA, TACI, and BAFF-R in 
multiple myeloma: a mechanism for growth and survival. Blood. 2004;103(2):689-694. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol. 1982;5(6):649-655. 
Palumbo A, Avet-Loiseau H, Olivia S, et al. Revised International Staging System for 
Multiple Myeloma: A Report from the International Myeloma Working Group. Clin 
Oncol 2015b 33:2863-2869. 
Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and 
dexamethasone for multiple myeloma. N Engl J Med. 2016;375(8):754-766. 
Palumbo A, Offidani M, Pégourie B, et al. Elotuzumab plus bortezomib and 
dexamethasone versus bortezomib and dexamethasone in patients with 
relapsed/refractory multiple myeloma: 2-year follow-up. Blood. 2015 126:510. 
Papay JI, Clines D, Rafi R, et al. Drug-induced liver injury following positive drug 
rechallenge. Regul Tox Pharm. 2009;54:84-90. 
Pont MJ, Hill T, Cole G, Abbott J, Kelliher J, Salter A, et al. -secretase inhibition 
increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple 
myeloma. Blood. 2019; Doi: 10.1182/blood.2019000050. 
Proskorovsky I, Lewis P, Williams CD, et al. Mapping EORTC QLQ-C30 and QLQ-
MY20 to EQ-5D in patients with multiple myeloma. Health Qual Life Outcomes. 2014 
Mar 11;12:35.  
Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working 
Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 
2014;15(12):e538-548. 

 
CONFIDENTIAL 
 
 
207503 
 
Protocol Amendment 7 JPN-1 
23 Oct 2024 
212 
Reeder CB, Reece DE, Kukreti V, et al. Cyclophosphamide, bortezomib and 
dexamethasone induction for newly diagnosed multiple myeloma: high response rates in 
a phase II clinical trial. Leukemia. 2009 Jul;23(7):1337. 
Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, 
refractory myeloma. N Engl J Med. 2003;348(26):2609-2617. 
Richardson PG, Barlogie B, Berenson J, et al. Extended follow-up of a phase II trial in 
relapsed, refractory multiple myeloma: final time-to-event results from the SUMMIT 
trial. Cancer. 2006;106(6):1316-1319.  
Richardson PG, Hideshima T, Mitsiades C, et al. The emerging role of novel therapies for 
the treatment of relapsed myeloma. J Natl Compr Canc Netw. 2007;5(2):149-162. 
Richardson PG, Rocafiguera AO, Beksac M, et al. Pomalidomide (POM), bortezomib, 
and low‐dose dexamethasone (PVd) vs bortezomib and low-dose dexamethasone (Vd) in 
lenalidomide (LEN)-exposed patients (pts) with relapsed or refractory multiple myeloma 
(RRMM): Phase 3 OPTIMISMM trial. 2018; Abstract #8001; 2018 ASCO Annual 
Meeting, Chicago. 
Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose 
dexamethasone for relapsed multiple myeloma. N Engl J Med. 2005 Jun 
16;352(24):2487-98. 
Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone 
combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010 
Aug 5;116(5):679-686.  
Robinson D, Kaura S, Keily D, Hussein MA, Impact of novel treatments on mutiple 
myeloma survival. Blood. 2014;124:566. 
Sanchez E, Li M, Kitto A, et al. Serum B-cell maturation antigen is elevated in multiple 
myeloma and correlates with disease status and survival. Br J Hematol. 2012;158(6):727-
738. 
Schiffman RM, Christianson MD, Jacobsen G, et al. Reliability and validity of the Ocular 
Surface Disease Index. Arch Ophthalmol. 2000;118(5):615-621. 
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019; 69:7-
34. 
Spencer A, Lentzsch S, Weisel K, et al. Daratumumab plus bortezomib and 
dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple 
myeloma: updated analysis of CASTOR. Haematologica. 2018; 103: 2079-87. 
Tai YT, Anderson KC. Targeting B-cell maturation antigen in multiple myeloma. 
Immunotherapy. 2015;7(11):1187-1199. 

 
CONFIDENTIAL 
 
 
207503 
 
Protocol Amendment 7 JPN-1 
23 Oct 2024 
213 
Tai YT, Li XF, Breitkreutz I, et al. Role of B-cell-activating factor in adhesion and 
growth of human multiple myeloma cells in the bone marrow microenvironment. Cancer 
Res. 2006 ;66(13):6675-6682. 
Tai YT, Mayes PA, Acharya C, et al. Novel anti–B-cell maturation antigen antibody-drug 
conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood. 2014 
May 15;123(20):3128-3138. 
Trudel S, Lendvai N, Popat R, et al. Antibody-drug conjugate, GSK2857916, in 
relapsed/refractory multiple myeloma: an update on safety and efficacy from dose 
expansion phase I study. Blood Cancer J. 2019 Mar 20;9(4):37. 
Trudel S, Lendvai N, Popat R, et al. Targeting B-cell maturation antigen with 
GSK2857916 antibody–drug conjugate in relapsed or refractory multiple myeloma 
(BMA117159): a dose escalation and expansion phase 1 trial. Lancet Oncol. 2018 
Dec;19(12):1641-1653. 
Varfolomeev E, Kischkel F, Martin F, et al. APRIL-deficient mice have normal immune 
system development. Mol Cell Biol. 2004;24(3):997-1006. 
Velcade SmPC (2020). https://www.ema.europa.eu/en/documents/product-
information/velcade-epar-product-information_en.pdf  (Last visited: 4 Dec 2019). 
Velcade USPI (2021). 
https://www.velcade.com/files/pdfs/VELCADE_PRESCRIBING_INFORMATION.pdf  
(Last visited: 22 Jun 2022).  
West CD, Boyd E (2000). Nomogram for Body Surface Area Calculation, modified from 
data of E. Boyd by C.D. West. Nelson textbook of pediatrics (16th ed.). Behrman, RE, 
Kliegman, RM and Jenson, HB. Philadelphia, W.B. Saunders. 
 

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