A Phase II, Open Label, Randomized, Two-Arm Study to Investigate the Efficacy and Safety of Two Doses of the Antibody Drug Conjugate GSK2857916 in Participants With Multiple Myeloma Who Had 3 or More Prior Lines of Treatment, Are Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed an Anti-CD38 Antibody (DREAMM 2)
Phase: PHASE2
Conditions: Multiple Myeloma
Sponsor: GlaxoSmithKline

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TITLE PAGE 
Protocol Title: A Phase II, Open Label, Randomized, Two-Arm Study to Investigate the 
Efficacy and Safety of Two Doses of the Antibody Drug Conjugate GSK2857916 in 
Participants with Multiple Myeloma Who Had 3 or More Prior Lines of Treatment, Are 
Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed 
an Anti-CD38 Antibody (DREAMM 2) 
Protocol Number: 205678/ Amendment 07  
Compound Number: 
GSK2857916  
Brief Title: Open-label, randomized study of two doses of GSK2857916 in participants 
with relapsed/refractory multiple myeloma who have failed prior treatment with an anti-
CD38 antibody 
 
Study Phase: Phase 2 
 
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 
EudraCT number 
2017-004810-25 
 
 
 
Approval Date: 06 Jul 2023 
©2023 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 SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Document Identifier 
Amendment 7 
06 Jul 2023 
TMF-16142696 
Amendment 6 
19-Nov-2021 
TMF-13990464 
Amendment 5 
08-Oct-2020 
2017N330177_06 
Amendment 4 
21-Oct-2019 
2017N330177_05 
Amendment 3 
17-Dec-2018 
2017N330177_04 
Amendment 2 (Republishing) 
04-Sep-2018 
2017N330177_03 
Amendment 2 
30-Aug-2018 
2017N330177_02 
Amendment 1 
02-Apr-2018 
2017N330177_01 
Original Protocol 
18-Jan-2018 
2017N330177_00 
 
 
Amendment 07: 06 Jul 2023 
Overall Rationale for the Amendment: 
This protocol has been amended to update the already existing Post Analysis Continued 
Treatment (PACT) language across the protocol as per the current Sponsor standards. 
Section # and Name Description of Change 
Brief Rationale  
Section 1.1 Synopsis 
Deleted content related to End of 
Treatment and End of Study Definition 
End of Treatment and End of 
Study Definition has changed as 
per the latest PACT template 
language.  
Section 1.2 Schedule 
of Activities (SoA) 
Added additional content to clarify visit 
schedule for PACT phase 
The PACT wording has been 
updated as per the latest GSK 
PACT template language. 
Section 4.1 Overall 
Design 
Added definitions for final analysis and 
EoS. 
The PACT wording has been 
updated as per the latest GSK 
PACT template language. 
Section 4.6 End of 
Study Definition 
Updated the definitions for EoS. 
The PACT wording has been 
updated as per the latest GSK 
PACT template language. 
Section 6 Treatments Added additional content to dosage 
form of belantamab mafodotin as a 
lyophilized powder. 
To allow continued treatment of 
study participants who continue 
to derive clinical benefit post 
final analysis 

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Section # and Name Description of Change 
Brief Rationale  
Section 6.1 
Belantamab 
Mafodotin 
Treatments 
Administered 
Added additional content to dosage 
form of belantamab mafodotin as a 
lyophilized powder. 
To allow continued treatment of 
study participants who continue 
to derive clinical benefit post 
final analysis 
Section 6.8 
Treatment after the 
End of the Study 
This section was deleted and it is 
replaced with a section on Continued 
Access to Study Intervention after the 
End of the Study 
The old PACT language was 
deleted with the new section. 
Section 6.8 
Continued Access to 
Study Intervention 
after the End of the 
Study 
Clarification around treatment following 
end of the study 
The PACT wording has been 
updated as per the latest GSK 
PACT template language. 
Section 6.8.1 
Continued Access to 
Study Intervention 
after the Data Cut-off 
prior to EOS (PACT 
Phase) 
New section is added as per PACT 
Added as per the latest GSK 
PACT template language. 
Section 8.2.1 Time 
Period and 
Frequency for 
collecting AE and 
SAE Information 
Included additional content to align with 
implementation of PACT phase 
The PACT wording has been 
updated as per the latest GSK 
PACT template language. 
 
 

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TABLE OF CONTENTS 
PAGE 
1. 
PROTOCOL SUMMARY .......................................................................................... 9 
1.1. 
Synopsis ....................................................................................................... 9 
1.2. 
Schedule of Activities (SoA) ........................................................................ 17 
2. 
INTRODUCTION .................................................................................................... 31 
2.1. 
Study Rationale .......................................................................................... 31 
2.2. 
Background – BCMA and Multiple Myeloma ............................................... 32 
2.3. 
Antibody-Drug Conjugate Belantamab Mafodotin ....................................... 32 
2.4. 
Human Experience with Belantamab Mafodotin .......................................... 33 
2.4.1. 
Thrombocytopenia ....................................................................... 35 
2.4.2. 
Corneal Events ............................................................................ 35 
2.4.3. 
Infusion-related reactions ............................................................. 35 
2.4.4. 
Pharmacokinetics and Pharmacodynamics .................................. 36 
2.5. 
Benefit / Risk Assessment .......................................................................... 37 
2.5.1. 
Risk Assessment ......................................................................... 37 
2.5.2. 
Benefit Assessment ..................................................................... 41 
2.5.3. 
Overall Benefit-Risk Conclusions ................................................. 41 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 41 
4. 
STUDY DESIGN .................................................................................................... 43 
4.1. 
Overall Design ............................................................................................ 43 
4.2. 
Number of Participants ............................................................................... 48 
4.3. 
Participant Completion ................................................................................ 48 
4.4. 
Scientific Rationale for Study Design .......................................................... 48 
4.5. 
Dose Justification ........................................................................................ 49 
4.6. 
End of Study Definition ............................................................................... 52 
5. 
STUDY POPULATION ........................................................................................... 53 
5.1. 
Inclusion Criteria ......................................................................................... 53 
5.2. 
Exclusion Criteria ........................................................................................ 55 
5.3. 
Lifestyle Restrictions ................................................................................... 57 
5.4. 
Screen Failures........................................................................................... 57 
6. 
TREATMENTS ....................................................................................................... 57 
6.1. 
Belantamab Mafodotin Treatments Administered ........................................ 58 
6.2. 
Dose Modification ....................................................................................... 59 
6.2.1. 
Adjustments Due to Body Weight ................................................ 59 
6.2.2. 
Dose Reductions for Toxicity ....................................................... 59 
6.2.3. 
Corneal Supportive Care Guidelines ............................................ 64 
6.3. 
Method of Treatment Assignment ............................................................... 65 
6.4. 
Blinding ....................................................................................................... 66 
6.5. 
Preparation/Handling/Storage/Accountability .............................................. 66 
6.6. 
Treatment Compliance ................................................................................ 66 
6.7. 
Concomitant Therapy.................................................................................. 67 
6.7.1. 
Permitted Medication(s) ............................................................... 67 
6.7.2. 
Prohibited Medication(s) .............................................................. 67 
6.7.3. 
Prohibited Device(s) .................................................................... 68 
6.8. 
Continued Access to Study Intervention after the End of the Study ............ 68 

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6.8.1. 
Continued Access to Study Intervention After Data Cut-off 
prior to EOS (PACT Phase) ......................................................... 68 
7. 
DISCONTINUATION CRITERIA ............................................................................. 69 
7.1. 
Discontinuation of Study Treatment ............................................................ 69 
7.2. 
Safety Stopping Criteria .............................................................................. 70 
7.2.1. 
Liver Chemistry Stopping Criteria ................................................ 70 
7.2.2. 
Study Treatment Restart or Rechallenge ..................................... 71 
7.2.3. 
Left Ventricular Ejection Fraction (LVEF) Stopping Criteria .......... 71 
7.2.4. 
Corneal Event Stopping Criteria ................................................... 72 
7.2.5. 
Infusion-Related Reaction Management and Stopping 
Criteria ......................................................................................... 72 
7.2.6. 
Allergic and Anaphylactic Reaction Stopping Criteria ................... 72 
7.3. 
Withdrawal from the Study .......................................................................... 73 
7.4. 
Lost to Follow Up ........................................................................................ 73 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 73 
8.1. 
Efficacy Assessments ................................................................................. 76 
8.1.1. 
Independent Review Committee .................................................. 78 
8.2. 
Adverse Events........................................................................................... 78 
8.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 78 
8.2.2. 
Method of Detecting AEs and SAEs ............................................. 80 
8.2.3. 
Follow-up of AEs and SAEs ......................................................... 80 
8.2.4. 
Regulatory Reporting Requirements for SAEs ............................. 80 
8.2.5. 
Cardiovascular and Death Events ................................................ 81 
8.2.6. 
Disease-Related Events and/or Disease-Related ........................ 81 
8.2.7. 
Adverse Events of Special Interest .............................................. 81 
8.2.8. 
Pregnancy ................................................................................... 81 
8.2.9. 
Ocular Examinations and Procedures .......................................... 82 
8.2.10. 
Ocular Sub-Study Examinations .................................................. 83 
8.3. 
Treatment of Overdose ............................................................................... 85 
8.4. 
Safety Assessments ................................................................................... 85 
8.4.1. 
Physical Examinations ................................................................. 86 
8.4.2. 
ECOG Performance Status .......................................................... 86 
8.4.3. 
Vital Signs .................................................................................... 86 
8.4.4. 
Echocardiogram........................................................................... 86 
8.4.5. 
Laboratory Assessments ............................................................. 86 
8.4.6. 
Patient-Reported Outcome Version of the Common Term 
Criteria for Adverse Events (PRO-CTCAE) .................................. 87 
8.4.7. 
Visual Function Questionnaires ................................................... 87 
8.5. 
Pharmacokinetics ....................................................................................... 88 
8.5.1. 
Blood Sample Collection for Pharmacokinetics ............................ 88 
8.5.2. 
Pharmacokinetic Sample Analysis ............................................... 88 
8.6. 
Immunogenicity........................................................................................... 89 
8.7. 
Translational Research ............................................................................... 89 
8.8. 
Genetics ..................................................................................................... 89 
8.9. 
Tumor Biomarker Analysis .......................................................................... 90 
8.9.1. 
sBCMA Sample Analysis ............................................................. 90 
8.9.2. 
Potential Tumor Related Biomarkers ........................................... 90 
8.10. 
Evaluation of Anti-Cancer Activity ............................................................... 91 
8.11. 
Health-Related Quality-of-Life ..................................................................... 91 

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8.11.1. 
European Organization for Research and Treatment of 
Cancer Quality of Life Questionnaire 30-item Core module 
(EORTC QLQ-C30) ..................................................................... 92 
8.11.2. 
European Organization for Research and Treatment of 
Cancer Quality of Life Questionnaire 20-item Multiple 
Myeloma module (EORTC QLQ-MY20) ....................................... 92 
8.11.3. 
Qualitative Telephone Interviews (Patient Interviews) .................. 92 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 93 
9.1. 
Hypothesis Testing ..................................................................................... 93 
9.2. 
Sample Size Determination ........................................................................ 93 
9.3. 
Sample Size Sensitivity ............................................................................... 94 
9.4. 
Populations for Analysis .............................................................................. 95 
9.5. 
Statistical Analyses ..................................................................................... 95 
9.5.1. 
Efficacy Analyses ......................................................................... 95 
9.5.2. 
Safety Analyses ........................................................................... 97 
9.5.3. 
Analyses of Health-Related Quality of Life Data........................... 98 
9.5.4. 
Pharmacokinetic Analyses ........................................................... 98 
9.5.5. 
Pharmacokinetic/Pharmacodynamic Analyses ............................. 99 
9.5.6. 
Translational Research Analyses ............................................... 100 
9.5.7. 
Analyses of Immunogenicity Data .............................................. 100 
9.5.8. 
Other Analyses .......................................................................... 100 
9.5.9. 
Interim Analyses ........................................................................ 101 
10. REFERENCES ..................................................................................................... 104 
11. APPENDICES ...................................................................................................... 109 
11.1. 
Appendix 1: Abbreviations and Trademarks .............................................. 109 
11.2. 
Appendix 2: Clinical Laboratory Tests ....................................................... 114 
11.3. 
Appendix 3: Study Governance Considerations ........................................ 115 
11.4. 
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ..................................... 120 
11.5. 
Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information ................................................................................................ 126 
11.6. 
Appendix 6: Genetics ................................................................................ 129 
11.7. 
Appendix 7: Liver Safety: Required Actions and Follow-up 
Assessments and Study Treatment Rechallenge Guidelines .................... 130 
11.7.1. 
Liver Safety Drug Restart or Re-Challenge Guidelines .............. 132 
11.7.2. 
References ................................................................................ 135 
11.8. 
Appendix 8: ECOG Performance Status ................................................... 136 
11.9. 
Appendix 9: GSK/KVA Scale and Mitigation Strategy for 
Belantamab Mafodotin Treatment-Related Corneal Events ...................... 137 
11.10. Appendix 10: Modified Diet in Renal Disease (MDRD) Formula ................ 140 
11.11. Appendix 11: Protocol Amendment History ............................................... 141 
11.12. Appendix 12: Statistical Considerations for Section 10.5.9.2 
Additional Comparative Futility Stopping Rule Based on Bayesian 
Approach .................................................................................................. 169 
11.13. Appendix 13: Home Healthcare and Telemedicine Approaches ................ 172 
 
 

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LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities - Screening Assessments .................................... 18 
Table 2 
Schedule of Activities – On Study Assessments..................................... 20 
Table 3 
Schedule of Activities: End of Treatment (EOT) and Follow-Up 
Assessments .......................................................................................... 26 
Table 4 
Ocular Sub-Study Schedule of Activities (Selected Sites Only) .............. 30 
Table 5 
Risk Assessment and Mitigation Strategy............................................... 37 
Table 6 
Objectives and Endpoints for Study 205678 - Belantamab 
Mafodotin in RRMM Participants Previously Treated with an Anti-
CD38 Antibody ....................................................................................... 42 
Table 7 
Summary of Investigator-Assessed Best Response (with 
Confirmation; Study BMA117159 Part 1) ................................................ 50 
Table 8 
Summary of Predicted Mean Response and Mean ≥Grade 2 
Corneal Event* and 95% Credible Intervals (Parts 1 and 2, Study 
BMA117159) .......................................................................................... 52 
Table 9 
Criteria for Determining Adequate Organ System Function .................... 54 
Table 10 
Permitted Dose Reductions .................................................................... 59 
Table 11 
Dose Modification Guidelines for Belantamab Mafodotin-Related 
Adverse Events ...................................................................................... 60 
Table 12 
General Dose Modification and Management Guidelines for 
Drug- related Adverse Events Not Otherwise Specifieda ........................ 62 
Table 13 
Dose Modification Guidelines for Belantamab Mafodotin 
Treatment-Related Corneal Events ........................................................ 63 
Table 14 
List of Clinical Laboratory Tests ............................................................. 75 
Table 15 
Statistical Power Scenarios .................................................................... 94 
Table 16 
Analysis Populations Defined for the Study ............................................ 95 
Table 17 
Statistical Analysis Methods for Efficacy Endpoints ................................ 96 
Table 18 
Statistical Analysis Methods for Safety Endpoints .................................. 98 
Table 19 
Probabilities of Crossing Boundaries at the Interim or Final ORR 
Analysis based on Group Sequential Design ........................................ 101 
Table 20 
Probabilities of Stopping for Futility at the Interim or Claiming 
Efficacy at the Final ORR Analysis based on Both Futility Rules .......... 102 

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Table 21 
Prophylactic Measures for Corneal Events Associated with 
Belantamab Mafodotin a ....................................................................... 138 
Table 22 
GSK/KVA Scale for Corneal Events Associated with Belantamab 
Mafodotin a ........................................................................................... 138 
Table 23 
Guidance on GSK/KVA Scale Grading Based on Changes in 
Visual Acuity ........................................................................................ 139 
Table 24 
Posterior Probabilities of (Arm 1 Response Rate > Arm 2 
Response Rate) at Interim Analyses .................................................... 170 
Table 25 
Scenarios of Simulation Studies to Evaluate Probabilities of 
Stopping for Futility .............................................................................. 171 
 
LIST OF FIGURES 
PAGE 
Figure 1 
Study 205678 Schematic ....................................................................... 45 
Figure 2 
Fitted Dose-Response Plot for ORR and ≥ Grade 2 Corneal 
Event Rate ............................................................................................. 51 
Figure 3 
Liver Chemistry Stopping Criteria – Liver Stopping Event 
Algorithm ................................................................................................ 71 
Figure 4 
Ocular prophylaxis schematic ................................................................. 84 

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1. 
PROTOCOL SUMMARY  
1.1. 
Synopsis 
Protocol Title: A Phase II, Open Label, Randomized, Two-Arm Study to Investigate the 
Efficacy and Safety of Two Doses of the Antibody Drug Conjugate GSK2857916 in 
Participants with Multiple Myeloma Who Had 3 or More Prior Lines of Treatment, Are 
Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed 
an Anti-CD38 Antibody (DREAMM 2) 
Short Title: Open-label, randomized study of two doses of GSK2857916 in participants 
with relapsed/refractory multiple myeloma who have failed prior treatment with an anti-
CD38 antibody. 
Rationale: Multiple myeloma (MM) is an incurable malignancy and accounts for 1% of 
all cancers and for 10% of all hematologic malignancies. Worldwide, approximately 
103,000 new cases are diagnosed annually, and an estimated 30,330 new cases and 
12,650 deaths will occur in the US in 2016. Despite significant advances in treatment 
options, including hematopoietic stem cell transplant (HSCT), and novel therapies like 
second- and third-generation proteasome inhibitors (PIs), immunomodulatory agents, and 
recent addition of monoclonal antibodies (mAbs), most MM patients will ultimately 
develop resistance to existing therapies and die of relapse.  
One such novel therapy, daratumumab, is a human IgGk monoclonal antibody that was 
granted first approval in the US in November 2015. Daratumumab binds with high 
affinity to the CD38 molecule, which is highly expressed on the surface of MM cells. It is 
believed to induce rapid tumor cell death through apoptosis, and multiple immune-
mediated mechanisms, including complement-dependent cytotoxicity, antibody-
dependent cellular phagocytosis and antibody-dependent cellular cytotoxicity.  
Daratumumab is approved by the FDA for the treatment of MM in combination with 
lenalidomide and dexamethasone, or bortezomib and dexamethasone in patients who 
have received at least one prior therapy, in combination with pomalidomide and 
dexamethasone in patients who have received at least two prior therapies including 
lenalidomide and a proteasome inhibitor (PI), and as monotherapy for the treatment of 
patients who have received at least three prior lines of therapy, including a PI and an 
immunomodulatory agent, or who are double-refractory to a PI and an 
immunomodulatory agent.  
In Europe, daratumumab is approved for the treatment of MM in combination with 
lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of 
patients who have received at least one prior therapy and as monotherapy for the 
treatment of patients with relapsed and refractory MM, whose prior therapy included a PI 
and an immunomodulatory agent and who have demonstrated disease progression on the 
last therapy. Patients with MM who have proven refractory to daratumumab mono- and 
combination therapy, have few treatment options available, and could benefit 
significantly from treatment with a next-generation regimen, such as GSK2857916, 
belantamab mafodotin. 

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Belantamab mafodotin is a humanized (IgG1) antibody-drug conjugate (ADC) which 
binds to BCMA, a target widely expressed on malignant plasma cells in MM. The parent 
anti-BCMA antibody is conjugated to the microtubule inhibitor, MMAF, which is 
released inside the malignant cell after binding and internalization of the antibody. The 
normal function of BCMA is to promote cell survival by transduction of signals from two 
known ligands: B-cell activating factor from the tumor necrosis factor (TNF) family 
(BAFF/BLyS), and APRIL, a proliferation-inducing ligand.  
In addition, preclinical experiments indicate that belantamab mafodotin has the potential 
to induce immunogenic cell death (ICD) in a BCMA-expressing multiple myeloma cell 
line. Exposure of dendritic cells to tumor cells undergoing ICD induces an antigen-
specific T cell response, which may help to exert anti-tumor effects.  
Preliminary clinical data from the ongoing BMA117159 study as of 26 June 2017 (n=35 
participants treated at 3.4 mg/kg) has demonstrated an ORR of 60% [95% CI: 42.1%, 
76.1%], (complete response: 6%, very good partial response [VGPR] 43%, partial 
response [PR] 9%), with 51% of participants (N = 18/35) having deep responses of 
VGPR or better, in heavily pretreated participants with relapsed/refractory multiple 
myeloma (RRMM). The median duration of response (DoR) has not been achieved, the 
25th percentile for DoR is 6.7 months; the median PFS in this population was 7.9 months 
[95% CI: 3.1, NA]. The number of prior therapies ranged from 1-13 with 71% of 
participants reporting greater than or equal to 4 prior therapies. For the 14 (40%) 
participants who had received prior daratumumab, the ORR was 43%, (95% CI: 17.7%, 
71.1%; CR: 0, VGPR: 21%; PR: 14%).  
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 order to generate additional safety and 
efficacy data at a lower dose while providing participants a chance of deriving clinical 
benefit, the dose of 2.5 mg/kg has been selected for testing in an additional arm in this 
study. The two-arm design with two dose levels and a futility analysis is justified for this 
population because there is no approved comparator for the proposed treatment setting.  
Objectives and Endpoints 
Objectives 
Endpoints 
Primary Objective 
To evaluate the clinical efficacy of 2 
doses of belantamab mafodotin in 
participants with relapsed/refractory 
multiple myeloma. 
ORR, defined as the percentage of participants with a confirmed 
partial response (PR) or better (i.e., PR, very good partial 
response [VGPR], complete response [CR] and stringent 
complete response [sCR]), according to the 2016 International 
Myeloma Working Group (IMWG) Response Criteria by 
Independent Review Committee (IRC). 
Secondary Objectives 
To further evaluate the clinical 
measures of efficacy of belantamab 
mafodotin in participants with RRMM 
 
 
ORR, defined as the percentage of participants with a confirmed 
partial response (PR) or better, according to the 2016 
International Myeloma Working Group (IMWG) Response 
Criteria by investigator assessment 
 

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Objectives 
Endpoints 
Clinical benefit rate (CBR), defined as the percentage of 
participants with a confirmed minimal response (MR) or better 
according to the 2016 International Myeloma Working Group 
(IMWG) Response Criteria  
 
Duration of response (DoR), defined as: the time from first 
documented evidence of PR or better until the earliest date of 
documented disease progression (PD) per IMWG; or death due 
to PD occurs among participants who achieve an overall 
response, i.e., confirmed PR or better. 
 
Time to response, defined as the time between the date of 
randomization and the first documented evidence of response 
(PR or better). 
 
Progression-free survival, defined as the time from 
randomization until the earliest date of documented disease 
progression (PD) per IMWG, or death due to any cause. 
 
Time to progression, defined as the time from randomization 
until the earliest date of documented PD per IMWG, or death 
due to PD. 
 
Overall survival, defined as the time from randomization until 
death due to any cause. 
To evaluate the safety of belantamab 
mafodotin in participants with RRMM. 
The safety profile of belantamab mafodotin will be evaluated in 
participants with RRMM as assessed through: 
standard clinical and laboratory tests (hematology and 
chemistry, physical examination, vital sign measurements, and 
diagnostic tests) 
through the collection of adverse events (AEs) and serious 
adverse events (SAEs) 
AEs of special interest 
ocular findings on ophthalmic exam 
To evaluate the pharmacokinetic 
profile of belantamab mafodotin 
Plasma concentrations of belantamab mafodotin (ADC, total 
mAb, and cys-mcMMAF) 
Derived pharmacokinetic parameter values (e.g., AUC, Cmax, 
tmax, t½), as data permit. 
To assess anti-drug antibodies 
(ADAs) against belantamab mafodotin 
Incidence and titers of ADAs against belantamab mafodotin 
Participant self-reported symptomatic 
adverse effects by evaluation of 
tolerability of belantamab mafodotin 
Symptomatic adverse effects and related impacts as measured 
by the PRO-CTCAE, NEI-VFQ-25 and OSDI 
To evaluate disease and treatment 
related symptoms and impact on 
function and health-related quality-of-
life 
Health-related quality-of-life as measured by the EORTC QLQ-
C30 and EORTC QLQ-MY20 
Exploratory Objectives 
To explore the relationship between 
clinical response and other biologic 
characteristics including BCMA 
Determine BCMA expression levels and other markers on 
malignant cells, serum sBCMA levels, and evaluate the 
relationship of these factors to clinical response 

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Objectives 
Endpoints 
expression on tumor cells and sBCMA 
concentrations  
To investigate the relationship 
between genetic variants in the host 
and response to belantamab 
mafodotin  
Possible relationship between host genetic variation and 
response to belantamab mafodotin 
To evaluate disease and treatment 
related symptoms and impact on 
function and health-related quality-of-
life 
Qualitative telephone interview(s) 
To explore exposure-response 
relationships between belantamab 
mafodotin exposure and clinical 
endpoints 
Explore relationships between belantamab mafodotin exposure 
(e.g., dose, dose intensity, concentration, Cmax, or AUC) and 
clinical endpoints (e.g., response, corneal event), if data permit 
To assess Minimal Residual Disease 
(MRD) in participants who achieve 
≥VGPR or better 
Minimal Residual Disease (MRD) negativity rate, defined as: the 
percentage of participants who are MRD negative by Next 
Generation Sequencing (NGS). 
To assess the safety, efficacy, 
immunogenicity, and 
pharmacokinetics of belantamab 
mafodotin in a lyophilized 
configuration (n= Approximately 25 
participants) 
AEs, clinical and laboratory assessments; Descriptive analyses 
of ORR, duration of response, time to response, time to 
progression, overall response; incidence and titers against 
belantamab mafodotin; plasma concentrations of belantamab 
mafodotin (ADC, total mAb, and cys-mcMMAF) and derived 
pharmacokinetic parameters, if data permit 
Ocular sub-study objective 
To evaluate the effect of topical 
corticosteroids on corneal findings in 
approximately 30 participants who will 
receive monocular topical 
corticosteroids for the first 4 cycles 
Description of differences in corneal findings in each eye based 
on ophthalmic examinations (participant-level). 
Abbreviations: IV = intravenous; Q3W: once every 3 weeks; RRMM = relapsed refractory multiple myeloma; BCMA = 
B-cell maturation antigen; MMAF = monomethyl auristatin-F; MRD = minimal residual disease; NGS = Next Generation 
Sequencing; ORR = overall response rate; CI = confidence interval; CR = complete response; VGPR = very good 
partial response; PR = partial response; PFS = progression free survival; AUC = area under the curve; Cmax = 
maximum concentration; tmax = time to maximum; t½ = half-life; PRO-CTCAE = Patient Reported Outcomes-Common 
Terminology Criteria for Adverse Events; NEI-VFQ-25 = National Eye Institute Visual Functioning Questionnaire 25; 
OSDI = Ocular Surface Disease Index; EORTC = European Organisation for Research and Treatment of Cancer; 
QLQ-C30 = Quality of Life Questionnaire 30-item Core module; FLC = free light chain; SCT = stem cell transplant; 
QLQ-MY20 = ; Quality of Life Questionnaire 20-item module for MM; QTcF = QT interval corrected by Fridericia's 
formula; HIV = human immune deficiency virus; RNA = ribose nucleic acid. 
 
Overall Study Design: This is a Phase II, open-label, two-arm, randomized, multicenter 
study to evaluate the efficacy and safety of belantamab mafodotin monotherapy at the 
dose levels of 2.5 mg/kg and 3.4 mg/kg administered intravenously (IV), Q3W, in 
participants with RRMM. Participants will be treated until disease progression or 
unacceptable toxicity. The study consists of a screening/baseline period, a treatment 
period, and a post-treatment follow-up period.  
The design includes an independent cohort of approximately 25 additional participants 
who will receive a lyophilized configuration of belantamab mafodotin. Participants in the 
main study will receive a frozen liquid solution of belantamab mafodotin. Assessments 

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will be performed during Screening, prior to the first dose of Cycle 1, and during each 
cycle of treatment as illustrated in the Schedule of Activities. 
The study will include 1 interim analysis for futility. If one arm is discontinued as a result 
of the interim analysis, participants will be offered the opportunity to receive treatment at 
the dose that is continuing, or at the original dose upon re-consenting.  
As part of an ocular sub-study, approximately 30 participants (~15 per dose level) will be 
evaluated to study the effect of ophthalmic topical corticosteroids on belantamab 
mafodotin-associated corneal findings and to further characterize these findings. 
Following 39 months post last subject first dose (LSFD), the study will move into the 
post analysis continued treatment (PACT) phase where the study remains open only to 
provide continued access to treatment for study participants who are continuing to derive 
clinical benefit. At that time, the collection of new data for participants who no longer 
receive study treatment will stop and the clinical trial database will be closed. Participants 
in survival follow-up will be considered to have completed the study. Those participants 
still benefiting from study drug in the opinion of their treating physician may continue to 
receive study drug and only SAEs, AEs leading to treatment discontinuation, overdose 
and pregnancy cases, and pre-specified ocular data will be reported directly to GSK using 
paper forms. The end of study (EOS) is defined as the date of the last visit of the last 
participant in the study. 
 
Number of Participants: The sample size calculation was performed using East 6.4 
software as a starting point, based on the ORR comparison between the belantamab 
mafodotin arm and the historical control. Based on the simulation results with the 
planned sample size of 65 participants there is 86.90% power to reject the null hypothesis 
within each arm with a 1-sided type I error of 1.23%. 
Approximately 170 participants were initially planned to be screened to enroll a 
minimum of 155 participants at approximately 60 investigational sites globally. A 
minimum of 130 participants (65/arm) were planned to be enrolled to 2 arms receiving 
frozen liquid solution of belantamab mafodotin, which includes ~30 participants from the 
ocular sub-study. Approximately 200 participants will be enrolled onto the frozen liquid 
portion of the study.  
Approximately, twenty-five additional participants will be enrolled into the independent 
lyophilized drug product cohort. 
Treatment Groups and Duration: In this two-arm randomized study, belantamab 
mafodotin will be administered at 2 dose levels (2.5 mg/kg or 3.4 mg/kg) to participants 
by IV infusion on the Q3W schedule at the study site. The dose will be based on actual 
body weight calculated at baseline and may be reduced to address toxicities according to 
protocol guidelines. 
Belantamab mafodotin will be administered on Day 1 of each cycle. Premedication is not 
required unless deemed medically necessary by the investigator, in which case it should 

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be administered according to institutional recommendations. If an infusion-related 
reaction (IRR) occurs during administration, the infusion rate may be reduced or halted at 
the discretion of the investigator depending on the severity of the symptoms.  
Participants will be treated until disease progression or until unacceptable toxicity.  
Inclusion Criteria: Participants are eligible to be included in the study only if all the 
following criteria apply: 
1. Provide signed written informed consent, which includes compliance with the 
requirements and restrictions listed in the consent form 
2. Male or female, 18 years or older (at the time consent is obtained)  
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 
4. Histologically or cytologically confirmed diagnosis of MM as defined in IMWG, 
2014 criteria, and  
a. Has undergone stem cell transplant or is considered transplant ineligible, and 
 
b. Has failed at least 3 prior lines of anti-myeloma treatments, including an anti-
CD38 antibody (e.g., daratumumab) alone or in combination, and is refractory 
to an immunomodulatory agent (i.e., lenalidomide or pomalidomide), and to a 
proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib). 
Refractory myeloma is defined as disease that is nonresponsive while on 
primary or salvage therapy, or progresses within 60 days of last therapy. 
Nonresponsive disease is defined as either failure to achieve at least minimal 
response or development of progressive disease (PD) while on therapy. 
 
5. Has measurable disease with at least one of the following: 
a. Serum M-protein 0.5 g/dL (5 g/L) 
b. Urine M-protein 200 mg/24h 
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) 
6. Participants with a history of autologous stem cell transplant are eligible for study 
participation provided the following eligibility criteria are met: 
a. transplant was >100 days prior to study enrolment 
b. no active infection(s) 
c. participant meets the remainder of the eligibility criteria outlined in this 
protocol 
7. Adequate organ system function. 
8. Female Participants: Contraceptive use by men or women should be consistent with 
local regulations regarding the methods of contraception for those participating in 
clinical studies.  
 

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A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one 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, during the 
intervention period and for at least 80 days after the last dose of study 
intervention 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. 
 
A WOCBP must have a negative highly sensitive serum pregnancy test (as 
required by local regulations) within 72 hours before the first dose of study 
intervention.  
 
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. 
9. Male Participants: Contraceptive use by men or women 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 during the 
intervention period and for at least 140 days:  
• 
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 and female partner to use an additional highly 
effective contraceptive method with a failure rate of <1% per year as when 
having sexual intercourse with a woman of childbearing potential who is not 
currently pregnant.  
10. All prior treatment-related toxicities (defined by National Cancer Institute- Common 
Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03 must be ≤Grade 1 
at the time of enrolment except for alopecia and Grade 2 peripheral neuropathy. 

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11. In France, a participant will be eligible for inclusion in this study only if either 
affiliated to or a beneficiary of a social security category. 
 
Exclusion Criteria: Participants satisfying any of these criteria are not eligible for 
assignment to treatment: 
1. Systemic anti-myeloma therapy within ≤14 days or 5 half-lives, whichever is shorter, 
or plasmapheresis within 7 days prior to the first dose of study drug 
2. Systemic treatment with high dose steroids (equivalent to 60 mg prednisone daily 
for ≥4 days) within the past 14 days if administered to treat MM or non- MM disease 
3. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, 
organomegaly, endocrinopathy, myeloma protein, and skin changes), active plasma 
cell leukemia at the time of screening. 
4. Prior allogeneic stem cell transplant (SCT)  
5. Current corneal epithelial disease except mild punctate keratopathy  
6. Use of an investigational drug within 14 days or five half-lives, whichever is shorter, 
preceding the first dose of study drug. Prior treatment with a monoclonal antibody 
within 30 days of receiving the first dose of study drugs. Prior BCMA targeted 
therapy.  
7. Evidence of active mucosal or internal bleeding 
8. Any major surgery within the last four weeks 
9. 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 entry criteria. 
10. 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.  
11. Current unstable liver or biliary disease per investigator assessment defined by the 
presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or 
gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease 
(including Gilbert’s syndrome or asymptomatic gallstones) or hepatobiliary 
involvement of malignancy is acceptable if participant otherwise meets entry criteria. 
12. Malignancies other than disease under study are excluded, except for any other 
malignancy from which the participant has been disease-free for more than 2 years 
and, in the opinion of the principal investigators and GSK Medical Monitor, will not 
affect the evaluation of the effects of this clinical trial treatment on the currently 
targeted malignancy (MM). Participants with curatively treated non-melanoma skin 
cancer may be enrolled. 
13. Evidence of cardiovascular risk including any of the following: 
a. 
 QTcF interval QTcF > 480 msec (the QT interval values must be corrected 
for heart rate by Fridericia’s formula [QTcF]) 

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b. Evidence of current clinically significant uncontrolled arrhythmias, including 
clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd 
degree atrioventricular (AV) block. 
c. 
History of myocardial infarction, acute coronary syndromes (including 
unstable angina), coronary angioplasty, or stenting or bypass grafting within 
six months of Screening. 
d. Class III or IV heart failure as defined by the New York Heart Association 
functional classification system 
e. 
Uncontrolled hypertension 
14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs 
chemically related to belantamab mafodotin, or any of the components of the study 
treatment. 
15. Pregnant or lactating female. 
16. Active infection requiring antibiotic, antiviral, or antifungal treatment. 
17. Known HIV infection. 
18. Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody 
(HBcAb at screening or within 3 months prior to first dose of study treatment) 
19. 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.  
Note: Participants with positive Hepatitis C antibody due to prior resolved disease 
can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. 
Note: Hepatitis RNA testing is optional and participants with negative Hepatitis C 
antibody test are not required to also undergo Hepatitis C RNA testing. 
 
1.2. 
Schedule of Activities (SoA) 
All assessments planned for participants in Study 205678 are shown in Table 1 
(Screening), Table 2 (On Study Assessments), and Table 3 (End of Treatment and Follow 
Up Assessments).  
Assessments for participants in the ocular sub-study are shown in Table 4. Participants 
who are enrolled into the lyophilized configuration cohort of belantamab mafodotin 
(Figure 1) will follow the same assessments and procedures as the main study.  
The details of these assessments are provided in footnotes to the table, with more details 
provided in Section 8. 
PACT Phase: Participants who continue to receive study treatment during the PACT 
phase will be monitored and receive follow-up care in accordance with standard local 
clinical practice at the participant’s particular study site. Only SAEs, AEs leading to 
discontinuation of study treatment, overdoses, prespecified ocular data, and pregnancy 
cases will be reported directly to the Sponsor via paper forms (see Section 8.2.1 and refer 
to the SRM). For participant discontinuing treatment in the PACT phase, no end of 
treatment visit is required. 

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Table 1 
Schedule of Activities - Screening Assessments 
Study Assessments1 
Screen1 
Notes 
Informed Consent 
X 
1. 
All Screening assessments must be performed within 21 days prior to first dose unless otherwise specified. Informed Consent 
must be signed before any study-specific assessments are performed. Screening Assessment do not need to be repeated on 
Day 1 of Cycle 1 (C1D1) unless otherwise specified. 
2. 
All related SAEs are to be collected from consent through OS follow-up 
3. 
Screening examination to be performed within 21 days prior to first dose. See Section 8.2.9 for the list of screening ophthalmic 
exam procedures. 
4. 
Refer to Table 14 for a comprehensive list of clinical laboratory tests that must be collected for all participants. If labs are 
completed within 72 hours prior to the first dose, this assessment need not be repeated on C1D1 
5. 
Albumin/Creatinine ratios (spot urine from first void) at screening, C1, and every other cycle thereafter (C3, C5, C7) (local labs or 
central if local not available) 
6. 
Hepatitis: If the participant is hepatitis C virus (HCV) positive by serology, an additional Hep C RNA testing may be done to 
determine participant eligibility (if Hep C RNA is negative, participant is eligible).  
7. 
Troponin I will be measured at the local lab, or by central laboratory if not available locally. If cardiac workup is required due to 
safety concerns during the study, troponin I should be measured as clinically indicated. 
8. 
B-type natriuretic peptide (BNP) to be measured locally, or by a central laboratory if not available locally, at screening; if cardiac 
workup is required due to safety concerns during the study, BNP should be measured as clinically indicated. 
9. 
Perform only in women of child-bearing potential. A serum pregnancy test must be performed  
at screening, and subsequent pregnancy tests may be either serum or urine. If test is completed within 72 hours prior to the first 
dose, this assessment need not be repeated on Day 1 of Cycle 1. For questionable cases of whether a participant is of non-child 
bearing potential, obtain follicle stimulating hormone (FSH) and estradiol. See Section 5.1, Section 8.2.8, and Appendix 5 for 
more details. 
10. Echocardiography for LVEF performed within 35 days prior to first dose is acceptable as screening value.  
11. Skeletal Survey: Imaging of bones for lytic lesions by a method aligned with the institutional guidance (ex: X-ray, CT, or MRI). 
Skeletal survey results within 30 days prior to C1D1 are acceptable. For sites in Germany: Only MRI is allowed to be used as 
imaging modality for participants.  
12. Imaging is only required for participants with extramedullary disease (CT, MRI, or PET/CT can be applied per local guidance). 
Screening assessment may be performed up to 30 days prior to C1D1. The same modality should be used throughout the study 
Baseline Demographics 
X 
Medical History including 
disease history and 
characteristics 
X 
Physical Exam 
X 
Concomitant Medications 
X 
Adverse Events 2 
X 
Safety 
Ocular Exam3 
X 
ECOG Performance Status 
X 
Vital Signs (BP, HR, Body 
Temperature) 
X 
Weight and Height 
X 
Hematology4 
X 
Clinical chemistry4 
X 
Urine Dipstick4 
X 
eGFR (by MDRD formula- see 
Appendix 10) 
X 
Spot Urine (albumin/creatinine 
ratio)4, 5 
X 
CRP 
X 
HBsAg, HBcAb, and hepatitis 
C Ab. 6 
X 
Troponin I7 
X 
BNP8 
X 
Pregnancy Test 9 
X 
ECHO10 
X 
12-lead ECG 
X 

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Study Assessments1 
Screen1 
Notes 
Disease Evaluation 
(i.e., if CT scan was used as baseline, participant needs to be followed by CT scans). 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 skin only 
involvement, skin lesions should be measured with a ruler. Measurement of tumor size will be determined by the Sum of the 
Products of the maximal perpendicular diameters of measured lesions (SPD). Digital copies of all scans must be maintained at 
the investigator site as source document. For sites in Germany: Only MRI is allowed to be used as imaging modality for 
participants with extramedullary disease. 
13. Only required for participants with IgD/E myeloma, where serum m-component cannot be followed otherwise. 
14. FISH testing at least for: t (4;14), t (14;16), and 17p13del. FISH results from samples taken within 60 days prior to first dose are 
acceptable. If testing cannot be performed at a local lab, a bone marrow aspirate can be sent to central lab for analysis. If the 
patient is known to have high risk disease from previous FISH tests regardless of timing (i.e.: t(4;14), or t(14;16) they should be 
stratified as High Risk for the purpose of enrollment.  
15. Minimal residual disease (MRD) to be performed by the central lab at screening, at the time of first achieving VGPR or CR, 
repeat MRD testing 6 mo and 12 mo after achieving VGPR or CR (provided VGPR/CR is maintained).  
16. Bone Marrow (aspirate preferred) for disease assessment performed within the screening period prior to first dose is acceptable. 
 
 
Beta2 microglobulin 
X 
Skeletal survey11 
X 
Imaging for Extramedullary 
disease12 
X 
UPEP (Urine Protein 
Electrophoresis) 24 hr. urine 
collection 
X 
Urine immunofixation 
X 
SPEP (Serum Protein 
Electrophoresis) 
X 
Serum Immunofixation 
X 
Serum Kappa, Lambda free 
Light chain, FLC ratio 
X 
Calcium corrected for albumin 
(serum) 
X 
IgG, IgM, IgA 
X 
IgD/E13 
X 
Bone Marrow (BM) Aspiration/Biopsy 
BM for FISH 14 
X 
BM aspirate for BCMA IHC 
assessment 
X 
BM for MRD testing15 
X 
BM for disease assessment16 
X 
Health Outcomes 
PRO-CTCAE 
X 
NEI-VFQ-25 
X 
OSDI 
X 
BM = bone marrow; BNP = B-type natriuretic peptide; BP = blood pressure; C1D1 = Cycle 1 Day 1, etc. CRP = C-reactive protein; FISH = fluorescence in situ hybridization; FLC = free 
light chain; HR= heart rate; Ig = immunoglobulin; NEI-VFQ-25 = National Eye Institute Visual Functioning Questionnaire 25; OSDI = Ocular Surface Disease Index; PRO-CTCAE = 
Patient Reported Outcome version of the Common Term Criteria for Adverse Events; PD = Progressive Disease; SPEP = serum protein electrophoresis; UPEP = urine protein 
electrophoresis. 
 

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Table 2 
Schedule of Activities – On Study Assessments  
Study 
Assessments 
Cycle 1, 
Day 11  
Cycle 1 
& 
Cycle 3 
Day 4 
Cycle 1 
&  
Cycle 3, 
Day 8-15
Q3W 
starting 
Wk 42 (to be 
performed 
regardless 
of dosing) 
Cycle 2-
CX with 
dosing 2 
Notes 
Physical Exam 
X 
 
 
X 
 
(Important: Every participant will complete Cycle 1 Day 1 on study assessments. Then, 
they will complete ‘Q3W’ assessments starting at week 4’ AND the ’Cycle 2-CX with 
dosing’ assessments during the treatment phase). If dosing is not completed only 
perform the “Q3W starting at Week 4” assessments at the scheduled visit.  
1. 
Assessments scheduled on days of dosing must be done prior to drug administration, unless 
otherwise specified. All other assessments can be done 3 days unless otherwise specified. 
2. 
Belantamab mafodotin will be administered intravenously on Day 1 (D1) of every 21-day 
cycle (Q3W) until disease progression, unacceptable toxicity, death or withdrawal of consent.  
3. 
All related SAEs are to be collected from consent through OS follow-up  
4. 
On-study ophthalmic exams to be performed by an ophthalmologist (or an optometrist if an 
ophthalmologist is not available) predose every 3 weeks. See Section 8.2.9 for the list of 
ophthalmic exam procedures. If there are no corneal signs per the GSK/KVA Scale for 
treatment related corneal events at time of the cycle 4 exam, participants may have their 
ophthalmologic exams decreased to once every 3 months. If a participant subsequently 
develops ocular symptoms, the participant should be evaluated by an ophthalmologist (an 
optometrist if an ophthalmologist is not available). Intraocular pressure must be monitored if 
steroid eye drops are used continuously for more than 7 days. Additional exams may be 
performed by the ophthalmologist (an optometrist if an ophthalmologist is not available), as 
clinically indicated. At selected sites, participants will undergo additional ophthalmic exams. If 
you are a selected site, see Section 8.2.9 for full list of ocular sub-study exam procedures. 
5. 
If a participant’s belantamab mafodotin dose is not administered at a given visit, the following 
activities do not need to be performed at that visit unless clinically indicated: Vitals, weight, 
spot urine, pregnancy test, ECG, PK sample, ADA sample, and soluble BCMA sample.  
Adverse Events3 
Ongoing 
 
 
Ongoing 
Ongoing 
Concomitant 
Medications 
Ongoing 
 
 
Ongoing 
Ongoing 
Safety 
Ocular Exam4 
 
 
 
X 
 
ECOG 
Performance Status 
 
 
 
X 
 
Vital Signs (BP, 
HR, Body 
Temperature)5, 6  
X 
 
 
 
X 
Weight5  
Weight 
Only 
 
 
 
Weight 
Only 
Hematology 7 
X 
 
 
X 
 
Clinical chemistry 7 
X 
 
 
X 
Urine Dipstick 7 
X 
 
 
X 
 
eGFR (by MDRD 
formula- see 
Appendix 10) 
X 
 
 
X 
 
Spot urine for 
albumin/creatinine 
ratio5, 7, 8 
X 
 
 
 
X 
CRP 
 
 
 
X 
 
Pregnancy Test 5, 9 
 
 
 
 
X 
ECHO 
 
 
 
As clinically 
indicated 
 

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Study 
Assessments 
Cycle 1, 
Day 11  
Cycle 1 
& 
Cycle 3 
Day 4 
Cycle 1 
&  
Cycle 3, 
Day 8-15
Q3W 
starting 
Wk 42 (to be 
performed 
regardless 
of dosing) 
Cycle 2-
CX with 
dosing 2 
Notes 
12-lead ECG 5,10 
 
 
 
 
As 
clinically 
indicated 
6. 
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 
minutes prior to start of infusion(SOI)), +10 minutes after SOI, within ±5 minutes of end of 
infusion (EOI), and 1-hour (±5 minutes) post EOI. On subsequent dosing days, vital signs 
must be assessed at pre-dose (within 30 minutes prior to SOI), within ±5 minutes of EOI. On 
days where vital sign time points align with PK sampling time points, it is recommended that 
vital signs be assessed prior to PK samples being drawn. On days where vital signs are 
measured multiple times, temperature does not need to be repeated unless clinically 
indicated.  
7. 
Refer to Table 14 for a comprehensive list of lab tests that must be collected for all 
participants. If labs are completed within 72 hours prior to the first dose, this assessment 
need not be repeated on C1D1. More frequent hematologic monitoring is recommended for 
subjects with thrombocytopenia and/or neutropenia who are receiving treatment. See Table 
11 for further details.  
8. 
Albumin / creatinine ratios (spot urine from first void) at, C1, and every other cycle thereafter 
(C3, C5, C7, etc.) (use local labs; use central labs if local not available) 
9. 
Perform only in women of child-bearing potential. A serum pregnancy test must be performed 
at screening, and subsequent pregnancy tests may be either serum or urine. If test is 
completed within 72 hours prior to the first dose, this assessment need not be repeated on 
C1D1. For questionable cases of whether a participant is of non-child bearing potential, 
obtain follicle stimulating hormone (FSH) and estradiol. See Section 5.1, Section 8.2.8, and 
Appendix 5 for more details. 
10. ECGs previously collected and stored centrally may be reviewed by an independent central 
reviewer. ECGs performed as clinically indicated will be kept locally. See SRM for details on 
collection regarding ECGs. 
11. PK samples to be taken in all participants for belantamab mafodotin measurement during 
Cycle 1, Day 1 and Cycle 3, Day 1 at the following study times: predose (within 30 minutes 
prior to SOI), at EOI (5 min), at 2 h (±15 min) after SOI, and at 24 h (±2 hrs) after SOI. 
Pharmacokinetics 
PK5,  
X11 
X12 
X13 
 
X14 
Anti-drug 
antibodies5, 15 
X 
 
 
 
X 
Disease Evaluation 
Response 
assessment16 
 
 
 
X 
 
Skeletal Survey 17 
 
 
 
As clinically 
indicated 
 
Imaging for 
Extramedullary 
disease18 
 
 
 
Week 13, 
25, 37, 49, 
and then 
every 12 
weeks within 
the first 12 
months; 
thereafter 
only if 
clinically 
indicated 
 
PET/CT upon 
achieving CR or 
sCR19 
 
 
 
Once after 
CR or sCR 
 
UPEP (Urine 
Protein 
Electrophoresis) 24 
hr. urine collection 
 
 
 
X 
 

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Study 
Assessments 
Cycle 1, 
Day 11  
Cycle 1 
& 
Cycle 3 
Day 4 
Cycle 1 
&  
Cycle 3, 
Day 8-15
Q3W 
starting 
Wk 42 (to be 
performed 
regardless 
of dosing) 
Cycle 2-
CX with 
dosing 2 
Notes 
Urine 
Immunofixation 
 
 
 
By central 
lab if UPEP 
is negative, 
at the time of 
first 
achieving 
CR then 
perform 
every 3 
weeks until 
suspected 
PD after CR 
or sCR. 
 
12. PK samples to be taken for belantamab mafodotin measurement C1D4 and C3D4 (±1 day)  
13. One PK sample to be taken for belantamab mafodotin measurement in Cycle 1 and Cycle 3 
on any day from Day 8 to Day 15. If dosing is delayed at Cycle 2 or Cycle 4, a PK sample 
should be drawn 21 days post dose (Day 22 2 days) in Cycle 1 and Cycle 3.  
14. PK samples to be taken on Cycle 3, Day 1 at the following study times: predose (within 30 
minutes prior to SOI), at EOI (5 min), at 2 h (±15 min) after SOI, and at 24 h (±2 hrs) after 
SOI. At C2, C4, C6, C9, and C12, PK samples to be taken at predose (within 30 minutes 
prior to SOI) and at EOI (5 min). Every 6 subsequent cycles (e.g., C18, C24, etc.) at 
predose (within 30 minutes prior to SOI). 
15. Anti-drug antibodies should be collected prior to the dose at C2, C6, C9, C12, and every 6 
cycles thereafter (C18, C24, etc.) until end of treatment (dosing days only) with the PK 
sample 
16. Response assessment must be conducted every 3 weeks based on disease laboratory tests 
and imaging (if applicable) as outlined in this table. Response evaluation will be performed 
according to the IMWG (Uniform Response Criteria for Multiple Myeloma 2016). Central 
laboratory results for all disease response assessments will be shared with the Independent 
Review Committee (IRC) 
17. Only if clinically indicated or if worsening clinical symptoms suggest skeletal PD.  
18. Imaging is only required for participants with extramedullary disease (CT, MRI, or PET/CT 
can be applied per local guidance). The same modality should be used throughout the study 
(i.e., if CT scan was used as baseline, participant needs to be followed by CT scans). 
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 skin only involvement, 
skin lesions should be measured with a ruler. Measurement of tumor size will be determined 
by the Sum of the Products of the maximal perpendicular diameters of measured lesions 
SPEP (Serum 
Protein 
Electrophoresis) 
 
 
 
X 
 
Serum 
Immunofixation 
 
 
 
By central 
lab if SPEP 
is negative 
at the time of 
first 
achieving 
CR then 
perform 
every 3 
weeks until 
suspected 
PD after CR 
or sCR. 
 

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Study 
Assessments 
Cycle 1, 
Day 11  
Cycle 1 
& 
Cycle 3 
Day 4 
Cycle 1 
&  
Cycle 3, 
Day 8-15
Q3W 
starting 
Wk 42 (to be 
performed 
regardless 
of dosing) 
Cycle 2-
CX with 
dosing 2 
Notes 
Serum Kappa, 
Lambda free Light 
chain, FLC ratio 
 
 
 
X 
 
(SPD). Digital copies of all scans must be maintained at the investigator site as source 
document. For sites in Germany: Only MRI is allowed to be used as imaging modality for 
participants with extramedullary disease.  
19. Germany: no PET/CT to confirm CR or sCR will be performed until approval by the German 
Federal Office for Radiation Protection until further notice. 
20. Only required for participants with IgD/E myeloma, where serum m-component cannot be 
followed otherwise 
21. Minimal residual disease (MRD) to be performed by the central lab at the time of first 
achieving VGPR or CR, repeat MRD testing 6 mo and 12 mo after achieving VGPR or CR 
(provided VGPR/CR is maintained). If MRD sample is drawn after date of achieving VGPR or 
CR the repeat testing should take place 6 months and 12 months from the time of initial MRD 
testing.  
22. In participants achieving a CR, bone marrow biopsy to confirm sCR by IHC.  
23. sBCMA samples to be taken in all participants for belantamab mafodotin measurement 
during Cycle 1, Day 1 and Cycle 3, Day 1 at the following study times: predose (within 30 
minutes prior to SOI), at EOI (5 min), at 2 h (±15 min) after SOI, and at 24 h (±2 hrs) after 
SOI, on Cycle 1 Day 4 (1 days) and one sample at any time between Cycle 1 Day 8 & Day 
15, with the PK samples. Pre-infusion sBCMA samples are collected prior to belantamab 
mafodotin infusion during each of the first 18 cycles: after which, sBCMA sample should be 
collected every 3 cycles, i.e. pre-infusion C18D1, C21D1, C24D1, etc.  
24. Upon PD- Optional tumor sample (BM aspirate clot, or fresh tissue, or tissue block from 
extramedullary tumor) for BCMA expression analysis by IHC. To be submitted to central lab 
for analysis.  
25. Belantamab mafodotin administration: Study drug administration 3-day window. In case a 
dose is delayed, the participant should wait for the next scheduled dose to resume treatment. 
Please refer to Section 6.2.2 
Calcium corrected 
for albumin (serum) 
 
 
 
X 
 
IgG, IgM, IgA 
 
 
 
X 
 
IgD/E20 
 
 
 
X 
 
Bone Marrow (BM) Aspiration/Biopsy 
BM for MRD 
testing21 
 
 
 
X 
 
BM for disease 
assessment 
(aspirate, preferred)  
 
 
 
At the time 
of CR 
(always) or 
at time of 
suspected 
PD (only if 
not evident 
otherwise) 
 
Bone marrow 
biopsy to assess 
sCR by IHC22 
 
 
 
Only if CR 
have been 
achieved on 
this visit 
 
Biomarker 
Soluble BCMA 
(serum)5, 23 
X 
X 
X 
 
X 
cfDNA (plasma)  
X 
 
 
 
 
Optional  
Optional tissue 
sample at PD for 
BCMA24 
 
 
 
X 
 

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Study 
Assessments 
Cycle 1, 
Day 11  
Cycle 1 
& 
Cycle 3 
Day 4 
Cycle 1 
&  
Cycle 3, 
Day 8-15
Q3W 
starting 
Wk 42 (to be 
performed 
regardless 
of dosing) 
Cycle 2-
CX with 
dosing 2 
Notes 
Genetics sample 
(optional)  
 
 
X 
 
 
 
 
26. Corneal management information:  
 
a) Prophylactic preservative-free artificial tears must be administered in each eye at least 4-8 
times daily beginning on Cycle 1 Day 1 until end of treatment. 
b) At the start of each infusion, participants may apply cooling eye masks to their eyes for 
approximately 1 hour or as long as tolerated.  
b) Selected sites will participate in an ocular sub-study.  
27. NEI-VFQ-25 and OSDI will be administered every 3 weeks even if dose is delayed. 
Additional assessments may be conducted for those participants who are experiencing a 
worsening in visual function.  
28. EORTC- QLQ-C30 and EORTC QLQ-MY20 should start at week 7 and continue every 6 
weeks. 
29. Patient Interview (PRO) must be conducted via telephone within 21 days (7 days) following 
Day 1 of the fourth treatment cycle (C4D1). The second patient Interview must be completed 
within 21 days (7 days) of the participants end of treatment visit, unless the participant has 
already completed their interview following C4D1 within the prior 30 days 
 
Treatment 
Premedication if 
needed 
X 
 
 
 
X 
Belantamab 
mafodotin 
administration25 
X 
 
 
 
X 
Preservative-free 
artificial tears 26 
X 
 
 
X 
X 
Health Outcomes 
PRO-CTCAE 
X 
 
 
X 
 
NEI-VFQ-2527 
X 
 
 
X 
 
OSDI27 
X 
 
 
X 
 
EORTC QLQ-C3028 
X 
 
 
every 6 
weeks 
 
EORTC QLQ-
MY2028 
X 
 
 
every 6 
weeks 
 
Patient Interview 
(PRO) 29 
 
 
 
 
X 
(within 21 
days 
after C4 
Day 1) 
 

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ADA = Anti-drug Antibody; ALP = alkaline phosphatase BM = bone marrow; BP = blood pressure; C1D1 = Cycle 1 Day 1, etc.; cfDNA = Circulating free DNA; CK = creatine kinase; 
CRP = C-reactive protein; EM = extramedullary; EOI = End of Infusion; EORTC QLQ-C30 = European Organization for Research and Treatment of Cancer Quality of Life 
Questionnaire 30-item Core module; EORTC QLQ-MY20 = European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 20-item Multiple Myeloma 
module; FISH = fluorescence in situ hybridization; FLC = free light chain; ; HR= heart rate; Ig = immunoglobulin; KVA = Keratopathy Visual Acuity; NEI-VFQ-25 = National Eye Institute 
Visual Functioning Questionnaire 25; OSDI = Ocular Surface Disease Index; PRO-CTCAE = Patient Reported Outcome version of the Common Term Criteria for Adverse Events; PD = 
Progressive Disease; PK = Pharmacokinetics; QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis. 
 

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Table 3 
Schedule of Activities: End of Treatment (EOT) and Follow-Up Assessments 
Study Assessments 
EOT Visit1 
PFS 
Follow-up2 
OS 
Follow-
Up3 
Notes 
Physical Exam 
X 
X 
 
1. 
The EOT visit is to assess any residual AEs or toxicities associated with 
treatment. The visit should occur within 45 days after last dose or before 
the start of any new anti-cancer therapy.  
2. 
PFS follow-up every 21 days (±7 days) for participants who discontinue 
IP for a reason other than PD. Disease evaluations will continue until 
confirmed PD, death, start of a new anticancer treatment, withdrawal of 
consent, or end of the study whichever occurs first.  
3. 
Survival follow-up every 3 months (14-day window): After PD is 
documented, participants will be followed for survival and subsequent 
anticancer therapy by chart review, phone call, or any form of 
communication every 3 months. Record participant’s survival status and 
whether subsequent treatment for disease was given. Participant does 
not need to come in for visit unless they are being followed for corneal 
signs that are present at the end of study treatment.  
4. 
All related SAEs are to be collected from consent through OS follow-up. 
5. 
End of treatment ophthalmic exam to be performed by an 
ophthalmologist (or an optometrist if an ophthalmologist is not 
available). See Section 8.2.9 for the list of ophthalmic exam procedures. 
6. 
Participants with corneal events per the GSK/KVA Scale for treatment 
related corneal events present at the end of study will continue to be 
followed at 3 and 6 weeks after the EOT visit and then every 6 weeks (±7 
days) for up to 12 months, or until full resolution of ophthalmic changes or 
deemed clinically stable by ophthalmologist (an optometrist if an 
ophthalmologist is not available, whichever comes first. Clinically stable is 
defined as any GSK/KVA Grade 1 exam finding (mild keratopathy) and a 
one-line change in vision when compared to baseline or no exam findings 
Safety 
Adverse Events4 
X 
Related 
SAEs only 
Related 
SAEs 
only 
Concomitant 
Medications 
X 
X 
 
Ocular Exam 
X5 
X6 
X6 
ECOG Performance 
Status 
X 
 
 
Vital Signs (BP, HR, 
Body Temperature) 
X 
 
 
Weight and Height 
Weight only 
 
 
Hematology7 
X 
 
 
Clinical chemistry7 
X 
X 
 
Urine Dipstick7 
X 
X 
 
eGFR (by MDRD 
formula- see Appendix 
10) 
X 
 
 
Spot urine for 
albumin/creatinine ratio 
X 
 
 
CRP 
X 
 
 
Pregnancy Test 8 
X 
X 
 
 
 
 
 
Pharmacokinetics PK 
X 
 
 
Anti-drug antibodies 
X 
 
 
Disease Evaluation 
Response Assessment9 
X  
X 
 

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Study Assessments 
EOT Visit1 
PFS 
Follow-up2 
OS 
Follow-
Up3 
Notes 
Imaging for 
Extramedullary 
disease10 
X 11 
Every 12 weeks if clinically 
indicated 
 
and a one-line change in vision when compared to baseline or a 
GSK/KVA Grade 1 exam finding (mild keratopathy) and no change in 
vision since baseline. Once clinically stable the event will not be followed 
up further; therefore, no repeat exam necessary. Corneal exams to be 
performed by an ophthalmologist (an optometrist if an ophthalmologist is 
not available). See Section 8.2.9 for the list of ophthalmic exam 
procedures).  
7. 
Refer to Table 14 for a comprehensive list of lab tests that must be 
collected for all participants. Only serum creatinine is required at PFS 
visits (not a full chemistry) 
8. 
Perform only in women of child-bearing potential. For questionable cases 
of whether a participant is of non-childbearing potential, obtain follicle 
stimulating hormone (FSH) and estradiol. See Section 5.1, Section 8.2.8, 
and Appendix 5 for more details. 
Final pregnancy test (serum or urine) must be performed in women of 
childbearing potential at the EOT visit and 4 months after the last dose of 
study treatment (may be via a urine pregnancy kit mailed to the 
participant’s home with results reported by telephone).  
9. 
For participants who are discontinuing IP due to PD the confirmation 
based on laboratory parameters must be performed from a different 
blood collection within 14 days of the original disease progression, 
preferably before institution of any new anti-myeloma therapy. This may 
be performed at the EOT visit. For participants with PD due to 
extramedullary disease, confirmatory scans are not required. The 
laboratory parameters do not need to be repeated only if the 
extramedullary disease is the singular site of progression. 
10. Imaging is only required for participants with extramedullary disease (CT, 
MRI, or PET/CT can be applied per local guidance). The same modality 
PET/CT upon achieving 
CR or sCR12 
Once after CR or sCR 
declared 
Once after CR or sCR 
declared 
 
UPEP (Urine Protein 
Electrophoresis) 24 hr. 
urine collection 
X 
X 
 
Urine immunofixation 
(Central lab) 
By central lab if UPEP is 
negative, at the time of first 
achieving CR then perform 
every 21 days ( 7 days) 
until suspected PD after CR 
or sCR.  
By central if UPEP is 
negative, at the time of first 
achieving CR then perform 
every 21 days ( 7 days) 
until suspected PD after CR 
or sCR. 
 
SPEP (Serum Protein 
Electrophoresis) 
X 
X 
 
Serum Immunofixation 
By central lab if SPEP is 
negative, at the time of first 
achieving CR then perform 
every 21 days ( 7 days) 
until suspected PD after CR 
or sCR. 
By central lab if SPEP is 
negative, at the time of first 
achieving CR then perform 
every 21 days ( 7 days) 
until suspected PD after CR 
or sCR. 
 
Serum Kappa, lambda 
free LC, FLC ratio 
X 
X 
 
Calcium corrected for 
albumin (serum) 
X 
X 
 
IgG, IgM, IgA 
X 
X 
 
IgD/E13 
X 
X 
 
Bone Marrow (BM) Aspiration/Biopsy 
BM for MRD testing14 
 
X 
 

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Study Assessments 
EOT Visit1 
PFS 
Follow-up2 
OS 
Follow-
Up3 
Notes 
BM for disease 
assessment 
Only if CR has been 
achieved by this visit, or 
suspected PD not evident 
otherwise 
Only if CR has been 
achieved by this visit, or 
suspected PD not evident 
otherwise 
 
should be used throughout the study (i.e., if CT scan was used as 
baseline, participant needs to be followed by CT scans). 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 skin only involvement, skin lesions should be measured with a ruler. 
Measurement of tumor size will be determined by the Sum of the 
Products of the maximal perpendicular diameters of measured lesions 
(SPD). Digital copies of all scans must be maintained at the investigator 
site as source document.  
11. 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. 
12. Germany: no PET/CT to confirm CR or sCR will be performed until 
approved by the German Federal Office of Radiation Protection until 
further notice.  
13. Only required for participants with IgD/E myeloma, where serum m-
component cannot be followed otherwise. 
Bone marrow biopsy to 
assess sCR by IHC15 
Only if CR has been 
achieved on this visit 
Only if CR have been 
achieved on this visit 
 
Biomarkers 
Soluble BCMA (serum)  
X 
 
 
cfDNA (plasma) 
X  
 
 
Optional 
Optional tissue sample 
at PD for BCMA16 
At time of PD 
At time of PD 
 
Health Outcomes 
PRO-CTCAE 
X 
 
 
NEI-VFQ-25 
X 
X 
X17 
OSDI 
X 
X 
X17 
EORTC-QLQ-C30 
X 
 
 
EORTC-QLQ-MY20  
X 
 
 
Patient Interview (PRO) 
18 
X 
 
 
Survival Status phone 
call 
 
 
X 

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Study Assessments 
EOT Visit1 
PFS 
Follow-up2 
OS 
Follow-
Up3 
Notes 
Subsequent Treatment 
Information 
 
X 
X 
14. Performed by a central lab at the time of first achieving VGPR or CR. And 
repeated at 6 months and 12 months after achieving the VGPR or CR 
(provided VGPR/CR is maintained). If MRD sample is drawn after date of 
achieving VGPR or CR the repeat testing should take place 6 months 
and 12 months from initial MRD testing 
15. In participants achieving a CR, bone marrow biopsy to confirm sCR by 
IHC. 
16. Upon PD- Optional tumor sample (BM aspirate clot, or fresh tissue, or 
tissue block from extramedullary tumor) for BCMA expression analysis by 
IHC. To be submitted to central lab for analysis 
17. Participants who discontinue participation in the study will continue to be 
assessed during follow-up for up to 12 months from EOT, or until 
resolution of visual symptoms and/or resolution of ophthalmic changes to 
baseline or deemed clinically stable by ophthalmologist (an optometrist if 
an ophthalmologist is not available, whichever comes first. Continue to 
follow up with participants via telephone who are still experiencing visual 
symptoms even after discontinuation 
18. Patient Interview (PRO) must be conducted via telephone within 21 days 
(7 days) of the end of treatment visit, unless the participant has already 
completed their interview following C4D1 within the prior 30 days. 
 
Abbreviations: 
BM = bone marrow; BP = blood pressure; cfDNA = Circulating free DNA; CRP = C-reactive protein; EORTC QLQ-C30 = European Organization for Research and Treatment of Cancer 
Quality of Life Questionnaire 30-item Core module; EORTC QLQ-MY20 = European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 20-item Multiple 
Myeloma module; FISH = fluorescence in situ hybridization; FLC = free light chain; ; HR= heart rate; Ig = immunoglobulin; KVA = Keratopathy Visual Acuity; NEI-VFQ-25 = National 
Eye Institute Visual Functioning Questionnaire 25; OSDI = Ocular Surface Disease Index; PRO-CTCAE = Patient Reported Outcome version of the Common Term Criteria for Adverse 
Events; PD = Progressive Disease; PK = Pharmacokinetics; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis. 

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Table 4 
Ocular Sub-Study Schedule of Activities (Selected Sites Only) 
Study Assessments  
Screen  
Cycle 1-
Cycle 4  
C1-C4 
10 days 
post  
Dose 
exam 
Every 3 weeks starting at week 4 (to be completed 
regardless of dose given) 
C5-
CX 
End of 
Treatment 
PFS 
Follow-up  
OS Follow-
up  
Informed Consent 1 
X 
 
 
 
 
 
 
 
Steroid eye drops 2 
 
X 
 
 
X6 
 
 
 
Preservative-free 
artificial tears 3 
 
X3 
X3 
X3 
X3 
 
 
 
Full Ocular exams 1,4 
X 
X 
X 
X 
X6 
X 
X6 
X6 
Specialty Ocular Exams1, 
5, 6 
X 
X 
X 
X 
 
X 
 
 
 
1. 
Informed consent obtained for inclusion into the ocular sub-study population. Consent must be obtained prior to performing any sub-study protocol-related procedures. All 
Screening assessments must be performed within 21 days prior to first dose unless otherwise specified. There is no need to repeat screening ocular assessments at C1D1 if they 
have been done within 21 days of first dose.  
2. 
Steroid eye drops administered as prophylaxis (such as: prednisolone acetate 1.0%, prednisolone phosphate 1%, dexamethasone 0.1%, or equivalent) 1 drop QID starting 1 day 
prior to each belantamab mafodotin infusion and continuing for a total of 7 consecutive days. Steroid eye drops are to be administered in only one eye as assigned (randomized) 
centrally by the Sponsor and the site staff will instruct the participant which eye will be treated. The ophthalmologist will remain blinded to this decision. The treating 
ophthalmologist has discretion to begin steroid drops in the both eyes should the participant develop symptoms requiring intervention as clinically indicated. Intraocular pressure 
should be monitored if steroid eye drops are used for more than 7 consecutive days. ***Based on data from the primary analysis the use of prophylactic steroid eye drops is no 
longer required for main study participants. Determination for use of steroid eye drops will be up to the discretion of the treating ophthalmologist for the ocular sub-study 
participants.  
3. 
Prophylactic preservative-free artificial tears will be administered starting 1 day prior to C1D1 according to Section 8.2.10.1. Outside of the 7-day prophylaxis period they should be 
administered at least 4-8 times daily as needed, at least one drop in each eye, until end of treatment or as clinically indicated.  
4. 
Participants will undergo ‘full’ ocular exams as outlined in Section 8.2.9 within 3 days prior to day 1 and on day 10 (3 days) of Treatment Cycles 1, 2, 3 and 4 (4 doses of study 
medication). Day 10 exam is only necessary after participant receives study medication. 
5. 
Participants could undergo ’specialty’ ocular exams as outlined in Section 8.2.10 on Day 10 (3 days) of Treatment Cycles 1, 2, 3 and 4 (4 doses of study medication) and within 3 
days prior to day 1 of cycles 2,3, and 4. A Day 10 exam is only necessary if participant receives study medication. 
6. 
After Cycle 4 Day 10, participants who have no signs/symptoms should revert to the ocular activities of the general participant population (see main SOA tables), treatment with 
steroid eye drops, and specialty ocular exams should continue at the discretion of the treating ophthalmologist. If a participant subsequently develops ocular signs/symptoms, or 
they require additional treatment, participant must be evaluated by an ophthalmologist (an optometrist if an ophthalmologist is not available) and treated as clinically indicated.  

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2. 
INTRODUCTION 
Multiple myeloma (MM) is an incurable malignancy and accounts for 1% of all cancers 
and for 10% of all hematologic malignancies. Worldwide, approximately 103,000 new 
cases are diagnosed annually, and an estimated 30,330 new cases and 12,650 deaths will 
occur in the US in 2016 [Siegel, 2016]. There have been significant advances in treatment 
for MM, including novel therapies like second and third -generation proteasome 
inhibitors (PIs), immunomodulatory agents, and recent addition of monoclonal antibodies 
(mAbs). Those advances have contributed to incremental gains in PFS and OS, but most 
MM patients still relapse and ultimately develop resistance to existing therapies. 
Therefore, there is an urgent need to develop treatments with novel MOA which could 
potentially prevent the cross resistance to existing therapies [Kumar, 2004]. Details of the 
characteristics of belantamab mafodotin, nonclinical, and clinical activity are provided in 
the Investigator’s Brochure (IB) [GSK2857916 GlaxoSmithKline Document Number 
2013N175128_09, 2021].  
2.1. 
Study Rationale 
Before the introduction of daratumumab, patients with disease that is refractory to both 
immunomodulatory agents and proteasome inhibitors (PIs) had a median overall survival 
(OS) ranging from 9 months [Kumar, 2012] to 12 months [Kumar, 2004; Kumar, 2003].  
Daratumumab [DARZALEX, 2017], is a human IgGk monoclonal antibody that was 
granted accelerated approval as monotherapy for the treatment of RRMM in the US in 
November 2015 [Afifi, 2016] on the basis of the results from a Phase II monotherapy 
study (n=106) which reported 29.2% ORR and mPFS 3.7 months in patients with 
relapsed or refractory multiple myeloma. The median number of prior lines of treatment 
reported in this study was 5. 
Later, daratumumab has been approved in combination with 
lenalidomide/dexamethasone, bortezomib/dexamethasone for patients who were 
previously treated with at least one prior line, and in combination with pomalidomide and 
dexamethasone for patients previously treated with at least 2 prior lines [DARZALEX, 
2017; Janssen-Cilag International NV, 2016].  
While the data with daratumumab indicate that further prolongation of PFS can been 
achieved, it is also increasingly recognized that patients continue to relapse after 
treatment with daratumumab and will need additional treatment options to control the 
disease. Patients with MM who relapse after daratumumab therapy, have few treatment 
options available and could benefit from treatment with a novel drug such as belantamab 
mafodotin.  
Belantamab mafodotin is a first in class, ADCC enhanced, humanized immunoglobulin 
G1 (IgG1) antibody-drug conjugate (ADC) that binds specifically to B-cell maturation 
antigen (BCMA), a target present on mature B cells and on tumor cells in patients with 
MM [Tai, 2015; Tai, 2006]. The antibody is conjugated to the microtubule inhibitor 
monomethyl auristatin-F (MMAF) and is produced as an afucosylated form that 
generates an enhanced antibody-dependent cellular cytotoxicity (ADCC) response. As 

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demonstrated in the FTIH study this novel mechanism of action can be reasonably 
expected to overcome cross resistance to existing therapies.  
Belantamab mafodotin has shown strong single-agent activity in the currently ongoing 
FTIH study BMA117159.  
Among the 35 participants receiving belantamab mafodotin at the RP2D of 3.4 mg/kg IV, 
Q3W, the following results were observed:  
• Overall response rate (ORR) of 60% (95% CI: 42.1%, 76.1%)  
• Median progression-free survival (PFS) was 7.9 months (95% CI: 3.1, - 
months).  
• The ORR in 14 participants who failed prior daratumumab treatment was 
43% (95% CI: 17.7%, 71.1%), and the PFS in this subgroup was 6.8 mo.  
• Overall, belantamab mafodotin was well tolerated and adverse events were 
manageable.  
This data supports further development of belantamab mafodotin as monotherapy in 
patients who failed an anti-CD38 antibody and are refractory to PI and 
immunomodulatory agent. 
2.2. 
Background – BCMA and Multiple Myeloma 
B-cell maturation antigen (BCMA also referred to as TNFRSF17 or CD269) is a member 
of the tumor necrosis factor (TNF) receptor superfamily and regulates a variety of 
cellular functions. BCMA is expressed in mature B lymphocytes and binds to two TNF 
family ligands BAFF (B-cell-activating factor belonging to the TNF family) and APRIL 
(a proliferation-inducing ligand) which promotes B-cell survival and proliferation. Mice 
deficient for BCMA are viable, have normal B-cell development, and exhibit normal 
humoral responses [Belnoue, 2008; Varfolomeev, 2004; Jiang, 2011]. BCMA is 
expressed on malignant plasma cells in all MM patients [Tai, 2015; Tai, 2006]. The 
restricted expression profile of BCMA in normal tissue, combined with its up-regulation 
and recognized survival function in MM [Tai, 2006; Sanchez, 2012; Novak, 2004] makes 
BCMA an attractive target for a therapeutic antibody with direct cell killing activity and 
with minimal off target effects [Tai, 2015]. BCMA has been validated as a therapeutic 
target in MM [Tai, 2015]. The BMA117159 study was the first time in human (FTIH) 
study demonstrating single-agent activity of belantamab mafodotin in heavily pre-treated 
MM participants. Chimeric Antigen Receptor T-Cells (CAR-T) based therapies targeting 
BCMA have also demonstrated powerful activity against MM, with substantial albeit 
reversible risks [Cohen, 2016]. Other approaches utilizing bispecific antibodies (BiTe) 
have also entered development, but clinical results have not been reported at the time of 
writing this protocol.  
2.3. 
Antibody-Drug Conjugate Belantamab Mafodotin 
Belantamab mafodotin is a first in class, ADCC-enhanced, humanized immunoglobulin 
G1 (IgG1) antibody drug conjugate (ADC) that binds specifically to B-cell maturation 
antigen (BCMA), a target restricted to B cells at later stages of differentiation and 
expressed on tumor cells of all patients with MM [Tai, 2015; Tai, 2006]. The antibody 

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moiety of belantamab mafodotin is produced as an afucosylated form that generates an 
enhanced antibody-dependent cellular cytotoxicity (ADCC) response upon binding to 
FcRIIIa receptors on the surface of human immune effector cells. The antibody is 
conjugated to the microtubule inhibitor monomethyl auristatin-F (MMAF).  
Upon binding to the cell surface, belantamab mafodotin is rapidly internalized and the 
active drug (cys-mcMMAF) is released inside the cell. The cys-mcMMAF moiety 
disrupts microtubule networks, leading to cell cycle arrest and apoptosis (ADC 
mechanism) [Alley, 2009; Pettit, 1998]. This dual mechanism of action of belantamab 
mafodotin (ADCC and microtubule disruption) enables anti-tumor activity on both 
dividing and non-dividing cells. In addition, when MM cell lines expressing BCMA are 
exposed to belantamab mafodotin, it may act as an inducer of immunogenic cell death 
(ICD) [Kroemer, 2013; Krysko, 2012], representing a potential third mechanism of 
action. Exposure of dendritic cells to tumor cells undergoing ICD induces an antigen-
specific T-cell response, and if it acts similarly in humans could induce the patient’s own 
immune response against the MM tumor. Expression of the target of belantamab 
mafodotin (BCMA) is restricted to B cells at later stages of differentiation. The target is 
also present on tumor cells of all patients with MM [Tai, 2015; Tai, 2006]. 
2.4. 
Human 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 [GSK2857916 GlaxoSmithKline Document Number 
2013N175128_09, 2021; Trudel, 2019].  
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 immunomodulatory agents 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].  

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Phase II study 205678/DREAMM-2 
The ongoing Phase II study 205678/DREAMM-2 is evaluating these two IV single agent 
doses (2.5 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 immunomodulatory agent and a proteasome 
inhibitor. A total of 194 participants received frozen drug product in the main cohort and 
24 participants received 3.4 mg/kg lyophilized drug product. Primary analysis data from 
this study indicated no new safety signals, and the profile of adverse events was similar to 
the experience in the DREAMM-1 study for both arms. Both dose levels, 2.5 and 3.4 
mg/kg, were shown to have a positive benefit/risk profile [Li, 2017; Lonial, 2020].  
As of the cut-off date of 31 January 2020, the study met its primary endpoint for ORR in 
both the 2.5 mg/kg [ORR 31% (97.5% CI 21.7, 43.6)] and 3.4 mg/kg [ORR 35% 
(97.5%CI 24.8, 47.0)] frozen treatments, and the benefit of belantamab mafodotin was 
supported by the secondary endpoints. The median DoR was 11.0 months (95% CI: 4.2, 
NR) at 2.5 mg/kg and 6.2 months (95% CI: 4.8, NR) at 3.4 mg/kg. The mPFS in this 
population was 2.8 months (95% CI: 1.6, 3.6) and 3.9 months (95% CI: 2.0, 5.8), 
respectively and the median Overall Survival (mOS) was 13.7 months (95% CI: 9.9, NR) 
at 2.5 mg/kg and 13.8 months (95% CI: 10.0, NR) at 3.4 mg/kg. Positive clinical activity 
was also demonstrated at the 3.4 mg/kg lyophilised dose [ORR 52% (97.5% CI 28.9, 
74.5)].  
 
Safety 
Single-agent belantamab mafodotin was demonstrated to have a manageable safety 
profile in heavily pre-treated participants with RRMM. Safety data for single-agent 
belantamab mafodotin were pooled (data as of 20 September 2019) for DREAMM-2 
study and supportive FTIH study DREAMM-1 by treatment cohorts of 2.5 mg/kg and 
3.4 mg/kg. 
The most common AEs in both treatment cohorts were keratopathy (corneal epithelium 
changes observed on ophthalmic examination), thrombocytopenia and anemia. The 
incidence of AEs, including Grade 3/4 AEs was comparable between belantamab 
mafodotin 2.5 mg/kg and 3.4 mg/kg cohorts. Adverse events leading to dose delays, and 
reductions were less frequent in 2.5 mg/kg cohort, 51% and 32% compared with the 3.4 
mg/kg cohort, 67% and 52%, respectively. AEs leading to permanent treatment 
discontinuation occurred in 10% and 11% of participants in the 2.5 and 3.4 mg/kg 
cohorts, respectively. More participants in the 3.4 mg/kg cohort experienced SAEs (50%) 
and fatal SAEs (6%) compared with the 2.5 mg/kg cohort (41% and 3%, respectively). 
Single agent belantamab mafodotin 2.5 mg/kg was selected as the recommended dose 
based on comparable efficacy with a more favorable safety profile (i.e. lower incidence 
of thrombocytopenia and neutropenia and less frequent dose delays or reductions) 
compared with the 3.4 mg/kg dose. 
 

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2.4.1. 
Thrombocytopenia 
In DREAMM-2 (data cut off as of 31 January 2020), thrombocytopenic events 
(thrombocytopenia and platelet count decreased) occurred in 38% participants treated 
with belantamab mafodotin 2.5 mg/kg; severity ranging between Grade 1 and 4. The 
incidence of Grade 3 bleeding events was low (2%), with no Grade 4 or 5 events reported 
in participants treated with belantamab mafodotin 2.5 mg/kg. 
Most participants had a decrease from baseline in their platelet counts during the study. 
In general, participants who initiated treatment with lower platelet numbers tended to 
continue to have thrombocytopenia while on treatment with belantamab mafodotin. 
2.4.2. 
Corneal Events  
Corneal events, reported in most cases as keratopathy, blurred vision and dry eye events 
are the most frequently reported AEs with belantamab mafodotin. 
In DREAMM-2 (data cut off as of 31 January 2020), events in the Eye disorders SOC 
occurred in 78% of participants treated with belantamab mafodotin 2.5 mg/kg. The most 
common ocular AEs were keratopathy (71%, changes in corneal epithelium identified on 
eye exam, with or without symptoms), blurred vision (22%), and dry eye (13%). 
Decreased vision defined as Snellen score worse than 20/50 in the better seeing eye was 
reported in 18% of participants receiving belantamab mafodotin 2.5mg/kg. Severe vision 
loss defined as 20/200 or worse in the better seeing eye was reported in 1% of 
participants receiving belantamab mafodotin 2.5 mg/kg. 
The median time to onset of Grade 2 or above corneal findings (best corrected visual 
acuity (BCVA) or corneal examination) was 36 days (range: 19 to 143 days) in 
participants receiving belantamab mafodotin 2.5 mg/kg. The median time to resolution of 
these corneal findings was 91 days (range: 21 to 201 days). 
Participants with history of dry eye were more prone to develop corneal examination 
findings. Therefore, active management of dry eye symptoms prior to and during 
treatment is recommended (i.e. administration of preservative-free artificial tears). 
The ocular sub-study of DREAMM-2 provided no evidence that corticosteroid eye drops 
are beneficial in preventing or mitigating corneal events. 
2.4.3. 
Infusion-related reactions 
Infusion-related reactions (IRRs) are expected for biologic agents. In DREAMM-2 (data 
as of 31 January 2020), IRRs occurred in 21% of participants in the belantamab 
mafodotin 2.5 mg/kg, which were Grade 1 - 3 in severity. Most IRRs occurred with the 
first infusion and few participants experienced IRRs with subsequent infusions. 
Although not protocol-mandated, pre-medications for IRR prophylaxis (including 
paracetamol, antihistamines, and steroids) were administered to 26%–27% of 
participants. One participant (2.5 mg/kg cohort) discontinued treatment due to IRRs 
(Grade 3 IRRs at first and second infusion). 

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2.4.4. 
Pharmacokinetics and Pharmacodynamics 
The pharmacokinetics and pharmacodynamics of belantamab mafodotin (antibody-drug 
conjugate, including complex with soluble BCMA (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, 
two-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 
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.  

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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 seven days after 
dosing, reflecting binding of belantamab mafodotin to sBCMA. Maximum decreases 
ranged from 2% to 97%, which were qualitatively dose-dependent, with larger reductions 
in free sBCMA at higher doses.  
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 clinical PK, PD, and exposure-response 
relationships can be found in the Investigator’s Brochure [GSK2857916 IB, 
GlaxoSmithKline Document Number 2013N175128_09, 2021] 
2.5. 
Benefit / Risk Assessment 
2.5.1. 
Risk Assessment 
Additional information about the known and expected benefits and risks, detailed 
information of nonclinical and clinical findings information regarding warnings, 
precautions, contraindications, adverse events, and other pertinent information on 
belantamab mafodotin that may impact participant eligibility is provided in the 
Investigator’s Brochure [GSK2857916 (IB) GlaxoSmithKline Document Number 
2013N175128_09, 2021]. 
Table 5 
Risk Assessment and Mitigation Strategy 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Investigational Product (Belantamab Mafodotin) 
Corneal events  
Reversible corneal events have been 
observed with various ADCs (specific 
corneal changes with ADCs conjugated to 
MMAF). 
Cornea-related AEs such as blurred vision, 
dry/watery eyes, decreased visual acuity, 
and photophobia are among the most 
common AEs associated with belantamab 
mafodotin in the clinic. Corneal erosions 
and corneal ulcers (associated with 
infective keratitis) have also been reported. 
Active monitoring for corneal events 
according to the Schedule of Activities 
(Table 1).  
 
 
Timely evaluation and management by 
an ophthalmologist (an optometrist if an 
ophthalmologist is not available) upon 
developing corneal related events. 
Recommendations for dose 

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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
The majority of events have been non-
serious and transient, some requiring dose 
delays/reductions. Time to recovery is 
variable, and in some instances the 
resolution may take weeks to months.  
delays/reductions are provided in Section 
6.2.2 and Appendix 9.  
Infusion related 
reaction 
Without pre-medication, the majority of 
IRRs observed in the clinic to date have 
been G1-2 and non-serious; however, 
there have also been serious IRRs. 
Overall, participants who experienced an 
IRR during the initial infusion were pre-
medicated prior to subsequent infusions 
and IRRs did not recur. 
Participants will be closely monitored for 
signs of IRR.  
Premedication prior to first infusion of 
belantamab mafodotin is not mandatory 
but may be considered based on 
investigator judgment. 
If an infusion-related reaction occurs 
during belantamab mafodotin 
administration, the infusion rate may be 
reduced or halted depending on the 
severity of the symptoms. The participant 
will receive appropriate medical 
treatment. When the participant’s 
condition is stable, the infusion may be 
restarted. Upon restart, the infusion rate 
must be half of the infusion rate at the 
time the infusion was paused. 
Thrombocytopenia 
Thrombocytopenic events of all grades (1-
4) are among the most common AEs 
associated with belantamab mafodotin in 
the clinic.  
 
A hematologic panel is assessed 
frequently. Supportive therapy (including 
transfusions) is provided according to 
standard medical practice, and dose 
reductions or treatment discontinuations 
are outlined in Section 6.2. 
Neutropenia 
Non-serious and serious neutropenia has 
been observed in the clinic with 
belantamab mafodotin.  
A hematologic panel is assessed 
frequently. Supportive therapy (growth 
factors, antibiotics, and treatment of 
active infections) is provided according to 
standard medical practice, and dose 
reductions or treatment discontinuations 
are outlined in Section 6.2. 

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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Potential for 
cardiotoxicity related 
to an inflammatory 
response 
Preclinical inflammatory findings were 
seen in the rat mandibular and mesenteric 
lymph nodes, brachial/sciatic nerves, 
epididymides, lung, thymus, and atrial 
epicardium. In the monkey, microscopic 
effects in spleen and bone marrow at ≥3 
mg/kg/week were reflective of a systemic 
inflammatory response. 
Electrocardiograms (ECG) were monitored 
in monkeys for up to 24 hours following 
repeat dosing and did not produce any 
evidence of test-article induced 
electrocardiographic waveform 
abnormalities, arrhythmias or QTc 
changes. Serum cardiac troponin I was 
also measured in the rat and monkey 3-
week studies and no treatment-related 
effects were observed.  
This potential risk was based on described 
preclinical findings, however to date there 
is no evidence of systemic inflammatory 
response or cardiotoxicity in the clinic.  
Monitoring of ECG. Treatment as 
medically indicated. Monitoring of other 
cardiac parameters as clinically indicated. 
Laboratory 
abnormalities 
Report of non-serious, asymptomatic 
elevations in LDH / CK levels have been 
observed in the clinic. 
Monitoring of LDH and CK levels will be 
performed. 
Hepatotoxicity 
Non-clinical safety experiments 
demonstrated increased liver weight and 
elevated at doses of ≥10 mg/kg in rats. 
Elevations in liver enzymes, and increased 
mitotic figures in Kupffer cells were 
observed in monkeys ≥3 mg/kg. These 
changes were associated with minimal 
hepatocellular necrosis with cellular 
infiltrates which were reversible.  
Extramedullary hematopoiesis was 
observed in livers of monkeys and rats 
given ≥10 mg/kg. 
 
Non-serious elevations in alanine 
aminotransferase (ALT), aspartate 
aminotransferase (AST) have been 
observed in the clinical trials.  
Only participants with well-preserved liver 
function per the inclusion/exclusion 
criteria will be enrolled. Participants with 
chronic Hepatitis B (HBV) and C will be 
excluded from the trial. Liver function 
tests will be monitored. In case of liver 
abnormalities, management will be 
implemented according to clinical 
practice. Participants that meet liver 
stopping criteria (Section 7.2.1) will be 
withdrawn from the study. 
Potential for Other 
Laboratory 
Abnormalities 
Increased skeletal troponin I was observed 
in the single dose monkey study and 
increased skeletal troponin I and/or 
creatine kinase and aldolase in the rat 
studies. 
Cases of elevated aspartate 
aminotransferase (AST), lactic 
dehydrogenase (LDH) and creatine kinase 
(CK) alone or concomitant with no clear 
Monitoring of laboratory values will be 
continued as outlined in the protocol. In 
case of elevations of ≥ x3 ULN, 
participants should (where possible) have 
a sample sent for central testing of LDH 
and CPK isoenzyme levels. 

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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
clinical correlate have been observed in 
clinical studies. 
Participants with contemporaneous 
constitutional symptoms should be 
discussed with the Medical Monitor. 
Nephrotoxicity 
Non-clinical safety experiments have 
demonstrated primary glomerular injury 
and tubular degeneration (in rat and 
monkey). The morphologic changes were 
accompanied by large molecular 
proteinuria (albuminuria). The renal 
changes were dose dependent and 
reversible.  
During the study, participants will be 
monitored for kidney function by 
assessing creatinine, estimated 
glomerular filtration rate (eGFR), 
electrolytes, and albumin / creatinine 
ratios (spot urine). Participants will be 
educated about the need of maintaining 
adequate urinary output. Management 
will be implemented according to clinical 
practice. Dose reductions and treatment 
stopping criteria will be applied according 
to Section 6.2 and Section 7.2 
Pulmonary toxicity 
(pneumonitis) 
Preliminary nonclinical safety experiments 
have demonstrated the presence of 
microscopic changes in the lungs 
(prominent alveolar macrophages 
associated with flocculent eosinophilic 
material; mixed perivascular inflammation) 
in rats at all doses tested. To date no 
pneumonitis has been observed in the 
clinic. 
Monitoring for clinical signs and 
symptoms potentially related to 
pulmonary toxicity. Further diagnostic 
tests and management will be 
implemented immediately according to 
recommendations provided in Section 
6.2.2. 
Immunosuppression 
In nonclinical studies belantamab 
mafodotin has been associated with 
decrease in immunoglobulins in monkeys. 
An increase in immunoglobulins was seen 
in rats (rats are not an antigen specific 
species for belantamab mafodotin). 
Participants will be monitored for 
infections. Participants will receive 
immediate treatment according to 
standard practice. 
Potential for overdose 
specific to the 
preparation of study 
drug 
A frozen liquid configuration of belantamab 
mafodotin will be used to initiate this trial. 
An independent cohort of approximately 25 
additional participants will be enrolled and 
administered a lyophilized configuration of 
compound (upon availability). A separate 
set of preparation instructions will need to 
be followed in order to prevent potential 
overdose.  
Proactive communication and training will 
be provided to the sites ahead and at the 
time that the lyophilized configuration is 
introduced at the site. 
There is no specific antidote for overdose 
with belantamab mafodotin. In the event 
of a suspected overdose, it is 
recommended that the appropriate 
supportive clinical care should be 
instituted, as dictated by the participant’s 
clinical status. 
Embryo-Fetal Toxicity 
Nonclinical reproductive studies with 
belantamab mafodotin have not been 
conducted. Embryo-fetal toxicity is 
expected due to the cytotoxic component, 
cys-mcMMAF via nonspecific uptake 
and/or BCMA-mediated toxicity (due to 
reports of BCMA expression in human 
placental cells [Langat, 2008]). 
Use of belantamab mafodotin in pregnant 
women may cause fetal harm. 
See contraception requirements in 
Section 11.5 

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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
 
Impaired Male Fertility 
In animal studies, belantamab 
mafodotin treatment has resulted in 
testicular toxicity and adverse effects on 
spermatogenesis. Reversibility of testicular 
toxicity is unknown at this time. 
Men will be advised to have sperm 
samples frozen and stored before 
treatment. 
See contraception requirements in 
Section 11.5 
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 image 
acquisition: 
During the acquisition of imaging data 
(e.g., MRI, CT, PET, ECHO), non-MM 
disease or drug related clinically relevant 
abnormalities could be found by the 
radiographer or echocardiographer 
performing the exams. 
Copies of all medical images that include 
non-disease, clinically relevant 
abnormalities will be shared with the site 
for storage 
TCR = T-cell receptor; mAb = Monoclonal antibody; AEs = Adverse Events 
2.5.2. 
Benefit Assessment 
Belantamab mafodotin has demonstrated strong single-agent activity in 2 clinical studies 
conducted in heavily pre-treated participants with RRMM (Q3W schedule via IV 
administration). Based on the available data for the FTIH study BMA117159, as of the 
efficacy cut-off of 31 August 2018, participants receiving belantamab mafodotin at 
3.4 mg/kg had an ORR of 60% (95% CI: 42.1, 76.1) and a median PFS of 12.0 (95% CI: 
3.1, NR) in a heavily pre-treated population (57% ≥5 prior lines of therapy) [Trudel, 
2019; Trudel, 2018]. For participants refractory to both immunomodulators and 
proteasome inhibitors (N=32), the confirmed overall response rate was 56% (95% CI: 
37.7%, 73.6%). In 205678/ DREAMM 2, both dose levels evaluated, 2.5 and 3.4 mg/kg, 
had a positive benefit/risk profile [Li, 2017; Lonial, 2020].  
Based on this profile, it is reasonable to hypothesize that the use of belantamab mafodotin 
as a single agent will provide an improved benefit compared to the combination regimen 
of pom/dex in this patient population. 
2.5.3. 
Overall Benefit-Risk Conclusions 
Taking into account the measures to minimize risks to participants in this study, the 
potential risks identified in association with belantamab mafodotin are justified by the 
anticipated benefits that may be afforded to participants with RRMM. 
3. 
OBJECTIVES AND ENDPOINTS 
The purpose of this Phase II study is to evaluate the safety and efficacy of belantamab 
mafodotin in participants with RRMM who have received at least 3 prior lines of anti-
myeloma therapy, have failed an anti-CD38 antibody, and are refractory to PI and 

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immunomodulatory agents. See Table 6 for the primary, secondary, exploratory, and 
other objectives, along with the corresponding endpoints.  
Table 6 
Objectives and Endpoints for Study 205678 - Belantamab Mafodotin 
in RRMM Participants Previously Treated with an Anti-CD38 
Antibody 
Objectives 
Endpoints 
Primary Objective 
To evaluate the clinical efficacy of 2 doses 
of belantamab mafodotin in participants 
with relapsed/refractory multiple myeloma.  
ORR, defined as the percentage of participants with a confirmed 
partial response (PR) or better (i.e., PR, very good partial response 
[VGPR], complete response [CR] and stringent complete response 
[sCR]), according to the 2016 International Myeloma Working Group 
(IMWG) Response Criteria by Independent Review Committee (IRC). 
Secondary Objectives 
To further evaluate the clinical measures of 
efficacy of belantamab mafodotin in 
participants with RRMM 
 
 
ORR, defined as the percentage of participants with a confirmed 
partial response (PR) or better, according to the 2016 International 
Myeloma Working Group (IMWG) Response Criteria by investigator 
assessment. 
 
Clinical benefit rate (CBR), defined as the percentage of participants 
with a confirmed minimal response (MR) or better according to the 
2016 International Myeloma Working Group (IMWG) Response 
Criteria). 
 
Duration of response (DoR), defined as: the time from first 
documented evidence of PR or better until the earliest date of 
documented disease progression (PD) per IMWG; or death due to 
PD occurs among participants who achieve an overall response, i.e., 
confirmed PR or better. 
 
Time to response, defined as the time between the date of 
randomization and the first documented evidence of response (PR or 
better). 
 
Progression-free survival, defined as the time from randomization 
until the earliest date of documented disease progression (PD) per 
IMWG, or death due to any cause. 
 
Time to progression, defined as the time from randomization until the 
earliest date of documented PD per IMWG, or death due to PD. 
 
Overall survival, defined as the time from randomization until death 
due to any cause. 
To evaluate the safety of belantamab 
mafodotin in participants with RRMM. 
The safety profile of belantamab mafodotin will be evaluated in 
participants with RRMM as assessed through: 
standard clinical and laboratory tests (hematology and chemistry, 
physical examination, vital sign measurements, and diagnostic tests) 
through the collection of adverse events (AEs) and serious adverse 
events (SAEs) 
AEs of special interest 
ocular findings on ophthalmic exam 
To evaluate the pharmacokinetic profile of 
belantamab mafodotin 
Plasma concentrations of belantamab mafodotin (ADC, total mAb, 
and cys-mcMMAF) 
Derived pharmacokinetic parameter values (e.g., AUC, Cmax, tmax, 
t½), as data permit. 

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Objectives 
Endpoints 
To assess anti-drug antibodies (ADAs) 
against belantamab mafodotin 
Incidence and titers of ADAs against belantamab mafodotin 
Participant self-reported symptomatic 
adverse effects by evaluation of tolerability 
of belantamab mafodotin 
Symptomatic adverse effects and related impacts as measured by 
the PRO-CTCAE, NEI-VFQ-25 and OSDI 
To evaluate disease and treatment related 
symptoms and impact on function and 
health-related quality-of-life 
Health-related quality-of-life as measured by the EORTC QLQ-C30 
and EORTC QLQ-MY20 
Exploratory Objectives 
To explore the relationship between clinical 
response and other biologic characteristics 
including BCMA expression on tumor cells 
and sBCMA concentrations  
Determine BCMA expression levels and other markers on malignant 
cells, serum sBCMA levels, and evaluate the relationship of these 
factors to clinical response 
To investigate the relationship between 
genetic variants in the host and response 
to belantamab mafodotin  
Possible relationship between host genetic variation and response to 
belantamab mafodotin 
To evaluate disease and treatment related 
symptoms and impact on function and 
health-related quality-of-life 
Qualitative telephone interview(s) 
To explore exposure-response 
relationships between belantamab 
mafodotin exposure and clinical endpoints 
Explore relationships between belantamab mafodotin exposure (e.g., 
dose, dose intensity, concentration, Cmax, or AUC) and clinical 
endpoints (e.g., response, corneal event), if data permit 
To assess Minimal Residual Disease 
(MRD) in participants who achieve ≥VGPR 
or better 
Minimal Residual Disease (MRD) negativity rate, defined as: the 
percentage of participants who are MRD negative by Next 
Generation Sequencing (NGS). 
To assess the safety, efficacy, 
immunogenicity, and pharmacokinetics of 
belantamab mafodotin in a lyophilized 
configuration (approximately 25 
participants) 
AEs, clinical and laboratory assessments; descriptive analyses of 
ORR, duration of response, time to response, time to progression, 
overall response; incidence and titers against belantamab mafodotin; 
plasma concentrations of belantamab mafodotin (ADC, total mAb, 
and cys-mcMMAF) and derived pharmacokinetic parameters, if data 
permit 
Ocular sub-study objective 
To evaluate the effect of topical 
corticosteroids on corneal findings in 
approximately 30 participants who will 
receive monocular topical corticosteroids 
for the first 4 cycles 
Description of differences in corneal findings in each eye based on 
ophthalmic examinations (participant-level). 
Abbreviations: IV = intravenous; Q3W: once every 3 weeks; RRMM = relapsed refractory multiple myeloma; BCMA = 
B-cell maturation antigen; MMAF = monomethyl auristatin-F; MRD = minimal residual disease; NGS = Next Generation 
Sequencing; ORR = overall response rate; CI = confidence interval; CR = complete response; VGPR = very good 
partial response; PR = partial response; PFS = progression free survival; AUC = area under the curve; Cmax = 
maximum concentration; tmax = time to maximum; t½ = half-life; PRO-CTCAE = Patient Reported Outcomes-Common 
Terminology Criteria for Adverse Events; NEI-VFQ-25 = National Eye Institute Visual Functioning Questionnaire 25; 
OSDI = Ocular Surface Disease Index; EORTC = European Organisation for Research and Treatment of Cancer; 
QLQ-C30 = Quality of Life Questionnaire 30-item Core module; FLC = free light chain; SCT = stem cell transplant; 
QLQ-MY20 = ; Quality of Life Questionnaire 20-item module for MM; QTcF = QT interval corrected by Fridericia's 
formula; HIV = human immune deficiency virus; RNA = ribose nucleic acid. 
 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase II, open-label, two-arm, randomized, multicenter study to evaluate the 
efficacy and safety of belantamab mafodotin monotherapy at the dose of 2.5 mg/kg or 3.4 

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mg/kg IV, Q3W, in participants with RRMM. Participants will be treated until disease 
progression or unacceptable toxicity and will be followed for PFS and OS. An ocular 
sub-study will evaluate the effectiveness of steroid eye drops in approximately 30 
participants (~15 on each dose arm) who sign an optional ICF.  
The study will use frozen solution of belantamab mafodotin for those participants 
enrolled into 2 dose arms.  
The design includes an independent cohort of approximately 25 participants who will 
receive a lyophilized configuration of belantamab mafodotin. Those participants will 
follow the same assessments and procedures as the main study and will be analyzed 
separately from participants randomized to the frozen solution.  
The lyophilized cohort will be initiated when the lyophilized configuration becomes 
available. It will evaluate the 3.4 mg/kg dose level, unless the results of the IA indicate 
that it should not be continued. In that case, the lyophilized cohort will have a dose of 2.5 
mg/kg. 
The study consists of a screening/baseline period, a treatment period, and a post-
treatment follow-up period (schematic is displayed in Figure 1) 

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Figure 1 
Study 205678 Schematic 
 
 
Abbreviations: OS = overall survival; PD = progressive disease; PFS = progression-free 
survival; F/U = follow-up; lyo = lyophilized; DP = drug product; pts = participants. 
 
 

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Participants eligible for screening will be assigned a unique Participant Number by their 
investigational site. Upon completion of all the required screening assessments, eligible 
participants will be registered into the Registration and Medication Ordering System 
(RAMOS), GSK’s Interactive Response Technology (IRT) system, by the investigator or 
authorized site staff. Following randomization, eligible participants will begin Cycle 1 
treatment in the assigned treatment arm. Assessments will be performed as illustrated in 
the Schedule of Activities (Section 1.2).  
Selected investigative sites will participate in the ocular sub-study and will conduct 
additional ocular examinations on approximately 30 participants who sign an additional 
consent to receive monocular treatment with corticosteroid eye drops. In this specific 
subgroup, the ophthalmic examinations will occur pre-dose every 3 weeks and on Day 10 
after a treatment dose for the first 4 cycles. Additional treatments and examinations will 
be at the discretion of the treating ophthalmologist (an optometrist if an ophthalmologist 
is not available). See the SOA for the scheduling (Section 1.2).  
Additional details of the individual assessments are provided in Section 8. 
An interim analysis (IA) for futility is planned for ORR based on investigator’s 
assessment after approximately 25 participants per arm are evaluable for response 
(defined as having received at least 2 doses of study treatment and having completed at 
least 1 disease assessment after the second dose, or progressed or died or discontinued 
treatment due to reasons other than PD).  
At the IA, given that 25 participants are evaluable for each arm, treatment arm/s will be 
dropped from the study if there are ≤4 responses. If both arms have 5 or more responses 
at IA, in addition to the futility rule described above, the posterior probability of 
observing a better RR in one arm than the other will be calculated. If such a probability is 
at least 97.5%, then the treatment arm with lower RR will be dropped due to lack of 
efficacy.  
The IA to assess futility will be performed by an Independent Data Monitoring 
Committee (IDMC). Additional details of the IA are provided in Section 9.5.9 and will be 
provided in an IDMC Charter. At the time of the IA, additional participants will continue 
to be enrolled, treated, and followed as described in the SOA (Section 1.2). Efficacy and 
safety results from the interim analysis will not be shared with investigators or other 
site/study personnel. 
If one arm is selected based on the results of the IA, enrollment to the futile arm will be 
stopped and ongoing participants from the futile arm will have the possibility upon 
additional consent to either continue at their current dose level or to have their dose 
adjusted to the dose in the selected arm based on the following rules: 
If the 2.5 mg/kg dose is discontinued, participants have the option to switch to 
3.4 mg/kg dose if they: 
• 
Did not experience an SAE, or a ≥ Grade 3 non-corneal AE 
• 
Provide informed consent for the 3.4 mg/kg dose. 

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If the 3.4 mg/kg dose is discontinued, participants who are currently treated at this 
dose will have the option to switch to 2.5 mg/kg:  
• 
In cases when the participant has not achieved a maximum benefit of CR or sCR, did 
not experience toxicity requiring a dose reduction, and is willing to continue at the 
higher dose level, the participant will have the option to stay on their original dose 
upon signing an additional informed consent informing them that a lower dose level 
has been selected for the remaining participants.  
The final analysis of the primary endpoint (ORR) will be performed 6 months after the 
last participant is randomized. The study will continue and participants will remain on 
treatment and continue to be followed.  
For participants who discontinue study treatment for reasons other than PD, disease 
evaluations will continue to be performed at 3-week intervals until confirmed PD, death, 
start of a new anticancer treatment, withdrawal of consent, or end of the study whichever 
occurs first. After PD is documented, participants will be followed for survival and 
subsequent anticancer therapy every 3 months until study ends.  
Pharmacokinetic samples will be collected from all participants. The collection of PK 
samples for determination of belantamab mafodotin plasma (ADC and total antibody) 
and cys-mcMMAF concentrations will allow characterization of the PK profile and 
support investigation of its pharmacology. 
Genetic testing (in consenting participants) and biomarker research samples will also be 
conducted on samples from all participants prior to the first dose. Patient-Reported 
Outcomes (PRO) data will be collected at each clinic visit. 
Protocol waivers or exemptions are not allowed. Therefore, adherence to the study design 
requirements, including those specified in the SOA (Table 1 to Table 4) is essential. 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying Study Reference Manual (SRM). The SRM will provide 
the site personnel with administrative and detailed technical information that does not 
affect participant safety. 
Following 39 months post LSFD, the study will move into the PACT phase where the 
study remains open only to provide continued access to treatment for study participants 
who are continuing to derive clinical benefit. At that time, the collection of new data for 
participants who no longer receive study treatment will stop and the clinical trial database 
will be closed. Participants in survival follow-up will be considered to have completed 
the study. Those participants still benefiting from study drug in the opinion of their 
treating physician may continue to receive study drug and only SAEs, AEs leading to 
treatment discontinuation, overdose and pregnancy cases, and pre-specified ocular data 
will be reported directly to GSK using paper forms. The end of study (EOS) is defined as 
the date of the last visit of the last participant in the study.  
 

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4.2. 
Number of Participants 
Approximately 170 participants were initially planned to be screened to enroll a 
minimum of 155 participants at approximately 60 investigational sites globally. A 
minimum of 130 participants (65/arm) were planned to be enrolled to 2 arms receiving 
frozen liquid solution of belantamab mafodotin which includes ~30 participants from the 
ocular sub-study. Approximately 200 participants will be enrolled in the frozen liquid 
portion of the study. Approximately twenty-five additional participants will be enrolled 
into the independent lyophilized drug product cohort. 
4.3. 
Participant Completion 
A participant will be considered to have completed the study if he or she has received at 
least one dose of the study treatment and is in follow-up, or has died when the study is 
closed, and has not withdrawn consent from study participation.  
4.4. 
Scientific Rationale for Study Design 
Patients with RRMM who have relapsed after prior treatment with an anti-CD38 antibody 
and are refractory to a PI and an immunomodulatory agent represent a population of 
unmet medical need, for whom there is no approved treatment option. Given the clinical 
activity demonstrated in the BMA117159 study, treatment with belantamab mafodotin 
may offer a benefit to this patient population. It is also expected that due to its unique 
mechanism of action, belantamab mafodotin may be able to overcome the resistance to 
previously used drugs in the MM population.  
Belantamab mafodotin is the first-in-class ADC targeting BCMA. Preliminary clinical 
data for belantamab mafodotin monotherapy from Study BMA117159 among 35 
participants indicate an ORR of 60% [95% CI: 42.1%, 76.1%], with 51% of participants 
(n=18) having deep responses of VGPR or better. The median DoR has not been 
achieved, the 25th percentile for DoR is 6.7 months; the median PFS in this population 
was 7.9 months [95% CI: 3.1, NA]. Of note, the ORR for participants previously treated 
with daratumumab (n=14) was 43% (95% CI: 17.7, -71.1). Fifty nine percent of the 
treated population had 5 of more prior treatments.  
The response rate observed in this population is higher than response rates observed in 
similarly defined patient populations treated with other recently approved drugs (ORR 
ranging from 23.7% to 33.1% for Carfilzomib, pomalidomide and daratumumab) [Siegel, 
2012; Usmani, 2016; Kumar, 2008]. Given the evidence of clinical activity and 
manageable safety/tolerability profile demonstrated to date, the current evidence supports 
further development. 
The two-arm design with two dose levels and a futility analysis is justified for this 
population because there is no approved comparator for the proposed treatment setting. 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. At lower dose levels, the results were variable, with wide confidence 
intervals. In order to generate additional safety and efficacy data at a lower dose while 

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providing participants a chance of deriving clinical benefit, the dose of 2.5 mg/kg has 
been selected for additional testing (see Section 4.5 for dose justification). 
This design is appropriate for the selected patient population, since there is no approved 
standard of care in patients failing daratumumab. As shown in earlier studies on a similar 
population, the response rate is low and the mPFS is short in those patients. For example, 
in the pomalidomide + dexamethasone (PomDex) vs pomalidomide (Pom) study that 
enrolled patients with median of 5 prior lines, among whom 61% have been refractory to 
the mainstay of treatment, lenalidomide and bortezomib had an ORR of 18%, and mPFS 
of 2.7 months on Pom monotherapy arm [Richardson, 2014]. A similar Phase3 study of 
Pom with low dose dexamethasone (Pom/loDex) vs high dose dexamethasone (HiDex) 
has demonstrated an ORR of 3.9%, mPFS of 1.8 months, and mOS of 8 months in the 
HiDex arm where patients had a median of 5 prior lines, and 74% of them were double 
refractory to lenalidomide and bortezomib [Weisel, 2013]. 
Further, a randomized, phase III study which compared carfilzomib monotherapy against 
low-dose corticosteroids and optional cyclophosphamide in relapsed and refractory 
multiple myeloma has demonstrated an ORR of 11%, and OS of 10 months in 
populations previously treated with 5 lines of therapy and 63% of patients were double 
refractory to bortezomib and immunomodulatory agent [Hájek, 2017]. In summary, these 
examples provide indirect evidence that the prognosis of patients eligible for this protocol 
is poor, and that selected threshold for claiming success (33%) is appropriate since it 
doubles the expected ORR for those patients when treated with available agents.  
4.5. 
Dose Justification 
Belantamab mafodotin is currently being studied in the Phase I FTIH study, 
BMA117159. As of the clinical cut-off date of 26 June 2017, a total of 73 participants 
with RRMM have received at least 1 dose of belantamab mafodotin. 
Participants in Study BMA117159 were enrolled into the dose-escalation phase of the 
study (Part 1) at the following dose levels: 0.03 mg/kg (n=1), 0.06 mg/kg (n=1), 0.12 
mg/kg (n=4), 0.24 mg/kg (n=4), 0.48 mg/kg (n=4), 0.96 mg/kg (n=3), 1.92 mg/kg (n=4), 
2.50 mg/kg (n=8), 3.40 mg/kg (n=3), and 4.60 mg/kg (n=6). Based on the data from Part 
1 of the study, 35 participants were treated in the Dose Expansion portion (Part 2) at 3.4 
mg/kg Q3W. 
Clinical activity in Study BMA117159 
Clinical activity at the tested dose levels in Part 1 is summarized in Table 7. There were 
no dose-limiting toxicities (DLTs) observed during dose escalation; however, there was 
limited tolerability of the 4.6 mg/kg dose (prolonged fever, headache, severe fatigue).  

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Table 7 
Summary of Investigator-Assessed Best Response (with 
Confirmation; Study BMA117159 Part 1) 
Dose level (mg/kg) 
ORR (%) 
95%CI 
0.03 
0 
(0.0, 97.5) 
0.06 
0 
(0.0, 97.5) 
0.12 
0 
(0.0, 60.2) 
0.24 
0 
(0.0, 60.2) 
0.48 
0 
(0.0, 60.2) 
0.96 
33 
(0.8, 90.6) 
1.92 
25 
(0.6, 80.6) 
2.5 
0 
(0.0, 36.9) 
3.4 
100 
(29.2, 100.0) 
4.6 
50 
(11.8, 88.2) 
 
Preliminary clinical data from Part 2 of Study BMA117159 (3.4 mg/kg Q3W) indicated 
an Overall Response Rate (ORR) of 60% (95% CI: 42.1, 76.1) in an RRMM population 
(57% of participants had 5 or more lines of prior therapy, n=35). The median 
progression-free survival (mPFS) was 7.9 months (95% CI: 3.1, NA). The ORR was 
43% (95% CI: 17.7, 71.1) in the 14 participants who had received prior daratumumab. 
Clinical safety and tolerability in Study BMA117159 
In general, belantamab mafodotin has been well tolerated; the most frequent AEs were 
corneal events and thrombocytopenia/platelet count decrease, which were manageable 
following protocol-defined dose modification guidelines. Most participants in Study 
BMA117159 experienced dose reduction and/or dose delays; all events were graded 
using CTCAE Version 4.03. 
In the All Treated population (n=73), 35 participants (48%) had AEs that led to dose 
reduction. The most common AEs (frequency ≥5%) that led to dose reductions were 
vision blurred (18%), thrombocytopenia (8%), dry eye (5%), and keratitis (5%). In the 
Part 2 group (n=35), 23 participants (66. %) had AEs that led to dose reduction. The most 
common AEs (frequency ≥5%) that led to dose reductions were vision blurred (31%), 
thrombocytopenia (11%), keratitis (9%), photophobia (6%), platelet count decreased 
(6%), and infusion-related reactions (6%).  
Dose delays due to AEs were experienced by 38 participants (52%) in the All Treated 
population. The most common AEs (≥5%) leading to dose delays were vision blurred 
(22%), thrombocytopenia (8%), dry eye (7%), and keratitis (5%). Dose delays due to AEs 
were experienced by 25 participants (71%) in Part 2. The most common AEs (frequency 
≥5%) leading to dose delays were vision blurred (34%), thrombocytopenia (11%), dry 
eye (9%), keratitis (9%), lung infections (6%), and photophobia (6%).  
Rationale for evaluating 2.5 mg/kg in addition to 3.4 mg/kg in the current study 
A substantial number of participants treated at 3.4 mg/kg dose required a dose delay 
and/or dose reduction due to an AE. Responders in the 3.4 mg/kg dose group in Part 2 
maintained their responses with dose reductions and delays. Based on the available data, 
evaluation of a lower dose level in addition to the 3.4 mg/kg dose is being done to ensure 
that the appropriate dose of belantamab mafodotin has been selected for monotherapy 

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treatment. Although no responses were observed at the 2.5 mg/kg dose in Study 
BMA117159, one response was noted at each of the lower doses of 0.96 mg/kg (1 in 3 
participants) and 1.92 mg/kg, and (1 in 4 participants). In addition, estimated receptor 
binding saturation was seen at doses 1.92 mg/kg.  
The next highest dose level to 3.4 mg/kg is 2.5 mg/kg, a dose reduction of ~25%. The 
preliminary population pharmacokinetic analysis estimated that the between-participant 
variability in belantamab mafodotin clearance was ~50%, and the variability in Cmax 
values was ~20%; therefore, some overlap in exposure is expected between the two dose 
levels. Despite this pharmacokinetic overlap, the Bayesian logistic regression modeling 
based on the full clinical dataset (see below) indicated that a dose level of 2.5 mg/kg had 
a lower predicted response rate as well as a lower predicted rate of Grade 2 corneal 
event. The next lower dose level, 1.92 mg/kg, had a much lower predicted response rate 
and was not considered suitable for further exploration. Therefore, 2.5 mg/kg was 
selected as the second dose level for evaluation in this study. The interim analysis will 
help to minimize exposure to a potentially less effective dose level.  
Bayesian logistic regression model of dose-response for ORR and corneal event rate 
To further explore the dose selection, Bayesian logistic regression model (BLRM) was 
used to determine the dose-response relationships for both ORR and ≥Grade 2 corneal 
event rate (as determined by NCI CTCAE grading) separately using all 73 participants 
with RRMM in Study BMA117159 (Figure 2). Table 8 displays the predicted response 
rate and predicted Grade 2 corneal event rate at dose levels of 3.4, 2.5, and 1.92 mg/kg. 
The model showed that the posterior probability of observing an ORR ≥30% is 100% in 
the 3.4 mg/kg dose group, 83% in the 2.5 mg/kg dose group, and 29% in the 1.92 mg/kg 
dose group. Similarly, the posterior probability of observing ≥Grade 2 corneal event rate 
is also higher in the 3.4 mg/kg dose group.  
Figure 2 
Fitted Dose-Response Plot for ORR and ≥ Grade 2 Corneal Event 
Rate 
 

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Table 8 
Summary of Predicted Mean Response and Mean ≥Grade 2 Corneal 
Event* and 95% Credible Intervals (Parts 1 and 2, Study BMA117159) 
Dose (mg/kg) 
Predicted response rate (%) 
(95% credible interval) 
Predicted G2 corneal AE rate (%) 
(95% credible interval) 
1.92 
25.3 (9.4, 42.2) 
33.7 (18.3, 49.0) 
2.5 
37.0 (22.3, 51.6) 
43.4 (30.2, 56.9) 
3.4 
53.7 (40.3, 66.9) 
55.7 (42.3, 68.7) 
*Predicted values are based on the posterior distribution of response rate and corneal event rate per CTCAE 4.03 
 
In summary, based on the safety, tolerability, and clinical activity observed to date, 
2.5 mg/kg and 3.4 mg/kg were selected as the appropriate dose levels of belantamab 
mafodotin to be further studied in this phase 2 study. The dose may be further 
individually adjusted in participants experiencing adverse events, according to the 
guidance in the protocol.  
Overall, there were no new safety signals identified in the 205678 study, and the profile 
of adverse events was similar to the experience in BMA117159 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.  
In summary, the selection of the dose of 2.5 mg/kg Q3W for future single agent studies 
with belantamab mafodotin is based on the available data with single agent belantamab 
mafodotin in heavily pretreated patients with relapsed/refractory MM from 2 studies: 
BMA117159 and 205678, which showed clinically meaningful efficacy with a 
manageable safety profile in a heavily pre-treated patient population. 
4.6. 
End of Study Definition 
The study will end when all participants including the participants in PACT phase have 
either died, progressed, or have withdrawn consent. 
 
A final DCO representing the end of data collection, prior to the EOS, is defined as 39 
months post LSFD. Following the final DCO date the study will move into the PACT 
phase and the clinical study database will be closed to new data. Participants who are 
receiving belantamab mafodotin may continue to receive belantamab mafodotin if they 
are gaining clinical benefit as assessed by the investigator until they meet any protocol-
defined treatment discontinuation criteria. Participants in survival follow-up at the time of 
the final DCO date will be considered to have completed the study. Although the clinical 
study database will be closed at the time of the final DCO date, the study remains open 
until all participants discontinue study treatment and complete the 70-day safety follow-
up and the EOS is reached. 
 
The EOS is defined as the date of the last visit of the last participant in the study. A 
participant is considered to have completed the study if he/she has completed all periods 
of the study including the last visit. 

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5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, are not permitted.  
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
1. Provide signed written informed consent, which includes compliance with the 
requirements and restrictions listed in the consent form 
2. Male or female, 18 years or older (at the time consent is obtained)  
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Appendix 
8) 
4. Histologically or cytologically confirmed diagnosis of MM as defined according to 
IMWG, [Rajkumar, 2014] criteria, and  
 
a) Has undergone stem cell transplant or is considered transplant ineligible, and 
  
b) Has failed at least 3 prior lines of anti-myeloma treatments, including an anti-
CD38 antibody (e.g., daratumumab) alone or in combination, and is refractory to 
an immunomodulatory agent (i.e., lenalidomide or pomalidomide), and to a 
proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib). The number of 
prior lines of therapy will be determined according to the guidelines in 
Rajkumar, 2015. 
 
Refractory myeloma is defined as disease that is nonresponsive while on 
primary or salvage therapy, or progresses within 60 days of last therapy. 
Nonresponsive disease is defined as either failure to achieve at least minimal 
response or development of progressive disease (PD) while on therapy 
[Rajkumar, 2011] 
5. Has measurable disease with at least one of the following: 
a. 
Serum M-protein 0.5 g/dL (5 g/L) 
b. Urine M-protein 200 mg/24h 
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) 
6. Participants with a history of autologous stem cell transplant are eligible for study 
participation provided the following eligibility criteria are met: 
a. 
transplant was >100 days prior to study enrolment 
b. no active infection(s) 
c. 
participant meets the remainder of the eligibility criteria outlined in this protocol 
7. Adequate organ system functions as defined in Table 9. 

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Table 9 
Criteria for Determining Adequate Organ System Function  
System 
Laboratory Values 
Hematologic 
Absolute neutrophil count (ANC) 
1.0 X 109/L 
Hemoglobin 
8.0 g/dL 
Platelets 
50 X 109/L 
Hepatic 
 
Total bilirubin 
≤1.5X ULN  
(Isolated bilirubin ≥1.5xULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%) 
ALT 
2.5 X ULN 
Renal 
eGFRa 
Spot urine (albumin/creatinine ratios (spot urine) 
30 mL/min/ 1.73 m2  
<500 mg/g (56 mg/mmol) 
Cardiac 
LVEF (Echo) 
45% 
a. 
As calculated MDRD equation (Appendix 10) 
Note: Laboratory results obtained during Screening must be used to determine eligibility criteria. In situations 
where laboratory results are outside the permitted range, the investigator may retest the participant and the 
subsequent within range screening result may be used to confirm eligibility. 
 
8. Female Participants: Contraceptive use by men or 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 one 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, during the 
intervention period and for at least 80 days after the last dose of study 
intervention 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. 
 
A WOCBP must have a negative highly sensitive serum pregnancy test (as 
required by local regulations) within 72 hours before the first dose of study 
intervention.  
 
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. 
9. Male Participants: Contraceptive use by men or women should be consistent with 
local regulations regarding the methods of contraception for those participating in 
clinical studies.  

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Male participants are eligible to participate if they agree to the following during the 
intervention period and for at least 140 days:  
• 
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 and female partner to use an additional highly 
effective contraceptive method with a failure rate of <1% per year as when 
having sexual intercourse with a woman of childbearing potential who is not 
currently pregnant.  
10. All prior treatment-related toxicities (defined by National Cancer Institute- Common 
Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03, must be ≤Grade 1 
at the time of enrolment except for alopecia and Grade 2 peripheral neuropathy. 
11. (France only) A participant will be eligible for inclusion in this study only if either 
affiliated to or a beneficiary of a social security category. 
 
5.2. 
Exclusion Criteria 
Participants satisfying any of these criteria are not eligible for assignment to treatment: 
1. Systemic anti-myeloma therapy within ≤14 days or 5 half-lives, whichever is 
shorter, or plasmapheresis within 7 days prior to the first dose of study drug 
2. Systemic treatment with high dose steroids (equivalent to 60 mg prednisone 
daily for ≥4 days) within the past 14 days if administered to treat MM or non- 
MM disease 
3. Symptomatic amyloidosis, active ‘polyneuropathy, organomegaly, 
endocrinopathy, myeloma protein, and skin changes’ (POEMS) syndrome, 
active plasma cell leukemia at the time of screening.  
4. Prior allogeneic stem cell transplant 
5. Current corneal epithelial disease except mild punctate keratopathy  
6. Use of an investigational drug within 14 days or five half-lives, whichever is 
shorter, preceding the first dose of study drug. Prior treatment with a 
monoclonal antibody within 30 days of receiving the first dose of study drugs. 
Prior BCMA targeted therapy.  
7. Evidence of active mucosal or internal bleeding 
8. Any major surgery within the last four weeks 

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9. 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 9. 
10. 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.  
11. Current unstable liver or biliary disease per investigator assessment defined by 
the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, 
esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable 
chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) 
or hepatobiliary involvement of malignancy is acceptable if participant 
otherwise meets entry criteria. 
12.  Malignancies other than disease under study are excluded, except for any other 
malignancy from which the participant has been disease-free for more than 2 
years and, in the opinion of the principal investigators and GSK Medical 
Monitor, will not affect the evaluation of the effects of this clinical trial treatment 
on the currently targeted malignancy (MM). Participants with curatively treated 
non-melanoma skin cancer may be enrolled. 
13. Evidence of cardiovascular risk including any of the following: 
a. 
QTcF interval QTcF > 480 msec (the QT interval values must be corrected 
for heart rate by Fridericia’s formula [QTcF]) 
b. Evidence of current clinically significant uncontrolled arrhythmias, 
including clinically significant ECG abnormalities such as 2nd degree 
(Type II) or 3rd degree atrioventricular (AV) block. 
c. 
History of myocardial infarction, acute coronary syndromes (including 
unstable angina), coronary angioplasty, or stenting or bypass grafting within 
six months of Screening. 
d. Class III or IV heart failure as defined by the New York Heart Association 
functional classification system [NYHA, 1994] 
e. 
Uncontrolled hypertension 
14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs 
chemically related to belantamab mafodotin, or any of the components of the 
study treatment. 
15. Pregnant or lactating female. 
16. Active infection requiring antibiotic, antiviral, or antifungal treatment. 
17. Known HIV infection. 
18. Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody 
(HBcAb at screening or within 3 months prior to first dose of study treatment 
19. 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.  

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Note: Participants with positive Hepatitis C antibody due to prior resolved 
disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is 
obtained. 
Note: Hepatitis RNA testing is optional and participants with negative Hepatitis 
C antibody test are not required to also undergo Hepatitis C RNA testing. 
 
5.3. 
Lifestyle Restrictions 
Contact lenses are prohibited while the participant is on study. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently enrolled. 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 to be entered into INFORM 
includes demography, screen failure details, eligibility criteria, and any serious adverse 
events (SAEs). 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened. Rescreened participants must be assigned a new unique participant 
number that is different from the initial number. 
6. 
TREATMENTS 
Study treatment is defined as any investigational treatment intended to be administered to 
a study participant according to the study protocol. Belantamab mafodotin will be 
administered intravenously.  
Belantamab mafodotin will be administered intravenously, at the study sites, as either 2.5 
mg/kg or 3.4 mg/kg calculated dose.  

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Product name: 
Belantamab mafodotin  
Dosage form: 
Frozen liquid, 30 mg/vial solution in single-use vial 
or  
Lyophilized powder, 100 mg/vial in single-use vial for reconstitution 
(independent cohort with approximately 25 participants) 
(Participants continuing treatment in PACT phase after final analysis may 
receive lyophilized study drug.) 
Unit dose strength(s)/Dose 
Level(s): 
30 mg/vial / 2.5 or 3.4 mg/kg (Frozen liquid)  
or  
100 mg/vial / 2.5 or 3.4 mg/kg (Lyophilized powder) 
Route of Administration 
Delivered as IV solution over at least 30 minutes*.  
Dosing instructions: 
Dilute belantamab mafodotin in normal 0.9% saline to the appropriate 
concentration for the dose. Doses of belantamab mafodotin are to be 
administered as an IV infusion via an infusion pump. See Investigator’s 
Brochure for compatible administration materials. 
 
For lyophilized powder only: Reconstitute belantamab mafodotin lyophilized 
powder 100 mg/vial 2.0mL of water for injection (WFI); dilute with saline 
before use.  
Manufacturer/ Source of 
Procurement: 
GSK/Baxter 
*Infusions may be prolonged in the event of an infusion reaction. If multiple participants experience clinically significant 
infusion reactions, the infusion rate may be slowed for all future administrations of study treatment(s) for all 
participants. Should this global change in infusion rate be required, it will be communicated to the sites in writing. 
6.1. 
Belantamab Mafodotin Treatments Administered 
Belantamab mafodotin is to be administered at a calculated dose of 2.5 mg/kg or 3.4 
mg/kg as an IV infusion, via an infusion pump. Administration of belantamab mafodotin 
will be documented in the clinic source documents and reported in the electronic case 
report form (eCRF). The time of start and end of infusion will be documented in eCRF. 
Belantamab mafodotin will be administered on Day 1 of each cycle. Premedication is not 
required prior to infusion unless deemed medically necessary by the investigator, in 
which case it should be administered according to institutional recommendations.  
Any participant experiencing an IRR must receive appropriate medical treatment. When 
the participant’s condition is stable, the infusion may be restarted at a slower rate. For 
details on restarting the belantamab mafodotin infusion after interruption for IRR, please 
see Table 11. 
In general, upon restarting, the infusion rate must be decreased by half at the time the 
infusion was interrupted.  
Participants will be treated until disease progression, or until death, or until unacceptable 
toxicity (including but not restricted to meeting stopping criteria as outlined in Section 
7.1).  
Participants continuing treatment during PACT phase after final analysis may receive 
lyophilized study drug. Lyophilized belantamab mafodotin 100 mg/vial is supplied as a 
white to yellow powder in a single-dose vial for reconstitution and further dilution. 

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6.2. 
Dose Modification 
Dose modifications will be managed according to Dose Reduction Criteria and Guidance 
provided in Table 11 and Table 12. 
6.2.1. 
Adjustments Due to Body Weight 
The actual body weight in kg at baseline (assessed on Cycle 1 Day 1 prior to dosing) will 
be used for dose calculation of belantamab mafodotin in all participants during the 
treatment period. However, if the change of body weight is greater than 10%, the dose 
must be recalculated based on the actual body weight at the time of dosing.  
6.2.2. 
Dose Reductions for Toxicity 
After Cycle 1, participants may have their dose delayed or reduced for toxicities 
according to the recommendations.  
See Table 11 for dose modifications guidelines for belantamab mafodotin for specific 
toxicity related AEs and Table 12 for guidelines for drug-related toxicities, not otherwise 
specified AEs.  
See Table 13 for dose modification guidelines for cornea-related AEs associated with 
belantamab mafodotin.  
Permitted dose reductions for belantamab mafodotin are shown in Table 10. 
Table 10 
Permitted Dose Reductions 
Starting dose 
1st reduction 
2nd reduction 
3.4 mg/kg 
2.5 mg/kg 
1.92 mg/kg 
2.5 mg/kg 
1.92 mg/kg 
-- 
 
• 
If the participant cannot tolerate the drug after the allowed dose reductions, he or 
she must be withdrawn from the study for lack of tolerability. 
• 
Only 1 dose reduction (to 1.92 mg/kg) is permitted for the lower starting dose of 
2.5 mg/kg. 
• 
In case of full resolution of symptoms which lead to dose reduction, further 
treatment at the previous dose may be considered by the investigator.  
Dosing delays are permitted in the case of medical/surgical events or for logistical 
reasons not related to study therapy (e.g., elective surgery, unrelated medical events, 
participant vacation, and/or holidays, but not for participants’ decision to delay 
treatment). If a dose is delayed, the participant should wait for the next scheduled dose to 
resume treatment. In individual cases where in the judgement of an investigator waiting a 
full cycle to resume treatment after delay (skipping dose) related to toxicity which has 
resolved would be detrimental to patient’s health- the Principal Investigator should 
contact Medical Monitor to discuss an earlier re-start. An earlier re-start may be 
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dosing with belantamab mafodotin cannot occur more frequently than every 21 days ( 3-
day window). In such cases efficacy and safety assessments must continue to be 
conducted every 3 weeks in line with initial efficacy and safety assessments on study, 
which may result in 2 separate visits (1 for dosing, 1 for disease assessments) (Table 2).  
Evaluations associated with a Dose (Table 2) would be entered into the eCRF under the 
next scheduled cycle.  
The reason for any dose delay must be documented in the participant's eCRF and clinic 
record. 
Resuming treatment with belantamab mafodotin will be possible with or without dose 
reduction after the toxicity has resolved to Grade 1 or less.  
Table 11 
Dose Modification Guidelines for Belantamab Mafodotin-Related 
Adverse Events 
Toxicity 
Grade/description 
of toxicity 
Recommendations for belantamab mafodotin 
Elevated serum creatinine 
which cannot be explained by 
concomitant sepsis, TLS, other 
severe condition with fever, or 
dehydration 
If absolute serum 
creatinine 
increases from 
baseline by >0.5 
mg/dL 
• 
Repeat serum creatinine within 48 hours 
• 
If confirmed: withhold therapy, institute treatment and 
monitoring as clinically indicated, and follow for 
resolution 
• 
Discuss any further dosing with Medical Monitora 
Serum creatinine >Grade 3 
>3.0 mg/dL from 
baseline 
or 
3.0-6.0xULN 
• 
Provide appropriate medical treatment. 
• 
Permanently discontinue treatment with belantamab 
mafodotin  
Spot urine (albumin / 
creatinine ratios) 
>2000 mg/g 
(or 224 mg/mmol) 
• 
Re-test (at least 7 days apart). 
• 
If not confirmed, continue belantamab mafodotin at 
100% dose 
• 
If confirmed on re-test and no clear evidence of 
disease progression 
o 
Interrupt treatment with belantamab mafodotin 
o 
Repeat testing within 4 weeks 
i. 
If spot urine <2000 mg/g (224 mg/mmol), 
may restart belantamab mafodotin with a 
dose reduction 
ii. 
If spot urine remains >2000 mg/g 
(224 mg/mmol) after 4 weeks, 
permanently discontinue belantamab 
mafodotin and withdraw participant from 
study; provide treatment as clinically 
indicated and follow for resolutiona 
Thrombocytopenia (on days of 
dosing  
3 or 4 
• 
Withhold treatment until thrombocytopenia recovered 
to Grade 2 or less (≤G2). 
• 
If Grade 3-4 thrombocytopenia is considered disease-
related, treatment may be continued with more 
frequent hematology monitoring, until recovery to 
Grade 2 or less. Dose reduction should be 
considered in those patients 
• 
Implement supportive treatment (e.g. transfusion) as 
clinically indicated and per local practice. 

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Toxicity 
Grade/description 
of toxicity 
Recommendations for belantamab mafodotin 
Febrile neutropenia 
 Defined as: single 
temp of 38.3oC, or 
sustained 38oC for 
>1 hr. AND ANC 
<1.0 x 109/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 a dose reduction of 
belantamab mafodotin, if neutropenia was drug 
related 
Neutropenia  
Grade ≥3 (Defined 
as ANC <1.0x109/L 
• 
If noted on Day 1 of any cycle, withhold belantamab 
mafodotin. Consider more frequent hematology 
(CBC) monitoring as clinically indicated, until recovery 
to Grade 2 or less.  
• 
Resume belantamab mafodotin at pre-held dose once 
neutropenia recovers to Grade ≤ 2 (ANC ≥ 1.0x109/L) 
• 
Implement supportive care as clinically indicated and 
per local practice. 
In case of 
recurrence of 
frequent episodes 
of neutropenia 
<1.0 × 109 /L 
• 
Consider dose reduction of belantamab mafodotin, if 
it was drug-related. 
Infusion Reactionb 
2 
• 
Stop the infusion, provide medical treatment and 
continue at half the original infusion rate after 
resolution to Grade 0-1 
3 
• 
Further treatment with belantamab mafodotin needs 
to be discussed with Medical Monitor. Continuation 
only allowed after recovery to Grade 1 and with pre-
medication, and extension of infusion time to 2-4 
hours. Any future infusion needs to be pre-medicated 
4 
• 
Permanently discontinue 
Pneumonitis 
2 
• 
Continue treatment when toxicity resolves to Grade 
0-1 
Grade 3-4 
• 
Permanently discontinue 
a. 
Medical Monitor may consult GSK's nephrotoxicity panel about plans to continue therapy. 
b. 
If symptoms resolve within one hour of stopping infusion, the infusion may be restarted at 50% of the original 
infusion rate (e.g., from 100 mL/hr. to 50 mL/hr.). Otherwise dosing will be held until symptoms resolve and the 
participant must be pre-medicated for the next scheduled dose. 

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Table 12 
General Dose Modification and Management Guidelines for Drug- 
related Adverse Events Not Otherwise Specifieda 
Severity 
Management 
Follow-up 
Grade 1 
• 
Administer symptomatic 
treatment as appropriate 
• 
Continue study drug(s)a 
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: 
o Delay study drugb, or consider dose reduction by 25% 
If recovery takes >3 weeks- consult GSK MM  
• 
If symptoms continue or worsen to Grade 3-4, see below 
Grade 3 
• 
Provide appropriate medical 
treatment  
• 
Consider Consulting 
subspecialist 
Delay treatment till recovery to G1 or less. Consider dose 
reduction. Consider consultation with GSK MM. 
Exceptions: Participants who develop G3 toxicities which 
respond to standard treatment and resolve to ≤G1 within 48 
hours may continue treatment at scheduled or reduced 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. 
Treatment-related decisions can be made based on local laboratory results if central results are not available or 
delayed. 
b. 
In case a dose is delayed, the participant should wait for the next scheduled dose to resume treatment. 
 
 

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Table 13 
Dose Modification Guidelines for Belantamab Mafodotin Treatment-
Related Corneal Events  
Grade per GSK/KVA 
scale 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
*Recommended 
Dosage 
Modifications 
Continue 
treatment at 
current 
dose. 
Withhold 
belantamab 
mafodotin until 
improvement in 
both corneal 
examination 
findings and 
changes in 
BCVA to 
Grade 1 or 
better and 
resume at 
same dose. 
Withhold 
belantamab 
mafodotin until 
improvement in 
both corneal 
examination 
findings and 
changes in 
BCVA to Grade 
1 or better and 
resume at 
reduced dose. 
 
If already on 
lowest dose, 
participant 
should continue 
treatment after 
recovery to 
Grade 1 or better 
with the same 
dose. 
 
Consider 
permanent 
discontinuation of 
belantamab 
mafodotin.  
 
If based on 
benefit risk 
assessment, 
treatment of 
belantamab 
mafodotin is 
being considered, 
withhold 
treatment until 
improvement in 
both corneal 
examination 
findings and 
change in BCVA 
to Grade 1 or 
better and 
resume at 
reduced dose. 
If already on 
lowest dose, 
participant should 
continue 
treatment after 
recovery to Grade 
1 or better with 
the same dose. 
Corneal 
Management Care 
Regardless of 
Grade  
Preservative-free artificial tears: 
Increase to 1 drop as frequently as every 2 hours, as needed 

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Grade per GSK/KVA 
scale 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Based on exam findings and symptoms the treating 
ophthalmologist may prescribe additional treatments (e.g. steroid 
eye drops, bandage contact lens, topical treatments, etc.) 
*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. 
6.2.3. 
Corneal Supportive Care Guidelines 
Corneal events, which commonly manifests as a superficial microcystic keratopathy, has 
been observed with antibody drug conjugates, including those conjugated to MMAF.  
Further information regarding corneal event associated with belantamab mafodotin, 
including a GSK/KVA (Keratopathy Visual Acuity) scale for treatment related corneal 
toxicities and prophylactic measures are in Appendix 9. 
Sites are required to establish a close collaboration with an ophthalmologist (or 
optometrist, if an ophthalmologist is not available) who will be responsible for assessing 
participants and managing those who develop a corneal event in close communication 
with GSK Medical Monitor and possibly a GSK ophthalmologist.  
Participants will be assessed by ophthalmologists (or optometrist, if an ophthalmologist is 
not available) at baseline and every three weeks. If there are no corneal events at time of 
the Cycle 4 exam, participants may have their ophthalmologic exams decreased to once 
every 3 months. If a participant subsequently develops ocular symptoms, the participant 
should be evaluated by an ophthalmologist (or optometrist, if an ophthalmologist is not 
available). Intraocular pressure must be monitored if steroid eye drops are used 
continuously for more than 7 days. 
Participants who have corneal signs per the GSK/KVA Scale present at end of study will 
continue to be followed at 3 and 6 weeks after the EoT visit and then every 6 weeks for 
up to 12 months, or until full resolution of ophthalmic changes, or deemed clinically 
stable by an ophthalmologist (an optometrist if an ophthalmologist is not available), 
whichever comes first. Clinically stable is defined as: 
• Any GSK/KVA Grade 1 exam finding (mild keratopathy) and a one-line change 
in vision when compared to baseline or,  
• No exam findings, and a one-line change when compared to baseline or,  
• Any GSK/KVA Grade 1 exam finding (mild keratopathy) and no change in vision 
from baseline 
 At the selected sites, participants in the ocular sub-study will undergo additional 
ophthalmic exams (see Section 8.2.10). 

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6.3. 
Method of Treatment Assignment 
The Sponsor will supply a range of unique numbers to each site and participants eligible 
for enrolment will be assigned a unique Participant Number by the site. 
Before the study is initiated, log-in directions for the central Interactive Response 
Technology (IRT) system will be provided to each site to be used to for study drug 
supply. 
Participant numbers are unique will not be reassigned to another participant if a 
participant assigned a number is found to be a Screen Failure.  
Participants will be assigned to study treatment in accordance with the randomization 
schedule. 
Participants will be identified by a unique participant number that will remain consistent 
for the duration of the study. 
Upon completion of all the required screening assessments, eligible participants will be 
registered into the Registration and Medication Ordering System (RAMOS), the GSK 
Interactive Response Technology (IRT, by the investigator or authorized site staff. 
RAMOS allows study sites to register and randomize participants, and also records 
stratification information. 
The following information for stratification must be entered into the system to obtain the 
treatment assignment: 
• number of prior lines of therapy (≤4 vs >4); 
• cytogenetic risk categories (high risk defined as t(4;14), t(14;16), and 17p13del vs 
non-high risk - all others); 
Randomization will be done centrally using a randomization schedule generated by the 
GSK Clinical Statistics Department, which will assign participants in a 1:1 ratio to: 
• Arm 1: 3.4 mg/kg IV Q3W  
• Arm 2: 2.5 mg/kg IV Q3W  
Once a randomization number has been assigned it must not be re-assigned even in cases 
of errors. 
In the lyophilized cohort participants will be assigned the 3.4 mg/kg dose level, unless the 
results of the IA indicate that it should not be continued. In that case, the 2.5 mg/kg dose 
level will be assigned to participants.  
RAMOS Study Specific User Guide and Clinical Support Helpdesk contact information 
will be provided to the study site in the SRM. 

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6.4. 
Blinding 
This will be an open-label, 2-arm monotherapy study with an additional independent 
cohort enrolled after lyophilized product is available. Therefore, sponsor will have access 
to the participant level data throughout the study. However, there will be no intention to 
summarize and interpret data from the ongoing study at any time point except the pre-
defined analyses. 
In the ocular sub-study of participants (Section 8.2.10 and Appendix 9), the treating 
ophthalmologist will remain blinded as to which eye receives the prophylactic 
corticosteroid treatment. 
6.5. 
Preparation/Handling/Storage/Accountability 
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatment received and any discrepancies are 
reported and resolved before use of the study treatment. 
Only participants enrolled in the study may receive study treatment and only authorized 
site staff may supply or administer study treatment. All study treatments 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 treatment accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation, and final disposition records). 
Further guidance and information for the final disposition of unused study treatment are 
provided in the Study Reference Manual.  
Under normal conditions of handling and administration, study treatment is not expected 
to pose significant safety risks to site staff. Take adequate precautions to avoid direct eye 
or skin contact and the generation of aerosols or mists. In the case of unintentional 
occupational exposure notify the monitor, Medical Monitor, or GSK study contact. 
A Material Safety Data Sheet (MSDS)/equivalent document describing occupational 
hazards and recommended handling precautions either will be provided to the 
investigator, where this is required by local laws, or is available upon request from GSK. 
In the case of unintentional occupational exposure notify the monitor, Medical Monitor, 
or GSK study contact. 
6.6. 
Treatment Compliance 
Belantamab mafodotin will be administered intravenously to participants at the site. 
Administration will be documented in the source documents and reported in the eCRF. 
Study treatment is based on body weight calculation and may be reduced for toxicity for 
individual participants according to protocol guidelines.  

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Participants will receive study treatment at the site 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 and reported in the eCRF. The dose of 
study treatment 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 
treatment and documented in source.  
6.7. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrolment 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 or prior 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 end of the study (Final 
Study Visit). Any concomitant medication(s), including non-prescription medication(s) 
and herbal product(s), taken during the study will be recorded in the electronic case 
report form (eCRF). Additionally, a complete list of all prior anti-cancer therapies will be 
recorded in the eCRF. 
If future changes are made to the list of permitted/prohibited medications, formal 
documentation will be provided by GSK and stored in the study file. The SRM will be 
updated to include this information. Any such changes will be communicated to the 
investigative sites in the form of a letter. 
6.7.1. 
Permitted Medication(s) 
Participants should receive full supportive care during the study, including transfusions of 
blood products, growth factors, and treatment with antibiotics, anti-emetics, antidiarrheal, 
and analgesics, as appropriate. Concomitant therapy with bisphosphonates is allowed. 
Participants may receive local irradiation for pain or stability control.  
6.7.2. 
Prohibited Medication(s) 
Chronic treatment with oral steroids is prohibited while the participant is on study, unless 
for treatment of acute complications related to study treatment, or pre-medication prior to 
belantamab mafodotin infusion. Steroids may be used to treat infusion-related reactions. 
Inhaled steroids are allowed for management of asthma or COPD exacerbations. Chronic 
low dose replacement therapy (less than or equal to 10 mg prednisolone) is allowed in 
participants with adrenal insufficiency. 

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Elimination pathways for belantamab mafodotin and cys-mcMMAF have not been 
characterized in humans. Cys-mcMMAF was not an inhibitor, an inducer, or a good 
substrate of cytochrome P450 enzymes in vitro. Cys-mcMMAF was shown to be a 
substrate of P-glycoprotein (P-gp) and Organic Anion Transporting Proteins (OATP) 1B1 
and 1B3 transporters in vitro. Caution should be exercised when belantamab mafodotin is 
combined with strong inhibitors of P-gp, and strong inhibitors of OATP1B1 and 
OATP1B3 should be avoided unless considered medically necessary. See the SRM for 
more information. 
Other prohibited therapies include: 
• 
Plasmapheresis: prohibited from 7 days prior to first dose through the end of 
study.  
• 
Any other anti-cancer therapy not specified in this protocol, and any 
investigational agents other than belantamab mafodotin. 
6.7.3. 
Prohibited Device(s) 
Contact lenses are prohibited while the participant is on study. 
6.8. 
Continued Access to Study Intervention after the End of the 
Study 
Study participants that continue to benefit from study intervention beyond the DCO date 
will continue to have access to study intervention until the EOS as defined in Section 4.6. 
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.  
Refer to the SoA (Table 3) for follow-up assessments of participants who are to be 
followed for disease progression and survival after they permanently discontinue from 
study drug until DCO date.  
 
6.8.1. 
Continued Access to Study Intervention After Data Cut-off prior 
to EOS (PACT Phase) 
Participants receiving belantamab mafodotin following 39 months post LSFD, may 
continue to receive belantamab mafodotin, if in the opinion of their treating physician, 
they are benefiting from continued treatment, and they do not meet any protocol-defined 
treatment discontinuation criteria (see Section 7). Study treatment will continue until a 
study treatment discontinuation criterion (see Protocol Section 7), as assessed by the 
investigator, has been met. 
Participants who continue study treatment in the PACT phase will be cared for in 
accordance with local standard clinical practice. Additional guidance on treatment with 
the study drug, patient management, dispensing of study treatment and maintaining study 

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drug accountability in the PACT phase is provided in the SRM. Information relating to 
participant care will be recorded on their medical records. Participants will continue to be 
monitored for all SAEs, AEs leading to treatment discontinuation, overdoses, pregnancy 
cases and pre-specified ocular data that must be reported to GSK on paper form until 70 
days after the participant’s last dose of study treatment in accordance with Section 8.2 
(Reporting of Serious Adverse Events). Pre-specified ocular data will also be reported 
until resolution unless the event is considered by the investigator to be unlikely to 
resolve, or the patient is lost to follow up. For dispensing of study treatment and 
maintaining study drug accountability in the PACT phase please refer to the SRM. All 
other assessments will revert to standard of care at their site. 
 
7. 
DISCONTINUATION CRITERIA 
7.1. 
Discontinuation of Study Treatment 
Participants will receive study treatment until disease progression, unacceptable toxicity, 
or death (including but not restricted to meeting stopping criteria for significant toxicity 
as outlined in Section 7.1).  
Study treatment may be permanently discontinued for any of the following reasons: 
• 
disease progression or unacceptable toxicity. 
• 
participant has met any of the protocol defined safety stopping criteria 
(Section 6.2). 
• 
deviation(s) from the protocol 
• 
request of the participant or proxy (withdrawal of consent by participant or 
proxy) 
• 
investigator’s discretion 
• 
concurrent illness that prevents further administration of study treatment(s) 
• 
pregnancy  
• 
participant is lost to follow-up  
• 
study is closed or terminated 
The primary reason study treatment was permanently discontinued must be documented 
in the participant’s medical records and electronic case report form (eCRF)  
If the participant voluntarily discontinues from treatment due to toxicity, AE (adverse 
event) must be recorded as the primary reason for permanently discontinuation on the 
eCRF.  
Once a participant has permanently discontinued from study treatment, the participant 
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All participants who discontinue from study treatment for any reason other than 
confirmed progression or death will complete safety assessments, and will be followed up 
for PFS, OS, and subsequent anti-cancer therapy after study as specified in the SOA 
(Table 1).  
PFS Follow-up: 
All participants who permanently discontinue study treatment in the absence of disease 
progression will remain in the study and will be followed for progression according to the 
protocol schedule until: 
• 
New anti-cancer therapy is initiated 
• 
Progression is documented, or  
• 
Death occurs 
 
OS Follow-up: 
All participants who permanently discontinue study treatment will be followed for 
survival and new anti-cancer therapy until the end of study as described in Section 4.3.  
Withdrawal from Study Treatment: 
A participant may withdraw from study treatment at any time at his/her own request or 
may be withdrawn at any time at the discretion of the investigator for safety, behavioral 
or administrative reasons. If a participant withdraws from the study, he/she may request 
destruction of any samples taken, and the investigator must document this in the site 
study records.  
7.2. 
Safety Stopping Criteria 
7.2.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event. The diagram below illustrates Liver 
Stopping Event Algorithm (Figure 3)  

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Figure 3 
Liver Chemistry Stopping Criteria – Liver Stopping Event Algorithm 
 
The details on follow up procedures are outlined in Appendix 7. 
7.2.2. 
Study Treatment Restart or Rechallenge 
If participant meets liver chemistry stopping criteria do not restart/rechallenge participant 
with study treatment unless: 
• 
GSK Medical Governance approval is granted (as described below), 
• 
Ethics and/or IRB approval is obtained, if required, and 
• 
Separate consent for treatment restart/rechallenge is signed by the participant 
If GSK Medical Governance approval to restart/rechallenge participant with study 
treatment is not granted, then participant must permanently discontinue study treatment 
and may continue in the study for protocol-specified follow up assessments. 
7.2.3. 
Left Ventricular Ejection Fraction (LVEF) Stopping Criteria 
Echocardiography must be performed at Screening. If an ECHO is done at any point 
during the study, the following stopping criteria are to be employed. Participants who 
have an asymptomatic absolute decrease of >10% in LVEF and the ejection fraction is 
below the institution’s lower limit of normal (LLN) should temporarily discontinue study 
treatment and have a repeat evaluation of LVEF within 1 week. Echocardiogram (ECHO) 
should be repeated every 1 to 2 weeks for 4 weeks or until LVEF recovery to above 
institutional LLN and within 10% of baseline.  

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• 
If the LVEF recovers (defined as  institutional LLN and absolute decrease 
10% compared with baseline) at any time during the next 4 weeks, after 
consultation with and approval from the GSK medical monitor, the participant 
may be restarted on belantamab mafodotin at a reduced dose. For such 
participants, monitoring of LVEF will be performed 2 and 4 weeks after re-
challenge, then every 4 weeks for a total of 16 weeks. 
• 
If repeat LVEF does not recover within 4 weeks, treatment must be permanently 
discontinued. Ejection fraction must be monitored every 4 weeks for a total of 
16 weeks or until resolution (whichever occurs first). 
Participants with Grade 3 or 4 (symptomatic) left ventricular systolic dysfunction must 
interrupt treatment with belantamab mafodotin. Ejection fraction must be monitored 
every 4 weeks for a total of 16 weeks or until resolution. If recovery occurs (LVEF  
institutional LLN and symptom resolution) within 4 weeks, then treatment with 
belantamab mafodotin may be restarted at a reduced dose in consultation with the 
medical monitor. 
7.2.4. 
Corneal Event Stopping Criteria 
All belantamab mafodotin dose modifications and stopping criteria are to be based on the 
GS/KVA Scale for treatment related corneal toxicities (Appendix 9). Corneal events will 
be graded according to both CTCAE criteria for eye disorders (see Section 8.2) and the 
guidelines provided in Appendix 9. The treating physician or ophthalmologist (or 
optometrist, if an ophthalmologist is not available) must discuss the participants who 
develop a Grade 4 corneal event according to the GSK/KVA scale with the GSK Medical 
Monitor or a GSK ophthalmologist to determine whether the participant can be allowed 
to restart treatment with belantamab mafodotin or whether belantamab mafodotin should 
be permanently discontinued. The decision will be documented in study files, together 
with individual assessment of risk-benefit. For details on re-start guidance (Table 13). 
7.2.5. 
Infusion-Related Reaction Management and Stopping Criteria 
Premedication is not required prior to infusion unless deemed medically appropriate by 
the investigator following evaluation of infusion related reactions. Premedication should 
be considered in any participant who experienced an infusion related reaction at first or 
any subsequent infusion with belantamab mafodotin. 
IRRs should be managed by guidelines provided in Table 11. A participant that 
experiences a Grade 4 IRR should be permanently withdrawn from the study. 
7.2.6. 
Allergic and Anaphylactic Reaction Stopping Criteria 
All participants will be monitored carefully for evidence of allergic response. A 
participant that exhibits signs or symptoms of severe hypersensitivity or anaphylaxis will 
receive appropriate medical treatment and be permanently withdrawn from the study 
treatment.  

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7.3. 
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. 
• 
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. 
• 
Refer to the SOA for data to be collected at the time of study discontinuation 
follow-up and for any further evaluations that need to be completed. 
 
7.4. 
Lost to Follow Up 
The following actions must be taken in relation to a participant who fails to attend the 
clinic for a required study visit: 
• 
The site must attempt to contact the participant and re-schedule the missed visit 
as soon as possible.  
• 
The site must counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to 
continue or if the investigator believes that the participant should continue in the 
study.  
• 
In cases where the participant is deemed ‘lost to follow up’, the investigator or 
designee must make every effort to regain contact with the participant (where 
possible, 3 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, only then will he/she be 
considered to have withdrawn from the study with a primary reason of “Lost to 
Follow-up.”  
 
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 (Table 1).  
A list of clinical laboratory tests is displayed in Table 14. 
Whenever vital signs, and blood draws are scheduled for the same nominal time, it is 
recommended that the assessments occur in the following order: vital signs, followed by 

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the 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. 
• 
Study procedures and their timing are summarized in the SOA (Table 1 – Table 
3).  
• 
Protocol waivers or exemptions are not allowed.  
• 
Demographic and baseline assessments will include year of birth, sex, race, and 
ethnicity. 
• 
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. 
• 
Survival follow-up can be conducted by phone call.  
• 
Baseline disease assessments must be completed with 21 days prior to dosing 
start unless otherwise specified. Refer to SOA.  
• 
Screening assessments performed within the permitted time do not need to be 
repeated on C1D1 unless otherwise specified. 
• 
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. 
• 
ECHO must be completed within 35 days prior to first dose. 
• 
Imaging must be completed within 30 days prior to first dose. 
• 
On-study visits have a ±3-day window 
• 
PFS follow-up visits have a ±7-day window. 
• 
Survival follow-up visits have a ±14-day window. 
 

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Table 14 
List of Clinical Laboratory Tests 
Hematology1 
Platelet Count  
RBC Indices: 
Automated WBC 
Differential: 
Red blood cell (RBC) 
Count 
MCV 
Neutrophils 
White blood cell (WBC) 
Count (absolute)  
MCH 
Lymphocytes 
Reticulocyte Count 
MCHC 
Monocytes 
Hemoglobin 
 
Eosinophils 
Hematocrit 
 
Basophils 
Clinical Chemistry1 
Blood urea nitrogen (BUN) 
Potassium 
Aspartate aminotransferase 
(AST) 
Total and direct 
bilirubin 
Creatinine  
Chloride 
Alanine aminotransferase 
(ALT) 
Uric Acid 
Glucose 
Total bicarbonate 
Gamma glutamyl transferase 
(GGT) 
Albumin 
Sodium 
Calcium 
Alkaline phosphatase 
Total Protein 
Magnesium 
Phosphorous 
Creatine kinase (CK) 
LDH 
eGFR 
Spot urine (albumin / 
creatinine ratio)5, 8
 
 
Urine1 
Routine Urine Dipstick (Urinalysis required if blood or protein is detected by dipstick) 
Specific gravity 
pH, glucose, protein, blood and ketones by dipstick 
Microscopic examination (if blood or protein is abnormal) 
Other Safety 
C-reactive protein (CRP)1 
Troponin I5 
B-type natriuretic peptide (BNP)5 
Follicle stimulating hormone (FSH) and estradiol (as needed in women of non-child bearing potential only) 
(screening)1 
Pregnancy Test (urine or blood- per local practice)1 
Hepatitis B surface antigen (HBsAg)1 
Hepatitis B core antibody (HBcAb)1 
Hepatitis C (Hep C antibody)1: 
Note: Hep C RNA testing is optional but may be done to determine participant eligibility if Hep C antibody positive). 
Participants with positive Hepatitis C antibody due to prior resolved disease may be offered hepatitis C RNA testing 
to determine eligibility. 
 

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Table 14 
List of Clinical Laboratory Tests (cont.) 
PK/ADA  
Pharmacokinetics (PK)2, 3 
Anti-Drug Antibodies (ADA)2, 3 
Optional Testing 
PGx2 
Optional tissue sample at PD for BCMA (BM aspirate clot, or fresh tissue, or tissue block from 
extramedullary tumor)2 
Disease Evaluation Laboratory Tests 
Urine Protein 
Electrophoresis (UPEP)2 
urine 
Immunofixation2 
24-hour urine collection 
for M-protein2 
Calcium corrected for 
albumin (serum)
2 
Serum Protein 
Electrophoresis (SPEP)2 
Serum M-protein 
calculation 2 
Serum Immunofixation2 
Beta2 microglobulin2 
Serum Kappa, lambda 
free LC, FLC ratio2 
IgG, IgA, IgM,  
IgD4), IgE4)2 
  
 
Bone Marrow Aspiration/Biopsy 
Bone marrow for MRD testing2 
Bone marrow (aspirate preferred) for disease assessment1 
Bone marrow biopsy to confirm sCR by IHC1,7 
Bone marrow for FISH testing5,6  
Bone marrow aspirate for BCMA IHC assessment2  
Biomarker Measurements 
Soluble BCMA (sBCMA) 
(Serum)2 
cfDNA (plasma)2 
 
 
1. To be performed at local laboratory.  
2. To be performed at central laboratory.  
3. Not needed at screening 
4. Only for participants with IgD/E myeloma 
5. If not available from local laboratory, it can be performed at central laboratory. 
6. FISH testing at least for: t(4;14), t(14;16), 17p13del. BM samples from within 60 days prior to first dose are 
acceptable for FISH analysis. If not available from local laboratory, a bone marrow aspirate can be sent to central 
lab for analysis. If the participant is known to have high risk disease from previous FISH tests regardless of timing 
(i.e.: t(4;14), or t(14;16) they should be stratified as High Risk for the purpose of enrollment.  
7. Results from tests to confirm sCR will be collected and stored by third party vendor and reviewed by IRC. 
8. Obtained from first void 
 
8.1. 
Efficacy Assessments 
Standard disease assessments for RRMM will include the following assessments:  
• 
UPEP, Urine Immunofixation, 24 hr. collection for urine M-protein  
• 
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 LC, FLC ratio  

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• 
Bone marrow (aspirate preferred) at screening and to confirm CR. Additional 
BM testing for MRD testing in case of VGPR or CR is achieved, and BM biopsy 
for immunohistochemistry (IHC) to confirm sCR.  
• 
Imaging of extramedullary disease (in participants with extramedullary disease) 
• 
Germany: Only MRI is allowed to be used as imaging modality for 
participants with extramedullary disease. 
• 
PET/CT is required upon achieving CR or sCR  
• 
Germany: no PET/CT to confirm CR or sCR will be performed until approval 
by the German Federal Office for Radiation Protection until further notice.  
• 
Skeletal surveys at screening  
• 
Germany: Only MRI is allowed to be used as imaging modality of bones for 
lytic lesions. 
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 screening period 
(within 21 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 SRM. 
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 
must be performed as described in the SOA (Section 1.2).  
All assessments on study 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 IP due to PD the confirmation of laboratory 
parameters must be performed from a different blood collection performed either on the 
same day, or within 14 days of the original date of suspected disease progression, 
preferably before initiation of any new anti-myeloma therapy. For participants with PD 
due to extramedullary disease, confirmatory scans are not required. The laboratory 
parameters do not need to be repeated only if the extramedullary disease is the single site 
of progression. The assessments may be performed during End of Treatment Visit (Table 
3) for the Schedule of Activities of anti-cancer activity  
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 

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documented, a new disease assessment must be obtained at the time of discontinuation 
from study treatment. 
8.1.1. 
Independent Review Committee 
An Independent Review Committee (IRC) will be utilized to assess efficacy endpoints of 
the study. All laboratory parameters and lesion measurements used to assess participant 
response will be shared with the IRC. Additional information can be found in Appendix 3 
and in the IRC Charter.  
8.2. 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 4. 
Adverse events will be coded using the standard MedDRA and grouped by system organ 
class. Adverse events will be graded by the investigator according to the NCI-CTCAE, 
(version 4.03). Corneal events associated with belantamab mafodotin will also be graded 
according to the GSK/KVA scale provided in Appendix 9. Dose modifications as a result 
of corneal events will be based on the GSK/KVA scale for corneal events (Table 22).  
The investigator and any 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 treatment or the study, 
or that caused the participant to discontinue the study treatment (see Section 7). 
8.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information  
• 
All SAEs will be collected from the start of treatment until 45 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 (Table 1, Table 2, and 
Table 3). However, any SAEs assessed as related to study participation (e.g., study 
treatment, 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 45 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. 
• 
Medical occurrences that begin before the start of study treatment but after obtaining 
informed consent will be recorded on the Medical History/Current Medical 
Conditions section of the electronic case report form (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 Appendix 4. 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 in former study 
participants. However, if the investigator learns of any SAE, including a death, at 

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any time after a participant has been discharged from the study, and he/she considers 
the event to be reasonably related to the study treatment or study participation, the 
investigator must promptly notify the sponsor. 
• 
The method of recording, evaluating, and assessing causality of AEs and SAEs and 
the procedures for completing and transmitting SAE reports are provided in 
Appendix 4. 
• 
Investigator need not update tick-box in InForm to confirm review of the causality 
assessment for the SAE within 72 hours. It is enough to record the same in source 
notes. 
• 
For participants in the PACT phase of the study, GSK will continue to collect safety 
information including SAEs, AEs leading to treatment discontinuation, overdose, 
pregnancy cases and pre-specified ocular data via paper forms which will be reported 
directly to GSK (see SRM for details) for up to 70 days after last dose. Pre-specified 
ocular data will be reported until resolution unless the event is considered by the 
investigator to be unlikely to resolve, or the patient is lost to follow up. Additionally, 
any SAEs that are ongoing at the time of the final DCO must be followed up to 
resolution unless the event is considered by the investigator unlikely to resolve, or 
the patient is lost to follow-up. Updates to these events will also occur via paper 
forms directly to GSK (see SRM for details). GSK retains the right to request 
additional information for any patient with ongoing AE(s)/SAE(s) at EOS, if judged 
necessary. 
• 
Ocular FU: 
For participants continuing on belantamab mafodotin-containing study treatment as part 
of PACT:  
• 
Ocular exam schedule during PACT treatment: 
o Participants without ocular (including corneal) examinations findings, 
symptoms or vision changes when entering the PACT phase will be 
required to have an ocular assessment at least every 3 months, or more 
often as clinically indicated, until the end of treatment. 
o For participants who at the time of entering PACT have ocular (including 
corneal) examinations findings, symptoms or vision changes (or develop 
these during PACT treatment), the ocular assessment will occur (increase 
to) every 3 weeks (and prior to the next belantamab mafodotin infusion if 
dosing), until resolution (KVA Grade 1 or baseline). After resolution, the 
ocular exam assessment frequency may revert to at least every 3 months 
intervals, or as clinically indicated, until the end of treatment. 
• 
Ocular exam schedule after end of PACT treatment: 
o Participants with treatment-related ocular (including corneal) examination 
findings, symptoms, or vision changes at the end of PACT treatment will 
have ocular assessments at least every 3 months, or more often as 
clinically indicated, for up to 12 months from the end of treatment or until 
resolution (to KVA Grade 1 or baseline), or withdrawal of consent, 
whichever comes first. 

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o For participants without ocular (including corneal) examination findings, 
symptoms, or vision changes at the end of PACT treatment no further 
ocular exams are required. 
 
For participants who stopped belantamab mafodotin prior to PACT but have ongoing 
ocular events at the time of final study data-cut-off/start of PACT:  
• 
Participants with treatment-related ocular (including corneal) examination 
findings, symptoms, or vision changes at the start of PACT have ocular 
assessments at least every 3 months for up to 12 months from the end of 
treatment or until resolution (KVA Grade 1 or baseline), or withdrawal of 
consent, whichever comes first. 
 
8.2.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence.  
8.2.3. 
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 SAEs, and non-serious AEs of clinical 
interest, will be followed until the event is resolved, stabilized, otherwise explained, or 
the participant is lost to follow-up (as defined in Section 7.4). Further information on 
follow-up procedures is given in Appendix 4. 
8.2.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a study treatment 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 treatment 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 (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
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 Investigator’s Brochure and will notify the IRB/IEC, if 
appropriate according to local requirements. 

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8.2.5. 
Cardiovascular and Death Events 
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
For any cardiovascular events detailed in Appendix 4 and all deaths, whether or not they 
are considered SAEs, 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 must be recorded in the specific cardiovascular section of the 
eCRF within one week of receipt of a CV Event data query prompting its completion. 
8.2.6. 
Disease-Related Events and/or Disease-Related  
Disease progression does not need to be reported as a serious adverse event (SAE). Death 
due to disease under study is to be recorded on the Death electronic case report form 
(eCRF). However, if the underlying disease (i.e., progression) is greater than that which 
would normally be expected for the participant, or if the investigator considers that there 
was a causal relationship between treatment with study treatment(s) or protocol design or 
procedures and the disease progression, then this must be reported as a SAE. 
8.2.7. 
Adverse Events of Special Interest 
Adverse events of special interest (AESI) for belantamab mafodotin are corneal events, 
thrombocytopenia and infusion related reactions. The severity of all AESI will be graded 
utilizing the National Cancer Institute- Common Toxicity Criteria for Adverse Events. 
Severity of corneal events will also be graded using the GSK/KVA scale for corneal 
events provided in Table 22. Guidelines for dose modifications and interruptions for 
management of common toxicities associated with the study treatment(s) are provided in 
Table 11. Dose modifications for belantamab mafodotin corneal events will be based on 
the GSK/KVA scale for corneal events in Table 22. 
8.2.8. 
Pregnancy 
Do not collect pregnancy information for female participants known to be pregnant 
during the screening phase or before exposure to study. 
The need for a screening pregnancy test depends on whether a female participant is of 
childbearing potential or non-childbearing potential. 
If a female participant is of childbearing potential, she must have a serum β-human 
chorionic gonadotropin (β –HCG) pregnancy test performed within 72 hours prior to the 
first dose of study treatment. Participants with positive pregnancy test result must be 
excluded from the study. Participants with negative pregnancy test result must agree to 
use an effective contraception method as described below during the study until 4 months 
following the last dose of study treatment. 

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• 
Details of all pregnancies for female partners of male participants will be collected 
after the start of study treatment to 6 months following last dose of study treatment.  
• 
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 Appendix 5. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, and ectopic pregnancy) are considered SAE. 
8.2.9. 
Ocular Examinations and Procedures 
A full baseline ophthalmic examination for all participants must include, but is not 
limited to: 
1. Best corrected visual acuity  
2. Documentation of manifest refraction used to obtain best corrected visual acuity 
3. Current glasses prescription (if applicable) 
4. Pupillary exam 
5. Extraocular muscle movements (graded from one to four with (+) sign 
indicating over action, (-) sign indicating under action and 0 representing normal 
movements 
6. Tear film examination: Schirmer’s test with anesthesia and tear breakup time  
7. Intraocular pressure measurement & time checked 
8. Full anterior segment examination including fluorescein staining of the cornea: 
9. Anterior segment exam (slit lamp) includes: orbit/lids/adnexa, conjunctiva, 
sclera, cornea, anterior chamber, iris, lens and anterior vitreous 
10. Anterior segment photography of a fluorescein stained cornea 
11. Dilated funduscopic exam: fundus photography with interpretation. 
12. Pachymetry  
The on treatment and follow-up ophthalmic exam must include everything except: dilated 
funduscopic exam /, including fundus photography, anterior segment photography, 
extraocular muscle movements, (which must be performed as clinically indicated) and 
current glasses prescription (if applicable). The last follow-up ophthalmic visit should 
also include anterior segment photography of a fluorescein stained cornea. Representative 
images will be collected and maintained at the investigator site as source data. 
The end of study treatment visit ophthalmic exam should match the baseline (screening) 
exam. 
Additional examinations should be performed at the discretion of the treating eye 
specialist.  
 

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8.2.10. 
Ocular Sub-Study Examinations 
Refer to Table 4 for the schedule of assessments for ocular sub-study of participants 
Although ocular corticosteroids have been used in both published studies (Tannir, 2014; 
Moskowitz, 2015; Thompson, 2015; Reardon, 2016; Macsai, 2016) and BMA117159 to 
ameliorate the frequency and severity of MMAF-associated corneal events, this has yet to 
be investigated systematically. Furthermore, the effect of MMAF-conjugated ADCs on 
the eye has not been fully delineated in studies to date. Therefore, Study 205678 will 
include a sub-study of approximately 30 participants (~15 participants each dose) to 
evaluate the effect of ophthalmic topical corticosteroids on belantamab mafodotin-
associated corneal findings and to further characterize these findings. This sub-study of 
participants will be recruited at selected investigational sites associated with 
ophthalmologists with subspecialty training/expertise in the cornea. These participants 
will undergo additional ophthalmic examinations during the first 4 cycles of treatment at 
a minimum or as clinically indicated as determined by the treating ophthalmologist. A 
separate informed consent (in addition to the main study ICF) will be obtained from these 
participants. 
8.2.10.1. 
Monocular prophylaxis 
Figure 4 summarizes the prophylaxis administration schedule in the ocular sub-study of 
participants. 
The treating ophthalmologist, but not the participant, will be blinded as to which eye has 
received the prophylactic steroid treatment. 
Randomization will be done within each treatment arm centrally using a randomization 
schedule, which will assign participants in a 1:1 ratio to: 
• 
receive topical corticosteroids in right eye only 
• 
receive topical corticosteroids in left eye only. 
The participants of the sub-study will administer prophylactic corticosteroid eye drops 
(prednisolone acetate 1%, prednisolone phosphate 1%, dexamethasone 0.1%, or 
equivalent, 1 drop four times daily starting one day prior to dosing for a total of 7 days). 
They will be instructed to administer the steroid drops in only one eye. *** Based on data 
from the primary analysis the use of prophylactic steroid eye drops is no longer required 
for the main study participants. Determination for use of steroid eye drops will be up to 
the discretion of the treating ophthalmologist for the ocular sub-study participants.  
Corticosteroid treated eye 
• Participant should administer 1 drop of topical corticosteroid followed by 1 drop of 
preservative-free artificial tears 5-10 minutes later, four times daily. This should start 
one day prior to dosing for a total of 7 days.  

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Other Eye 
• Participants should administer 1 drop of preservative-free artificial tears followed by 
another 1 drop of preservative-free artificial tears 5-10 minutes later, 4-8 times daily. 
This should start one day prior to dosing for a total of 7 days. Outside the 7-day 
prophylaxis period, preservative-free artificial tears should be administered in each 
eye at least 4-8 times daily as needed (See Appendix 9, Section 11.9). 
Figure 4 
Ocular prophylaxis schematic 
 
***Based on data from the primary analysis the use of prophylactic steroid eye drops is no longer required for the main 
study participants. Determination for use of steroid eye drops will be up to the discretion of the treating ophthalmologist 
for the ocular sub-study participants.  
8.2.10.2. 
Monocular treatment 
If a participant in the ocular sub-study develops a corneal event outside the 7-day 
prophylaxis period, steroid eye drops may be restarted in only one eye at the discretion of 
the treating ophthalmologist. If steroid treatment is started in only one eye refer to Table 
13 and treat the contralateral eye with an equal number of preservative-free artificial 
tears. 
Alternatively, the treating ophthalmologist may start topical corticosteroid treatment in 
both eyes at any time if clinically indicated and beneficial to the participant (Table 13). If 
such decision is made at any time between treatment cycles 1 to 4, the participant will 
receive further prophylaxis and treatment as any other participant on the study according 
to Section 8.2.9 but will continue to undergo additional imaging as described below. 
The treating ophthalmologist may unblind themselves at any time if they believe it to be 
in the best interest of the participant. This may be done by asking the clinical site staff. 
Topical 
Corticosteroids QID
Preservative Free 
Artificial Tears QID
Preservative Free 
Artificial Tears QID
Preservative Free 
Artificial Tears QID
Drops 
Matched in 
Frequency
Wait 5 minutes
Wait 5 minutes
Prophylaxis
Randomization: Right/Left Eye
Next Dosing

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After Cycle 4, monocular steroid treatment will be performed at the discretion of the 
treating ophthalmologist 
Based on data from the primary analysis the use of prophylactic steroid eye drops is no 
longer required for the main study participants. Determination for use of steroid eye 
drops will be up to the discretion of the treating ophthalmologist for the ocular sub-study 
participants.  
8.2.10.3. 
Sub-Study Exams 
Participants will be assessed by the treating ophthalmologist at baseline, every 3 weeks or 
prior to each dose, and on Day 10 of Cycles 1, 2, 3, and 4. After Cycle 4, the Day 10 
exam may be omitted.  
In addition to the full ophthalmic exam (Section 8.2.9), the participants at these selected 
sites will undergo the following additional studies during screening (baseline), at the first 
instance of corneal changes attributable to belantamab mafodotin, end of study treatment 
visit, last follow-up visit and as clinically indicated by the treating ophthalmologist:  
1. Anterior segment OCT (optical coherence tomography)  
2. Anterior segment/corneal slit lamp photography  
3. 
Confocal microscopy (if available at the site) 
4. 
Lissamine green staining 
 
Given that these evaluations are exploratory, the treating ophthalmologist has the 
discretion to perform them more frequently as they believe appropriate for the optimal 
care of the individual participant. Representative images will be collected and maintained 
at the investigator site as source data. 
8.3. 
Treatment of Overdose 
There is no specific antidote for an overdose of belantamab mafodotin. 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 
they have resolved and belantamab mafodotin concentrations are predicted to be 
within the anticipated range in absence of the overdose. 
8.4. 
Safety Assessments 
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8.4.1. 
Physical Examinations 
At screening, on dosing days, and at end of study treatment visit a full physical 
examination will include assessments of the head, eyes, ears, nose, throat, skin, thyroid, 
lungs, cardiovascular, abdomen (liver and spleen), lymph nodes, and extremities. Height 
(once at screening only) and weight must also be measured and recorded. 
8.4.2. 
ECOG Performance Status 
Participant performance status will be assessed at Screening, every 3 weeks starting at 
Week 4 and End of Treatment using the Eastern Cooperative Oncology Group (ECOG) 
scale, provided in Appendix 8. 
8.4.3. 
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 signs are measured multiple times, temperature does not 
need to be repeated unless clinically indicated. 
8.4.3.1. 
First Infusion 
Monitoring intervals: Vital signs must be monitored at designated time points related to 
drug infusion as specified in the Schedule of Activities (Section 1.2). In general, 
participants must also be monitored for at least 1 hour after the completion of the first 
infusion and may be discharged if considered clinically stable and all other study 
procedures have been completed.  
8.4.3.2. 
Subsequent Infusions 
Monitoring intervals: Vital signs must be monitored at designated time points related to 
drug infusion as specified in the Schedule of Activities (Section 1.2). Participants may be 
discharged after the infusion has been completed if considered clinically stable and all 
other study procedures have been completed.  
8.4.4. 
Echocardiogram 
Echocardiograms (ECHOs) must be performed at baseline to assess cardiac ejection 
fraction for the purpose of study eligibility, as specified in the SOA. The evaluation of 
the echocardiographer must include an evaluation for left ventricular ejection fraction 
(LVEF). If an ECHO is performed on study the results must be documented in the e-
CRF. 
8.4.5. 
Laboratory Assessments 
All protocol-required laboratory assessments, as defined in Table 14, must be performed 
according to the SOA (Section 1.2). Details for the preparation and shipment of samples 
for central laboratory assessments will be provided in the SRM. 

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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 CRF. 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 within 45 days after the last dose of study treatment must be repeated until the 
values return to normal or baseline.  
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. 
Hematology, clinical chemistry, urinalysis, and additional parameters to be tested are 
listed, with detailed instructions and timing, in the SRM. 
8.4.6. 
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 
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 sub-study of items selected from the PRO-CTCAE 
Version 1.0 Item library will be administered. Participants who are not able to complete 
the questionnaire on their own and require assistance may have the interview conducted 
verbally or by telephone. The interview must be read to the participants verbatim, and 
participant responses must be recorded directly without any interpretation.  
The PRO-CTCAE will be administered to participants in different regions based on the 
availability of translated versions.  
 
8.4.7. 
Visual Function Questionnaires 
The impact of potential ocular toxicity on function and health-related quality-of-life will 
be assessed with the use of two visual function questionnaires, the NEI-VFQ-25 and 
OSDI. All participants will use the Self-Administered version of the 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 must use an Interviewer Administered format. If the Interviewer Administered 
format is being used, it must be read to the participants verbatim, and participant 
responses must be recorded directly without any interpretation. For any additional 

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assessments conducted via telephone (either during participation in the treatment period 
or during Follow-up), the Interviewer Administered format must be used.  
The NEI-VFQ-25 and OSDI will be administered to participants in different regions 
based on the availability of translated versions. 
8.4.7.1. 
National Eye Institute Visual Function Questionnaire-25 
The NEI-VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 
vision-related constructs, plus an additional single-item general health rating question 
[Orr, 2011; Kirwan, 2012; Mangione, 2001]. These include a global vision rating (1 
item); difficulty with near vision activities (3 items); difficulty with distance vision 
activities (3 items); limitations in social functioning due to vision (2 items); role 
limitations due to vision (2 items); dependency on others due to vision (3 items); mental 
health symptoms due to vision (4 items); driving difficulties (3 items); limitations with 
peripheral vision (1 item), limitations with color vision (1 item); and Ocular pain (2 
items). In addition to the core items from the NEI-VFS-25, select questions from the 
Appendix of Optional Additional Questions will also be administered to further assess the 
impact of ocular toxicity on visual function. 
8.4.7.2. 
The Ocular Surface Disease Index 
The Ocular Surface Disease Index (OSDI) is a 12-item questionnaire designed to assess 
both the frequency of dry eye symptoms and their impact on vision-related functioning 
[Schiffman, 2000; Dougherty, 2011]. 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. 
8.5. 
Pharmacokinetics 
8.5.1. 
Blood Sample Collection for Pharmacokinetics 
Blood samples for pharmacokinetic (PK) analysis of belantamab mafodotin (ADC and 
total antibody) and cys-mcMMAF will be collected at the time points indicated in the 
Schedule of Activities table (Section 1.2). Each PK sample must be collected as close as 
possible to the planned time relative to the dose (which is 0 h) administered to the 
participant on PK days. The actual date and time of each blood sample collection will be 
recorded. All PK, sBCMA, and ADA samples once collected (regardless of dosing) may 
be analyzed if the sample date and time have been recorded. 
Details on PK blood sample collection, processing, storage, and shipping procedures are 
provided in the SRM. 
8.5.2. 
Pharmacokinetic Sample Analysis 
Plasma analysis will be performed under the control of GSK Platform Technology and 
Sciences (PTS)-Bioanalysis Immunogenicity and Biomarkers (BIB) group, the details of 
which will be included in the SRM. Concentrations of belantamab mafodotin (ADC and 

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total 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 SRM). 
Once the plasma has been analyzed for belantamab mafodotin (ADC and total antibody) 
and cys-mcMMAF, any remaining plasma may be analyzed for other compound-related 
metabolites and the results reported under a separate GSK PTS-BIB protocol. 
8.6. 
Immunogenicity  
Serum samples for the analysis of anti-belantamab mafodotin antibodies will be collected 
from all participants according to the SoA. Additionally, serum samples should be 
collected at the final visit from participants who discontinued study intervention or were 
withdrawn from the study. These samples will be tested by the sponsor or sponsor’s 
designee.  
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 belantamab mafodotin. Additionally, plasma 
samples will be collected at the same time points (see SoA) as the immunogenicity 
samples and analyzed to determine the belantamab mafodotin and total monoclonal 
antibody plasma concentrations. The plasma concentration results will enable 
interpretation of the anti-drug antibody data. Anti-drug antibody samples will be disposed 
of three months after final approved results are provided to the Clinical Study Team or its 
designee or upon documented study termination. 
Details of sample preparation, storage, and analysis will be provided in the SRM.  
8.7. 
Translational Research 
See Section 8.9. 
8.8. 
Genetics 
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. Separate consent signature is required for 
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Information regarding genetic research is included in Appendix 6. In approving the 
clinical protocol, the IEC/IRB and, where required, the applicable regulatory agency, are 
also approving the genetic research described in Appendix 6 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 
for genetic assessments, can be initiated. If genetic assessments are not approved, they 
will not be conducted. 
8.9. 
Tumor Biomarker Analysis 
8.9.1. 
sBCMA Sample Analysis 
The BCMA receptor undergoes gamma-secretase mediated cleavage, leading to release 
of the BCMA extracellular domain as soluble BCMA (sBCMA) into the circulation 
[Laurent, 2015]. 
Samples will be collected to measure concentrations of sBCMA at the time points 
specified in the SOA using a validated assay. Details of sample preparation, storage, and 
analysis will be provided in the SRM.  
Serum analysis for sBCMA will be performed under control of GSK PTS-BIB group, the 
details of which will be included in the SRM. Raw data will be archived at the 
bioanalytical site (detailed in the SRM). 
8.9.2. 
Potential Tumor Related Biomarkers 
While BCMA expression is present in multiple myeloma, there is some variability in its 
expression, as well as its membranous/cytosolic expression pattern. Therefore, it is 
important to determine if there is any association between the expression levels of 
BCMA on multiple myeloma cells and clinical responses.  
Additionally, any blood, serum, 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. 
Samples will be collected at the time points indicated in the SOA. 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. Additionally, novel biomarkers may also be incorporated, as data warrants. 
These analyses may include but not be limited to: 
• 
Bone marrow BCMA expression by IHC performed on bone marrow aspirate 
• 
Measurements of the serum levels of soluble BCMA (sBCMA)  

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• 
Soluble factors, including circulating plasma cell-free DNA (cfDNA). 
 
8.10. 
Evaluation of Anti-Cancer Activity 
Response will be assessed according to the IMWG criteria, [Kumar, 2016] by the 
Investigator and by an IRC. 
Standard disease assessments for MM will include serum and urine laboratory tests, bone 
marrow biopsy at the time of CR (IHC), and MRD testing at the time of VGPR, CR, and 
baseline. Evaluation will follow the guidance of International Myeloma Working Group 
(IMWG) Uniform Response Criteria for Multiple Myeloma 2016. 
• 
Clinical efficacy measured as Overall Response Rate (ORR), which is defined as the 
percentage of participants with confirmed stringent complete response (sCR), 
complete response (CR), very good partial response (VGPR), or partial response 
(PR) as assessed by 2016 recommendation of the IMWG Panel I [Kumar, 2016].  
• 
Other efficacy measures of interest (see Section 8.1)  
• 
The percentage of participants achieving MRD negativity. 
Disease assessment will include laboratory testing and physical examination (as indicated 
for palpable/superficial lesions), or imaging CT, MRI, PET CT, or X-ray (as indicated). 
Laboratory-based disease assessments will be completed within 21 days prior to the first 
dose of belantamab mafodotin then testing will be performed every 3 weeks from Cycle 1 
Day 1 (C1D1). The imaging will be performed up to 30 days prior to the first dose and 
will be repeated as indicated in the SOA table. See the SOA for the Schedule of 
Activities of anti-cancer activity.  
Assessments must be performed on a calendar schedule and must not be affected by dose 
interruptions/delays.  
MRD negativity rate (defined as the percentage of participants who are MRD negative by 
clonoSEQ). Testing will be performed at: Screen for all participants; and at the time of 
achieving VGPR or CR. The testing will be repeated 6 months and 12 months after 
achieving VGPR or CR. If MRD sample is drawn after date of achieving VGPR or CR 
the repeat testing should take place 6 months and 12 months from time of initial MRD 
testing  
8.11. 
Health-Related Quality-of-Life 
Three Health-Related Quality-of-Life (HRQoL) assessments will be performed in this 
study. More details about all patient questionnaires can be found in the SRM.  
The following assessments will be administered to participants in different regions based 
on the availability of translated versions. 

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8.11.1. 
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 five functional scales (Physical, Role, 
Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and 
Nausea/Vomiting), a Global Health Status/QoL scale, and six 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]. 
8.11.2. 
European Organization for Research and Treatment of Cancer 
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]. The module comprises 20 
questions that address four myeloma-specific HRQoL domains: Disease Symptoms, Side 
Effects of Treatment, Future Perspective, and Body Image. Three of the four QLQ-MY20 
domains are multi-item scales: Disease Symptoms (includes bone aches or pain, back 
pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity); Side 
Effects of Treatment (includes drowsiness, thirst, feeling ill, dry mouth, hair loss, upset 
by hair loss, tingling hands or feet, restlessness/agitation, acid indigestion/heartburn, and 
burning or sore eyes); and Future Perspective (includes worry about death and health in 
the future, and thinking about illness). The Body Image scale is a single-item scale that 
addresses physical attractiveness. 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 and Side Effects of Treatment represents a high level of 
symptomatology or problems, whereas a high score for Future Perspective and Body 
Image represents better outcomes [Proskorovsky, 2014]. 
8.11.3. 
Qualitative Telephone Interviews (Patient Interviews) 
To further evaluate disease and treatment related symptoms and associated impacts on 
function and health-related quality of life, participants will participate in qualitative 
interviews conducted via telephone. The interview will be conducted by a trained 
interviewer in the participant’s native language and will be audio recorded for 
transcription and analysis. 
The patient interview (PRO) should be conducted via telephone within 21(7 days) days 
following Day 1 of the fourth treatment cycle (C4D1). The PRO interview should also be 
conducted within 21 days (7 days) of the participants end of treatment visit, unless the 
participant has already completed their interview following C4D1 within the prior 30 
days. 

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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Hypothesis Testing 
This is a two-arm study. The primary objective of this study is to establish the efficacy of 
BCMA over historical control with respect to ORR for participants with RRMM for each 
of the two dose levels (frozen liquid solution) studied. 
The study is designed to provide evidence with respect to ORR to either support the null 
hypothesis, H0: ORR ≤15%, or reject H0 in favor of the alternative hypothesis, 
H1: ORR≥33%. The hypothesis testing will be performed within each arm separately. No 
hypothesis testing for comparing ORR between the two arms will be performed. 
All randomized participants will be included in the final analysis to test the hypotheses of 
interest regardless of length of follow-up or whether or not they receive the treatment or 
whether or not they have a post-baseline assessment (i.e., participants will not be 
replaced). 
An interim analysis (IA) will be conducted after approximately 25 randomized 
participants per arm are evaluable (i.e., received at least two doses of study treatment and 
have completed at least one disease assessment after the second dose, or progressed or 
died or discontinued treatment due to reasons other than PD).  
The Final analysis will be performed based on a data cutoff 6 months after the last 
participant (in the frozen liquid solution) is randomized in the study to allow sufficient 
data maturity of all efficacy endpoints. Time from first-subject-first visit (FSFV) to 
primary ORR analysis will be approximately 12 months. The timeline is subject to 
change based on the actual enrollment rate. 
An updated analysis for OS will be performed at end of study as defined in Section 4.3. 
9.2. 
Sample Size Determination 
The sample size calculation was initially performed using East 6.4 software as a starting 
point, based on the ORR comparison between the belantamab mafodotin arm and the 
historical control in order to choose a final refined study design. The following 
assumptions were made in the estimation of the required sample size: 
• 
Normal approximation of binomial proportion 
• 
A response rate of ≥33% in the BCMA arm and ≤15% for the historical control 
• 
A 1.25%, one-sided risk of erroneously claiming superiority of the BCMA arm, in 
the presence of no true underlying improvement 
• 
A ~90% chance of rejecting the null hypothesis when the alternative hypothesis is 
true 
An IA after approximately 38% of information is available (i.e., approximately after 25 
participants out of originally planned 65 participants per arm are evaluable for IA), with a 
futility rule based on a gamma spending function. 

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The operating characteristics were refined using simulation to account for both within 
arm futility rule and the comparative futility rule. Based on the simulation results with the 
originally planned sample size of 65 participants per arm, there is 86.90% power to reject 
the null hypothesis within each arm with a 1-sided type I error of 1.23%. 
Due to over enrollment, it is estimated that approximately 200 participants (~100 per 
arm) will be randomized to the frozen liquid solution. At the Final analysis, the null 
hypothesis will be rejected if the lower bound of 2-sided 97.5% exact C.I. exceeds the 
historical control rate of 15%.  
With no change to planned IA (i.e., approximately after 25 participants/arm are evaluable 
for IA, and same futility boundary), simulation results show that there is 92.38% power 
to reject the null hypothesis within each arm with a 1-sided type I error of 0.97% for 100 
participants per arm as specified in Section 9.3 and Section 9.5. 
The study will also include an independent cohort of approximately 25 additional 
participants who will receive the lyophilized configuration of belantamab mafodotin. The 
sample size for this cohort was chosen based on feasibility in order to gain clinical 
experience with the lyophilized configuration. The probability of observing a >=20% RR 
was retrospectively calculated. If the true RR is 33% there is a 95% probability of 
observing at least a 20% RR with 25 participants. This cohort will be analyzed separately 
from participants enrolled to the frozen liquid solution formulation.  
9.3. 
Sample Size Sensitivity 
Table 15 shows the various power scenarios at the final ORR analysis under different 
assumption of the ORR given the sample size of 65, and 100 participants per arm and 
stopping rules based on group sequential design as specified in Section 9.5.9.1. 
Table 15 
Statistical Power Scenarios 
ORR 
Number of 
Participants per 
arm  
Power (%) 
BCMA 
Monotherapy (%) 
Historical Data (%) 
40 
15 
65 
96.05 
35 
15 
65 
91.52 
30 
15 
65 
75.13 
25 
15 
65 
43.18 
20 
15 
65 
12.81 
40 
15 
100 
96.50 
35 
15 
100 
94.62 
30 
15 
100 
85.08 
25 
15 
100 
55.21 
20 
15 
100 
15.92 
Note: The power for each arm is calculated based on 10,000,000 simulations using R, assuming both arms have the 
same assumptions of ORR 

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9.4. 
Populations for Analysis 
Six specific populations have been defined for this study, as shown in Table 16. 
Table 16 
Analysis Populations Defined for the Study 
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. 
Efficacy  
Efficacy population will consist of first 130 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 used for sensitivity analysis of primary and selected 
secondary efficacy endpoints. 
Safety 
 
The Safety population will consist of all participants who receive at least 1 dose of study 
treatment. This population will be used for the analysis of clinical safety data  
Evaluable 
The Evaluable Population will consist of all participants who have at least two doses of study 
treatment and have completed at least one disease assessment after the second dose. This 
population will be the primary population for summarizing ORR to compare with stopping 
boundaries in interim analysis only. Refer to IDMC charter for more details.  
Pharmacokinetic 
The Pharmacokinetic Population will consist of those participants in Safety Population from 
whom at least one PK sample has been obtained and analyzed. This population will be the 
primary population for PK analyses. 
 
9.5. 
Statistical Analyses 
Statistical analyses (both interim and final) will be performed by the sponsor or under the 
authority of the sponsor. A general description of the statistical methods to be used to 
analyze the efficacy and safety data is outlined below. Specific details will be provided in 
the RAP.  
9.5.1. 
Efficacy Analyses 
Primary analysis of the primary endpoint ORR will be based on the responses assessed by 
the Independent Review Committee (IRC). Investigator-assessed ORR will also be 
reported. Analysis of secondary endpoints will include TTR, DoR, TTP, and PFS as 
assessed by both investigator and IRC.  
Primary analysis for all efficacy endpoints will be based on the ITT population. 
In addition, sensitivity analysis for ORR, DoR, and TTR as assessed by both investigator 
and IRC will be performed using efficacy population; other endpoint-specific sensitivity 
analyses will be described in the RAP. At interim analysis, investigator-assessed ORR 
will be analyzed based on the Evaluable Population. In case that one dose arm is dropped 
based on interim analysis (IA), and some participants in that arm switch to the remaining 
dose arm, a sensitivity analysis of ORR based on participants who did not switch may be 
performed. 

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Appropriate subgroup analyses may be performed if data permits, e.g. the primary 
endpoint ORR may be analyzed by age (<65 years, >=65 years), gender (Female, Male), 
ethnicity (Hispanic, non-Hispanic) and race groups (American Indian or Alaskan Native, 
Asian, Black, Native Hawaiian or Other Pacific Islander, White, Mixed Race), prior anti-
cancer therapy and other baseline characteristics. The estimates along with 95% exact 
confidence interval (CI) will be provided. In subgroup analyses, no hypothesis testing 
will be performed. 
The analytical methods planned for each endpoint are described in Table 17. 
Table 17 
Statistical Analysis Methods for Efficacy Endpoints 
Endpoint 
Statistical Analysis Methods 
Primary 
Overall Response Rate is the primary endpoint of this study; it is defined as the percentage of 
participants with a confirmed PR or better (i.e., PR, VGPR, CR and sCR), according to the 
IMWG Response Criteria [Kumar, 2016]. 
The number and percentage of participants in the following response categories will be 
presented sCR, CR, VGPR, PR, MR, SD, PD, and NE 
sCR+CR+VGPR+PR for ORR 
The corresponding 97.5% exact CI for ORR will also be provided. Participants with unknown or 
missing response will be treated as non-responders, i.e., these participants will be included in 
the denominator when calculating percentages of response. 
The null hypothesis related to ORR against a historical control will be tested by comparing the 
number of responders with the pre-specified stopping boundaries in the ITT and efficacy 
population. The boundaries will be adjusted as needed based on the final sample size. 
ORR will be analyzed at interim and final analysis. A participant with best confirmed response 
of PR or better will be considered as a responder. 
ORR at final analysis will be based on the confirmed responses from IRC assessment in both 
ITT and Efficacy population. In addition, ORR based on confirmed response from investigator 
assessment will be performed in both ITT and Efficacy population.  
ORR at IA will be analyzed based on investigator-assessed confirmed responses if available. 
However, in case a participant has achieved a response of PR or better at data cut, which was 
not confirmed due to the time constraints (too short timeframe for the next assessment) but with 
a potential to be confirmed through subsequent assessments after interim, the participant will 
also be considered as a responder. More details will be provided in the RAP. 
Secondary 
Secondary efficacy endpoints of this study are CBR, DoR, TTR, PFS, TTP, and OS. 
CBR, TTR, and DoR as assessed by IRC and investigator will be analyzed using both ITT and 
Efficacy population. Other TTE endpoints will be analyzed using ITT population only.  
CBR is defined as the percentage of participants with a confirmed minimal response (MR) or 
better, according to the IMWG Response Criteria [Kumar, 2016]. CBR at interim and final will be 
summarized in the same way as the primary endpoint ORR. No hypothesis testing will be 
performed for CBR 
DoR is defined as the time from first documented evidence of PR or better until the earliest date 
of disease progression (PD) per IMWG, or death due to PD among participants who achieve a 
response (i.e., confirmed PR or better). Responders without disease progression will be 
censored at the censoring time point for TTP.  
DoR will be analyzed at the time of final ORR analysis. 

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Endpoint 
Statistical Analysis Methods 
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).  
TTR will be analyzed at the time of final ORR analysis. 
PFS is defined as the time from randomization until the earliest date of PD per IMWG, or death 
due to any cause. Determination of dates of PFS event and dates for censoring will be 
described in the RAP.  
PFS will be analyzed at the time of final ORR analysis, also at study close out if applicable. 
TTP is defined as the time from randomization until the earliest date of PD per IMWG, or death 
due to PD. Determination of dates of TTP event and dates for censoring will be described in the 
RAP.  
TTP will be analyzed at the time of final ORR analysis, also at study close out if applicable. 
OS is defined as the time from randomization until death due to any cause. Participants who 
withdraw consent from the study or are lost to follow-up will be censored at the time of 
withdrawal or lost to follow-up. Participants who are still alive at the clinical cut-off date for the 
analysis will be censored at the last known alive date or last contact date. The last contact date 
will be determined by the maximum collection/assessment date from among selected data 
domains within the clinical database. OS, including 12- and 18-month survival rates, will be 
analyzed for the safety population.  
An OS analysis will be performed at the time of final ORR analysis if there is a sufficient number 
of death events. An updated OS analysis will be performed at the end of study as defined in 
Sec 5.3 of the protocol. 
For all the TTE endpoints described above, median TTE with 95% CI will be estimated 
employing the Kaplan-Meier method. A Kaplan-Meier survival curve will be generated. The 
number and percentage of participants who had the event or were censored will also be 
reported. In addition, the survival rate with 95% CI at 
12 and 18 months will be estimated using Kaplan-Meier methods for the OS endpoint. 
Exploratory 
MRD negative rate is defined as the proportion of participants who are negative for MRD at any 
time point after first dose as determined by the protocol defined testing procedure. For analysis 
purposes, participants in the safety population without MRD assessment will be considered as 
having positive MRD. 
 
The MRD negative rate will be calculated based on the ITT population. The corresponding 95% 
exact CI will be provided. 
Other exploratory endpoints will be described in the reporting and analysis plan (RAP) 
CBR: clinical benefit rate; CI: confidence interval; CR: complete response; DoR: duration of response; Minimal 
Response MR; SD: stable disease; MRD: Minimal Residual Disease; NE: non-evaluable; ORR: overall response rate; 
OS: overall survival; PD: progressive disease; PFS: progression-free survival; PR: partial response; RAP: report 
analysis plan; sCR: stringent complete response; TTP: time-to-progression; TTR: time-to-response; VGPR: very good 
partial response. 
 
9.5.2. 
Safety Analyses 
All safety analyses (Table 18) will be performed on the Safety Population.  

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Table 18 
Statistical Analysis Methods for Safety Endpoints 
Endpoint 
Statistical Analysis Methods 
Secondary 
Adverse Events: All adverse events whether serious or non-serious, will be reported from the 
start of treatment until 45 days after the last dose of study treatment, until the participant 
withdraws consent for study participation, or until the participant starts subsequent anticancer 
therapy, whichever occurs first. AEs will be recorded using standard medical terminology and 
graded according to the NCI-CTCAE, Version 4.03. For AE reporting, the verbatim term used in 
the CRF 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, treatment-related 
AEs, SAEs, and AEs leading to discontinuation of study treatment. Adverse events, if listed in 
the NCI-CTCAE (version 4.03,) will be summarized by the maximum grade.  
 
Characteristics (e.g., number of occurrences, action taken, grade, etc.) of the following AEs 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, and range) will be used to 
summarize observed laboratory values and change from baseline in observed value 
at each scheduled visit or worst-case post baseline, as appropriate. 
• 
The worst-case- toxicity grade in hematology and chemistry result during the 
treatment will be summarized. 
• 
Corneal events associated with belantamab mafodotin will be summarized using the 
GSK/KVA scale 
 
Other Safety Measures: Data for vital signs, electrocardiograms (ECGs), echocardiograms 
(ECHOs), 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. Further details will be provided in the Reporting and Analysis Plan (RAP). 
Exploratory 
Exploratory analyses will be described in the RAP 
 
9.5.3. 
Analyses of Health-Related Quality of Life Data 
Descriptive statistics will be used to summarize scores derived from different 
questionnaires and change from baseline at each scheduled visit. Additional details will 
be provided in the reporting and analysis plan. 
9.5.4. 
Pharmacokinetic Analyses 
9.5.4.1. 
Pharmacokinetic Data Analyses 
Concentration-Time Data: Linear and semi-logarithmic individual concentration-time 
profiles and mean and median profiles (when appropriate) will be plotted for belantamab 
mafodotin (ADC and total mAb) and cys-mcMMAF. Concentrations of belantamab 
mafodotin (ADC and total mAb) and cys-mcMMAF will be listed for each participant 
and summarized (when appropriate) by planned time point and dose level. 

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Derived Pharmacokinetic Parameters: Pharmacokinetic analyses will be the 
responsibility of Clinical Pharmacokinetics/Modelling and Simulation, GSK.  
Plasma belantamab mafodotin (ADC, total mAb) and cys-mcMMAF concentration-time 
data will be analyzed by non-compartmental methods using WinNonlin. Calculations will 
be based on the actual sampling times recorded during the study. From the plasma 
concentration-time data, the following PK parameters will be determined for belantamab 
mafodotin (ADC and total mAb) as data permit, for each participant after each dose of 
belantamab mafodotin:  
• 
maximum observed plasma concentration (Cmax), time to Cmax (tmax), predose 
plasma concentration (Ctrough) 
• 
For Cycle 1 and Cycle 3: area under the plasma concentration-time curve [AUC(0-t), 
AUC (0-tau) and/or AUC(0-∞)], last time point where the concentration is above the 
limit of quantification (tlast), systemic clearance (CL), volume of distribution at 
steady state (Vss), terminal phase elimination rate constant (λz), terminal phase half-
life (t½)  
For cys-mcMMAF, Cmax, tmax, AUC [AUC(0-t), AUC (0-tau) and/or AUC(0-∞)], tlast, 
λz, and t½ will be computed at Cycle 1 and Cycle 3, as data permit. 
Plasma belantamab mafodotin concentration-time data may be combined with data from 
other studies and will be analyzed using a population pharmacokinetic approach. A 
nonlinear mixed effects model will be used to determine population pharmacokinetic 
parameters (clearances, CL and volumes of distribution, V) and identify important 
covariates (e.g., age, weight, or disease-related covariates). Summary exposure measures 
(e.g., Cmax, AUC) will also be computed. For the data from the lyophilized 
configuration, individual pharmacokinetic parameters may be obtained using a Bayesian 
approach and the population PK model. Results of this analysis may be provided in a 
separate report. 
9.5.4.2. 
Statistical Analysis of Pharmacokinetic Data 
Statistical analyses of the pharmacokinetic (PK) parameters data will be the responsibility 
of Clinical Statistics, GSK. 
belantamab mafodotin (ADC and total mAb) and cys-mcMMAF concentration-time data 
will be listed for each participant and summarized by descriptive statistics at each time 
point (when appropriate) by planned time point and dose level as needed.  
Pharmacokinetic parameters will be listed and summarized descriptively (mean, standard 
deviation, median, minimum, maximum, geometric mean, and the standard deviation, 
CV%, and 95% CI of log-transformed parameters) by cycle, dose level, and 
configuration. 
9.5.5. 
Pharmacokinetic/Pharmacodynamic Analyses 
If deemed appropriate and if data permit, exposure-response relationships between 
belantamab mafodotin exposure (e.g., dose, dose intensity, concentration, Cmax, or 

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AUC) and clinical activity and/or toxicity (e.g., response, corneal event, AESIs) may be 
explored using population methods. If data permit, the effects of covariates may be 
explored. Results of this analysis may be provided in a separate report. 
9.5.6. 
Translational Research Analyses  
The results of translational research investigations will be reported either within or 
separately from the main clinical study report (CSR). All endpoints of interest from all 
comparisons will be descriptively and/or graphically summarized as appropriate to the 
data. 
Further details on the translational research analyses will be addressed in the RAP. 
9.5.6.1. 
Analysis of Novel Biomarker Data 
The results of these biomarker investigations may be reported separately from the main 
clinical study report. All endpoints of interest from all comparisons will be descriptively 
and/or graphically summarized as appropriate to the data. 
Additional exploratory analyses may be performed to further characterize the novel 
biomarker. 
9.5.6.2. 
Analysis of Genetic Data 
Further details on genetic analyses are addressed in Appendix 6. 
9.5.6.3. 
Exploratory Analyses of DNA and Protein Data 
Exploratory analyses may be performed on remaining study samples for analyses of 
DNA, RNA and protein to understand changes in response to the combination treatment 
with belantamab mafodotin. 
The results of exploratory investigations will be reported separate from the main CSR. 
All endpoints of interest from all comparisons will be descriptively and/or graphically 
summarized as appropriate to the data. 
9.5.7. 
Analyses of Immunogenicity Data  
For each participant, the results and titers of anti-belantamab mafodotin binding 
antibodies will be listed for each assessment time point, along with the time-matched 
belantamab mafodotin plasma concentration. The frequency and percentage of 
participants with positive and negative results will be summarized for each assessment 
time and overall for each participant by dose cohort. The detailed information will be 
included in the RAP. 
9.5.8. 
Other Analyses 
Participant disposition, treatment status, demographics, medical history, prior and 
concomitant medications, prior anti-cancer therapies, and study treatment exposure will 
be summarized descriptively and listed by participant. 

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In addition, the impact of COVID-19 will be evaluated at the end of study analysis. 
Details of such analysis will be provided in the updated reporting and analysis plan.  
9.5.9. 
Interim Analyses 
9.5.9.1. 
Futility Stopping Rule Based on Group Sequential Design 
For each arm (2.5 mg/kg or 3.4 mg/kg of frozen liquid solution), one single futility IA is 
planned for ORR based on investigator’s assessment, after approximately 25 participants 
(~38% information fraction of initially planned 65 participants) per arm are evaluable. A 
user-defined gamma spending function (γ=1.1) [Hwang, 1990] was used as a beta-
spending function to determine the non-binding futility boundary (as implemented in East 
6.4). With this β-spending function, the stopping boundary in IA is identified as 0.16 on 
the proportion scale (≤4 responders out of 25 participants), which is close to the historical 
control of 0.15. The spending function and associated boundary were chosen to ensure 
good operating characteristics, specifically, the type 1 error and power are well 
controlled.  
A two-step approach is used to identify the futility stopping rule based on a group 
sequential design under the assumption of exact binomial distribution.  
First, as described in Section 9.2, an initial design based on the assumption of normal 
approximation of binomial proportion is identified by East 6.4. 
The interim futility and final efficacy analysis boundaries were then converted to number 
of responders needed in 25 participants who are evaluable at IA and the 65 participants 
initially planned at the final analysis. 
With a total sample size of 100 participants per arm and an IA with approximately 25 
participants per arm, the same futility boundary (≤ 4 responders out of 25 participants) 
will still apply with a user-defined gamma spending function (γ=5.4). For the final 
analysis, the boundary for claiming efficacy is the minimum number of responders 
required for the lower bound of the two-sided 97.5% C.I. to exceed 15% (i.e. 24 
responders for sample size of 100 per arm).  
Statistical properties of the group sequential design with sample sizes of 65, and 100 per 
arm are summarized in Table 19. 
Table 19 
Probabilities of Crossing Boundaries at the Interim or Final ORR 
Analysis based on Group Sequential Design 
Look 
Sample 
Size (per 
arm) 
Boundaries 
Cumulative Boundary Crossing 
Probabilities 
# of Responders 
Under H0 
Under H1 
Interim (futility) 
25 
≤4 
68.21% 
4.96% 
Final (Efficacy) 
65 
17 
1.23% 
88.00% 
100 
24 
0.97% 
93.70% 
Note: The Cumulative Boundary Crossing Probabilities are calculated based on exact binomial distribution 
theoretically. 

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9.5.9.2. 
Additional Comparative Futility Stopping Rule Based on Bayesian 
Approach 
If both arms pass the futility boundaries based on group sequential design described 
above, posterior probability of observing a better RR in one arm relative to the other will 
be calculated. If such a probability is at least 97.5%, then the treatment arm with lower 
RR will be dropped due to lack of efficacy. This additional guidance was put in to allow 
for dropping an arm with substantially inferior response rates (e.g. absolute difference > 
28%). 
To calculate the posterior probability, a non-informative Beta prior (0.025, 0.1) will be 
used for each arm. Details about calculating the posterior probabilities are provided in 
Appendix 12.  
Statistical properties for different scenarios based on both futility rules are summarized in 
Table 20. 
Table 20 
Probabilities of Stopping for Futility at the Interim or Claiming 
Efficacy at the Final ORR Analysis based on Both Futility Rules 
Scenarios 
Participant
s per arm 
Response Rate 
Futility Stopping 
Boundary Crossing 
Probabilities at IA [1] 
Probabilities of 
Claiming Efficacy at 
Final [1] 
Arm 1 [2] 
Arm 2 
[2] 
Arm 1 [2] 
Arm 2 [2] 
Arm 1 [2] 
Arm 2 [2] 
1 
65 
33% 
60% 
53.59% 
0.01% 
44.83% 
99.99% 
2 
65 
33% 
45% 
16.95% 
0.47% 
77.94% 
99.49% 
3 [3] 
65 
33% 
33% 
6.33% 
6.33% 
86.90% 
86.92% 
4 
65 
33% 
25% 
5.09% 
23.83% 
87.89% 
42.39% 
5 
65 
33% 
20% 
4.97% 
44.59% 
87.98% 
12.52% 
6 
65 
33% 
15% 
4.96% 
69.99% 
87.99% 
1.20% 
7 
65 
33% 
10% 
4.96% 
90.85% 
87.99% 
0.01% 
8 [4] 
65 
15% 
15% 
68.22% 
68.22% 
1.23% 
1.24% 
9 
100 
33% 
60% 
53.59% 
0.01% 
46.11% 
99.99% 
10 
100 
33% 
45% 
16.95% 
0.47% 
82.09% 
99.53% 
11 [3] 
100 
33% 
33% 
6.33% 
6.33% 
92.38% 
92.39% 
12 
100 
33% 
25% 
5.09% 
23.83% 
93.57% 
53.93% 
13 
100 
33% 
20% 
4.97% 
44.59% 
93.68% 
15.46% 
14 
100 
33% 
15% 
4.96% 
69.99% 
93.70% 
0.94% 
15 
100 
33% 
10% 
4.96% 
90.85% 
93.70% 
0.003% 
16 [4] 
100 
15% 
15% 
68.22% 
68.22% 
0.97% 
0.97% 
Note:  
[1] The Boundary Crossing Probabilities are calculated based on 10,000,000 simulations using R program.  
[2] Arm 1 and Arm 2 in the table just represent two different treatment arms and are not necessarily refers to 3.4 
mg/kg and 2.5 mg/kg, respectively.  
[3] The power is shown in Scenario 3, and 11 as 86.90% and 92.38% for sample size of 65, and 100 respectively. 

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[4] The type I error is shown in Scenario 8, and 16 as 1.23%, and 0.97% for sample size of 65, and 100 respectively. 
The IA to assess futility will be reviewed by an Independent Data Monitoring Committee 
(IDMC). Additional details of the IA are provided in Section 9.5.9 and will be provided 
in an IDMC Charter. The stopping rules described above are guidelines for decision-
making and the totality of the data will be considered when making a final decision. 
Participants will continue to be enrolled, dosed, and followed as planned at the time of 
IA. 

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10. 
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rate, durability of response, and survival after thalidomide therapy for relapsed multiple 
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Improved survival in multiple myeloma and the impact of novel therapies. Blood. 
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Macsai M, Nariani A, Gan H, Lassman A, Merrell R, Gomez E, et al. Corneal Toxicity of 
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11. 
APPENDICES 
11.1. 
Appendix 1: Abbreviations and Trademarks 
ADA 
Anti-drug antibodies 
ADC 
Antibody drug conjugate 
ADCC 
Antibody dependent cellular cytotoxicity 
ADL 
Activities of daily living 
AE 
Adverse Event 
AESI 
Adverse events of special interest 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
Anti-CD38 
Anti-CD38 antibody 
APRIL 
A proliferation-inducing ligand 
AST 
Aspartate aminotransferase 
AUC 
Area under the curve 
AV 
Atrioventricular 
BAFF 
B-cell-activating factor belonging to the TNF family 
BCMA 
B-cell maturation antigen 
BCVA 
Best corrected visual acuity 
BIB 
Bioanalysis Immunogenicity and Biomarkers 
BiTe 
Bispecific antibodies 
BLRM  
Bayesian Logistic Regression Model 
BM 
Bone marrow 
BNP 
B-type natriuretic peptide 
BP 
Blood Pressure 
BUN 
Blood urea nitrogen 
C1D1 
Cycle 1 Day 1 
CAR-T 
Chimeric antigen receptor T-Cell 
CBR 
Clinical Benefit Rate 
cfDNA 
Circulating cell-free deoxyribonucleic acid 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CIOMS 
Council of International Organizations of Medical Sciences 
CK 
Creatine kinase 
CL 
Clearance 
Cmax 
Maximum observed concentration 
CO2 
Carbon dioxide 
CONSORT 
Consolidated Standards of Reporting Trials 
COPD 
Chronic Obstructive Pulmonary Disease 
CPK 
Creatine phosphokinase 
CR 
Complete Response 
CRF 
Case Report Form 
CRP 
C-reactive protein 
CSR 
Clinical study report 

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CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Coefficient of variation 
DAMPs 
Danger-associated molecular patterns 
DCs 
Dendritic cells 
DICOM 
Digital Imaging and Communications in Medicine 
DILI 
Drug-induced liver injury 
DLT 
Dose limiting toxicities 
DNA 
Deoxyribonucleic acid 
DOR 
Duration of Response 
EC 
Ethics committee 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
eGFR 
Estimated glomerular filtration rate 
EOI 
End of infusion 
EOS 
End of study 
EORTC 
European Organization for Research and Treatment of Cancer 
EOT 
End of treatment 
EQ-5D-5L 
EuroQOL Group EQ-5D 5 Level 
FISH 
Fluorescence in situ hybridization 
FLC 
Free light chain 
FSFV 
First subject first visit 
FSH 
Follicle stimulating hormone 
FTIH 
First Time in Human Trial 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GGT 
Gamma glutamyl transferase 
GSK 
GlaxoSmithKline 
HBV 
Hepatitis B 
HCV 
Hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
HLA 
Human leukocyte antigen 
HR 
Hazard ratio 
HRT 
Hormone replacement therapy 
HSCT 
Hematopoietic stem cell transplantation 
IB 
Investigator Brochure 
ICD 
Immunogenic cell death 
ICH 
International Conference on Harmonization 
IDMC 
Independent Data Monitoring Committee 
IEC 
Institutional Ethics Committee 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 

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IHC 
Immunohistochemistry 
IMWG 
International Myeloma Working Group 
INR 
International normalization ratio 
IP 
Investigational product 
IRB 
Institutional review board 
IRC 
Independent Review Committee 
IRR 
Infusion related reaction 
IRT 
Interactive Response Technology 
IUD 
Intra-uterine device 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous 
KVA 
Keratopathy Visual Acuity Scale 
LC 
Light chain  
LDH 
Lactate dehydrogenase 
LLN 
Lower limit of normal (range) 
LSFD 
Last subject first dose 
LSFV 
Last subject’s first visit 
LSLV 
Last subject last visit 
LVEF 
Left ventricular ejection fraction 
mAb 
Monoclonal antibody 
MDRD 
Modified diet in renal disease 
MM 
Multiple myeloma 
MMAF 
Monomethyl auristatin-F 
MOA 
Mechanism of Action 
mOS 
Median overall survival  
mPFS 
Median progression free survival  
MR 
Minimal Response 
MRD 
Minimal residual disease 
MRI 
Magnetic resonance imaging 
MSDS 
Material Safety Data Sheet 
NCI 
National Cancer Institute 
NE 
Not evaluable 
NEI-VFQ-25 
National Eye Institute 25-Item Visual Function Questionnaire 
NGS 
Next Generation Sequencing  
NR 
Not reported  
NYHA 
New York Heart Association 
OATP 
Organic Anion Transporting Proteins 
ORR 
Overall Response Rate 
OS 
Overall survival 
OSDI 
Ocular Surface Disease Index 
PACT 
Post Analysis Continued Treatment 
PCR 
Polymerase chain reaction 
PD 
Progressive disease 
PET 
Positron Emission Tomography 
PFS 
Progression Free Survival 
PI 
Principal Investigator 

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PK 
Pharmacokinetics 
PR 
Partial response 
PRO 
Patient reported outcome 
PRO-CTCAE Patient-Reported Outcome Version of the Common Term Criteria for 
Adverse Events 
PTS 
Platform Technologies and Science 
Q21D 
Once every 21 days 
Q3W 
Once every 3 weeks 
QID 
Four times a day 
QLQ-C30 
Quality of Life Questionnaire 30-item Core module 
QLQ-MY20 
Quality of Life Questionnaire 20-item Multiple Myeloma module 
QTc 
Corrected QT interval (ECG) 
QTcF 
Corrected QT interval Fridericia 
RAMOS 
Registration and Medication Ordering System 
RAP 
Reporting and Analysis Plan 
RBC 
Red blood cell 
RNA 
Ribonucleic acid 
RP2D 
Recommended Phase II Dose 
RRMM 
Relapsed / refractory multiple myeloma 
SAE 
Serious adverse event 
sBCMA 
Soluble B-cell maturation antigen 
sCR 
Stringent Complete Response 
SCT 
Stem cell transplant 
SD 
Stable disease 
SOA 
Schedule of activities 
SOI 
Start of infusion 
SOP 
Standard operating procedure 
SPD 
Sum of the products of the maximal perpendicular diameters of 
measured lesions 
SPEP 
Serum Protein Electrophoresis 
SRM 
Study Reference Manual 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
SUV 
Standardized uptake value 
t½ 
Terminal phase half-life 
TCR 
T-Cell receptor 
TLS  
Tumor Lysis syndrome  
tmax 
Time of maximum observed concentration 
TNF 
Tumor necrosis factor 
TTP 
Time to progression 
TTR 
Time to (best) Response 
TTR 
Time to response 
UK 
United Kingdom 
ULN 
Upper limit of normal 
UPEP 
Urine protein electrophoresis 
US 
United States 
USP 
United States Pharmacopeia 

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V 
Volume of distribution 
VA  
Visual Acuity 
VGPR 
Very good partial response 
WBC 
White blood cell 
WFI 
Sterile water for injection 
WOCBP 
Woman of Childbearing Potential  
β-HCG 
Beta human chorionic gonadotropin 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
NONE 
 
NONE 
 
 
 
 
 
 
 
 

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11.2. 
Appendix 2: Clinical Laboratory Tests 
• 
The tests detailed in Table 14 are identified as being performed at either local or 
central laboratory.  
• 
For response assessments, local laboratory results are only required in the event 
that the central laboratory results are not available in time for response 
evaluation. If a local sample is required, it is important that the sample for 
central analysis is obtained at the same time.  
• 
Protocol-specific requirements for inclusion or exclusion of participants are 
detailed in Section 5 of the protocol. 
• 
Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations. 
• 
Pregnancy testing (see Section 5.1 [Inclusion Criteria] for screening pregnancy 
criteria) 
• 
Pregnancy testing (urine or serum as required by local regulations) should be 
conducted at monthly intervals during intervention  
• 
Pregnancy testing (urine or serum as required by local regulations) should be 
conducted at the end of relevant systemic exposure plus an additional 30 days 
and correspond with the time frame for female participant contraception in 
Section 5.1 (Inclusion Criteria). 
 

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11.3. 
Appendix 3: Study Governance Considerations 
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 IEC/IRB approval before 
implementation of changes made to the study design, 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/EC 
• 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 
regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations 
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. 
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.  

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• 
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.  
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.  
• 
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. 
Committees Structure 
An IRC will be utilized to assess response and progression and primary endpoint of 
the study. Digital copies of all scans must be maintained at Investigator site as source 
document. Further details on the IRC process will be defined in the IRC charter 
Results from the IRC will not be provided to the investigative sites during the study.  
 
Participant data to be shared with the IRC may include the following: 
• Scans (CT, MRI, or PET CT- whichever applicable) 
• SPEP, UPEP, M-protein in 24 hr. urine collection immunoelectrophoresis- 
urine and serum, serum calcium, and albumin (unless reported as albumin 
corrected),  
• Serum kappa, serum lambda FLC, FLC Ratio 
• MRD results 

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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. 
Dissemination of Clinical Study Data 
For studies conducted in the EU under Regulations EU 536/2014: Consider whether 
submission of results of the clinical study will be delayed more than one year after the 
end of trial and provide substantiated reasons. Provide justification if a single summary of 
results report will not be submitted for all study treatments used in the clinical study. 
• 
Disclosure of 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. 
• 
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. 

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• 
A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 
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 CRF.  
• 
The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF.  
• 
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 CRF 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.  
• 
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 or as locally agreed 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.  
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. 

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Study and Site Closure 
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: 
• 
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 recruitment of participants by the investigator 
• 
Discontinuation of further study treatment development 
 

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11.4. 
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
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 it 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 fulfill 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. 

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• 
The disease/disorder being studied or expected progression, signs, or symptoms of 
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. 
 
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: 
Results in death 
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. 
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 fulfills 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. 
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, 

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influenza, and accidental trauma (e.g., sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
Is a congenital anomaly/birth defect 
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. 
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. 
Refer to Appendix 7 for liver chemistry follow-up procedures. 
 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs: 
• 
Myocardial infarction/unstable angina 
• 
Congestive heart failure 
• 
Arrhythmias 
• 
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• 
Pulmonary hypertension 
• 
Cerebrovascular events/stroke and transient ischemic attack 
• 
Peripheral arterial thromboembolism 
• 
Deep venous thrombosis/pulmonary embolism 
• Revascularization 
 
Recording 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 CRF. 
• 
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 CRF 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 make an assessment of 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.  
Grade 2: Moderate; minimal, local or noninvasive 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. 
 

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*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 Investigator’s Brochure (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. 
 
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 CRF. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 

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Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• 
The primary mechanism for reporting SAE 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. 
• 
The investigator or medically-qualified sub-investigator must show evidence 
within the eCRF (e.g., check review box, signature, etc.) of review and verification 
of the relationship of each SAE to IP/study participation (causality) within 72 
hours of SAE entry into the eCRF. 
• 
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 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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11.5. 
Appendix 5: Contraceptive Guidance and Collection of 
Pregnancy Information 
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 females with ONE 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 females 
• 
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 one FSH measurement is required.  
• 
Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen 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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Contraception Guidance 
• 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
• 
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. 
c. 
Male condoms must be used in addition to hormonal contraception. If locally required, in accordance with 
Clinical Trial Facilitation Group (CTFG) 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 (LAM) 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) 
 
 
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 of a male study participant who becomes pregnant while participating 

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in this study and for 6 months following last dose of study treatment. This applies 
only to male participants who receive study intervention. 
• 
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 last 
dose of study treatment.  
• 
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.  
• 
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study intervention by the investigator, will be reported to 
GSK as described in Appendix 4. 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 
intervention.  
 

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11.6. 
Appendix 6: Genetics 
USE/ANALYSIS OF DNA 
• 
Genetic variation may impact a participant’s response to therapy, susceptibility, 
severity and progression of disease. Variable response to therapy 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 6-mL blood sample will be collected from participants who have consented 
to participate 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 treatments of this 
drug class, and Multiple Myeloma. Genetic research may consist of the analysis of 
one 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 described planned analyses. Additional analyses 
will be conducted if it is hypothesized that this may help further understand the 
clinical data.  
• 
The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to belantamab mafodotin or study treatments 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 
treatments of this class) or Multiple Myeloma continues but no longer than 15 years 
after the last subject last visit or other period as per local requirements. 
 

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11.7. 
Appendix 7: Liver Safety: Required Actions and Follow-up 
Assessments and Study Treatment Rechallenge Guidelines 
Phase I/II 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 5xULN 
ALT Increase 
ALT 3xULN persists for 4 weeks 
Bilirubin1, 2 
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin)  
INR2  
ALT 3xULN and INR >1.5, if INR measured 
Cannot Monitor 
ALT 3xULN 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 and Follow up Assessments following ANY Liver Stopping Event 
Actions 
Follow Up Assessments 
• 
Report the event to GSK within 24 hours 
• 
Complete the liver event CRF and complete 
an SAE data collection tool if the event also 
meets the criteria for an SAE2 
• 
Perform liver event follow up assessments  
• 
Monitor the participant until liver chemistries 
resolve, stabilize, or return to within 
baseline (see MONITORING below) 
• 
Do not restart/rechallenge participant with 
study treatment unless allowed per protocol 
and GSK Medical Governance approval is 
granted (refer to language within this 
Appendix)  
• 
If restart/rechallenge not allowed per 
protocol or not granted, permanently 
discontinue study treatment and may 
continue participant in the study for any 
protocol specified follow up assessments  
MONITORING: 
For bilirubin or INR criteria:  
• 
Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
• 
Viral hepatitis serology4 
• 
Only in those with underlying chronic hepatitis B 
at study entry (identified by positive hepatitis B 
surface antigen) quantitative hepatitis B DNA and 
hepatitis delta antibody5.  
• 
Blood sample for pharmacokinetic (PK) analysis, 
if it can be obtained within 45 days after last dose  
• 
Serum creatine phosphokinase (CPK) and 
lactate dehydrogenase (LDH). 
• 
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 AE report form 
• 
Record use of concomitant medications on the 
concomitant medications report form including 
acetaminophen, herbal remedies, other over the 
counter medications 
• 
Record alcohol use on the liver event alcohol 
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liver event follow up assessments within 24 
hrs 
• 
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:  
• 
Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within 24-
72 hrs  
• 
Monitor participants weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
For bilirubin or INR criteria: 
• 
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 HPLC assay 
(quantifies potential acetaminophen contribution 
to liver injury in participants with definite or likely 
acetaminophen use in the preceding week 
[James, 2009]) Note: not required in China  
• 
Liver imaging (ultrasound, magnetic resonance, 
or computerized tomography) and /or liver biopsy 
to evaluate liver disease; complete Liver Imaging 
and/or Liver Biopsy CRF forms. 
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that participant if ALT 3xULN and 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 bilirubin  2xULN (>35% direct bilirubin) or ALT 3xULN and INR>1.5, if INR 
measured which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE 
(excluding studies of hepatic impairment or cirrhosis); INR measurement is not required and the 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  
5. If hepatitis delta antibody assay cannot be performed, it can be replaced with a PCR of hepatitis D RNA virus 
(where needed) [Le Gal, 2005]. 
6. Record the date/time of the PK blood sample draw and the date/time of the last dose of study treatment 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 sample cannot be collected 
in the time period indicated above, do not obtain a PK sample.  
 

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Phase I/II Oncology liver chemistry increased monitoring criteria with continued 
therapy 
Liver Chemistry Increased Monitoring Criteria – Liver Monitoring Event 
Criteria 
Actions 
ALT 3xULN but <5xULN and 
 bilirubin <2xULN, 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 treatment  
• 
Participant must return weekly for repeat liver 
chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) until they resolve, stabilize or return to 
within baseline  
• 
If at any time participant meets the liver chemistry 
stopping criteria, proceed as described above 
• 
If, after 4 weeks of monitoring, ALT <3xULN and 
bilirubin <2xULN, monitor participants twice 
monthly until liver chemistries normalize or return 
to within baseline. 
11.7.1. 
Liver Safety Drug Restart or Re-Challenge Guidelines 
If participant meets liver chemistry stopping criteria do not restart/re-challenge 
participant with study treatment unless all the following conditions are met: 
• 
GSK Medical Governance approval is granted (as described below) 
• 
IRB/IEC approval is obtained, if required 
• 
Separate consent for treatment restart/re-challenge is signed by the participant 
If GSK Medical Governance approval to restart/re-challenge participant with study 
treatment is not granted, then participant must permanently discontinue study treatment 
and may continue in the study for protocol-specified follow up assessments. 
11.7.1.1. 
Re-challenge Following Liver Stopping Events that are Possibly 
Related to Study Treatment 
Re-challenge refers to resuming study treatment following drug-induced liver injury 
(DILI). Because of the risks associated with re-challenge 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 re-challenge is considered to be favorable. 
Following DILI, drug re-challenge is associated with a 13% mortality across all drugs in 
prospective studies [Andrade, 2009]. Clinical outcomes vary by drug with nearly 50% 

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fatality with halothane re-administered within 1 month of initial injury. However, some 
drugs seldom result in recurrent liver injury or fatality.  
Risk factors for a fatal drug re-challenge outcome include the following: 
• 
Hypersensitivity1 with initial liver injury (e.g., fever, rash, eosinophilia)  
• 
Jaundice or bilirubin >2 x ULN with initial liver injury (direct bilirubin >35% of 
total) 
• 
Participant currently exhibits severe liver injury defined by ALT >3 x ULN, bilirubin 
>2 x ULN (direct bilirubin >35% of total), or INR >1.5 
• 
SAE or fatality has been observed with drug rechallenge [Papay, 2009; Hunt, 2010] 
• 
Evidence of drug-related preclinical liability (e.g., reactive metabolites; 
mitochondrial impairment) [Hunt, 2010] 
Approval by GSK for re-challenge with study treatment can be considered under the 
following conditions: 
• 
Investigator requests consideration of re-challenge 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 re-challenge with study treatment must be obtained, as 
required.  
• 
If the re-challenge is approved by GSK Medical Governance 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 
re-challenge with study treatment. Documentation of informed consent must be 
recorded in the study chart.  
• 
Study treatment must be administered at the dose specified by GSK. 
• 
Participants approved by GSK Medical Governance for re-challenge 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 re-challenge, participant meets protocol-defined liver 
chemistry stopping criteria, study treatment must be permanently discontinued.  
• 
GSK medical monitor, and the IRB/IEC as required, must be informed of the 
participant’s outcome following study treatment re-challenge.  
• 
GSK must be notified of any AEs as per Section 8.2.4. 

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11.7.1.2. 
Re-challenge Following Transient 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, and acute viral hepatitis). Furthermore, there should be 
no evidence of alcoholic hepatitis or hypersensitivity, and the study treatment should not 
be associated with human leukocyte antigen (HLA) markers of liver injury. 
Approval by GSK for study treatment restart can be considered under the following 
conditions: 
• 
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-related liver injury has been excluded by the 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 re-challenge in 
Section 11.7.1.1 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 treatment is approved by GSK Medical Governance 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 
chart. 
• 
Study treatment must be administered at the dose specified by GSK. 
• 
Participants approved by GSK Medical Governance for restarting 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 after study treatment restart, participant meets protocol-defined liver chemistry 
stopping criteria, follow usual stopping criteria instructions. 
• 
GSK medical monitor, and the IRB/IEC as required, must be informed of the 
participant’s outcome following study treatment restart. 
• 
GSK must be notified of any AEs, as per Section 8.2.4. 

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11.7.2. 
References 
Andrade RJ, Robles M, Lucena MI. Rechallenge in drug-induced liver injury: the 
attractive hazard. Expert Opin Drug Saf. 2009;8:709-714. 
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. 
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. 
Papay JI, Clines D, Rafi R, Yuen N, Britt SD, Walsh JS, Hunt CM. Drug-induced liver 
injury following positive drug rechallenge. Regul Tox Pharm. 2009;54:84-90.  
 
 

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11.8. 
Appendix 8: ECOG Performance Status 
Grade Descriptions 
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, office work). 
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. 
Oken,1982 

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11.9. 
Appendix 9: GSK/KVA Scale and Mitigation Strategy for 
Belantamab Mafodotin Treatment-Related Corneal Events 
In order to minimize corneal events associated with belantamab mafodotin prophylactic 
preservative-free artificial tears should be administered in each eye at least 4 to 8 times 
daily beginning on Cycle 1 Day 1 until the EOT. In the event of ocular symptoms (e.g., 
dry eyes), the use of artificial tears may be increased up to every 2 hours as needed. 
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 subsequently decrease ocular side effects. On the day of infusion at the 
discretion of the participant and the investigator, the following may be considered:  
• 
Beginning with the start of each belantamab mafodotin infusion, participants may 
apply cooling eye masks to their eyes for approximately 1 hour or as much as 
tolerated.  
• 
Participants may continue using the cooling eye mask beyond the first hour for up to 
4 hours. Further use beyond 4 hours is at the participant’s discretion. 
Participants must avoid the use of contact lenses during the study. 
An ophthalmology (or optometry, if ophthalmology is not available) consult is required 
for all participants who develop signs or symptoms of corneal events or require steroid 
eye drops for more than 7 days. 
Following discussions with regulatory agencies, GSK developed a grading scale for 
corneal events to capture both corneal findings and visual acuity changes in participants 
treated with belantamab mafodotin. This GSK/KVA scale is different from CTCAE 
criteria for eye disorders which relies mainly on patient’s symptoms and patient’s ability 
to attend to ‘activities of daily living’ for grading of events.  
A summary of prophylactic interventions for corneal events associated with belantamab 
mafodotin is provided in Table 21. In addition to reporting eye disorders using CTCAE 
4.03 criteria, corneal events associated with belantamab mafodotin must be graded 
according to the guidelines provided in Table 22. Additional guidance on visual acuity 
changes is provided in Table 23. 
In the FTIH study (BMA117159), eye examinations showed that most participants 
continued to receive belantamab mafodotin dose when either a GSK/KVA Scale Grade 2 
corneal examination finding or a 2-3-line decrease in visual acuity was reported. With 
this dosing paradigm, participants generally showed improvement in both corneal 
examination findings and visual acuity over time. Therefore, the dosing guideline has 
been adjusted to allow dosing with belantamab mafodotin if only one component on the 
GSK/KVA scale indicates Grade 2 corneal event. 

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Table 21 
Prophylactic Measures for Corneal Events Associated with 
Belantamab Mafodotin a 
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.  
Cooling eye mask 
May apply cooling eye mask to 
both eyes for approximately 
1 hour or as much as tolerated  
During belantamab mafodotin infusion 
administration in the first hour for up to 
4 hours, as tolerated 
a. 
Dose modifications and treatment for ocular toxicities are discussed in Section 6.2 
 
Table 22 
GSK/KVA Scale for Corneal Events Associated with Belantamab 
Mafodotin a 
Measure 
Grade 1 per 
GSK/KVA 
Scale  
Grade 2 per 
GSK/KVA Scale 
Grade 3 per 
GSK/KVA Scale 
Grade 4 per 
GSK/KVA 
Scale 
Ophthalmic 
exam 
findings 
Mild superficial 
keratopathy 
(change from 
baseline) 
 
Moderate punctate 
keratopathy 
and/or 
Mild/patchy 
microcysts 
and/or 
Mild/patchy Epithelial 
or stromal edema 
and/or 
Sub-epithelial haze 
(peripheral)  
and/or 
Active stromal opacity 
(peripheral) 
Severe punctate 
keratopathy 
and/or 
Diffuse microcysts 
and/or 
Diffuse Epithelial or 
stromal edema 
and/or 
Sub-epithelial haze 
(central)  
and/or 
Active stromal opacity 
(central) 
Corneal ulcer 
Visual 
Acuity b, c 
Change of 1 line 
from baseline 
Change of 2-3 lines 
from baseline and not 
worse than 20/200b 
Change of more than 3 
lines from baseline and 
not worse than 20/200b 
Worse than 
Vision 20/200b 
Note: Standardized guidance for grading ophthalmic findings associated with belantamab mafodotin is provided to sites 
in the ophthalmology SRM. Ophthalmic exam findings as described must be present in a participant to utilize 
GSK’s scale.  
a. 
Grading is based on most severe finding. If eyes differ in severity, GSK grading should be based on the more 
severe eye. 
b. 
Change in visual acuity should be due to corneal events. If change in vision is for reason other than corneal 
events, ophthalmic exam findings will drive event grading.  
c. 
See Table 23 for additional guidance on how to grade changes in visual acuity depending on baseline vision. If a 
participant has a baseline visual acuity of 20/200 or worse in an eye, ophthalmic exam findings will drive event 
grading. 
 
 
 

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Table 23 
Guidance on GSK/KVA Scale Grading Based on Changes in Visual 
Acuity 
Baseline Vision 
(best corrected) 
Grade 1 per 
GSK scale  
Grade 2 per GSK 
scale 
Grade 3 per GSK 
scale 
Grade 4 per GSK 
scale 
20/15 - 20/20 
20/25 
20/30 – 20/40  
20/50 –20/200 
Worse than 20/200  
20/25 
20/30 
20/40 – 20/50 
20/60 –20/200 
Worse than 20/200 
20/30 
20/40 
20/50 – 20/60 
20/70 –20/200 
Worse than 20/200 
20/40 
20/50 
20/60 – 20/70 
20/80 –20/200 
Worse than 20/200 
20/50 
20/60 
20/70 – 20/80 
20/100 – 20/200 
Worse than 20/200 
20/60 
20/70 
20/80 – 20/100 
20/125 – 20/200 
Worse than 20/200 
20/70 
20/80 
20/100 – 20/125 
20/200  
Worse than 20/200 
20/80 
20/100 
20/125 – 20/200 
N/A 
Worse than 20/200 
20/100 
20/200 
20/200  
N/A 
Worse than 20/200  
 
 

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11.10. 
Appendix 10: Modified Diet in Renal Disease (MDRD) 
Formula 
The MDRD formula for calculating the estimated glomerular filtration rate (eGFR) is as 
follows: 
eGFR (mL/min/1.73 m2) = 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 link below will auto-calculate the creatinine clearance: http://nephron.org/cgi-
bin/MDRD_GFR/cgi 

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11.11. 
Appendix 11: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
Amendment 06: 19-Nov-2021 
Overall Rationale for the Amendment:  
The protocol has been amended to provide updates including the addition of the end of 
study definition section (Section 4.6) and continued access to study intervention after the 
end of the study (Post Analysis Continued Treatment [PACT]) (Section 6.9). 
Section # and Name Description of Change 
Brief Rationale  
Section 1.1 Synopsis 
Additional content to the overall study 
has been added which includes PACT 
implementation and End of Study 
definition 
To introduce the approved 
standard language for 
belantamab mafodotin studies 
implementing PACT  
Section 2.4.4 
Pharmacokinetics 
and 
Pharmacodynamics 
Revision of pharmacokinetics and 
pharmacodynamics section as per 
latest information available in IB 
Section updated as per latest 
information available in IB 
Section 4.1 Overall 
Design 
Additional content added to align to 
PACT implementation 
To introduce the approved 
standard language for 
belantamab mafodotin studies 
implementing PACT 
Section 4.6 End of 
Study Definition 
New section added to align to PACT 
implementation and additional content 
added related to PACT 
To introduce the approved 
standard language for 
belantamab mafodotin studies 
implementing PACT  
Section 6.9 
Continued Access to 
Study Intervention 
after the End of the 
Study 
New section added to align to PACT 
implementation and additional content 
added related to PACT  
To introduce the approved 
standard language for 
belantamab mafodotin studies 
implementing PACT  
Section 8.2.1 Time 
Period and 
Frequency for 
Collecting AE and 
SAE Information  
Additional content added to align to 
PACT implementation 
To introduce the approved 
standard language for 
belantamab mafodotin studies 
implementing PACT  
 

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Amendment 5: 08-Oct-2020 
Overall Rationale for the Amendment:  
The protocol has been amended to provide updates based on analyses of data from the 
DREAMM-1, DREAMM-2 and the exposure QTc. The updates include the removal of 
ECG collection, unless clinically indicated, and updated contraception timeframe. The 
dose modification guidelines for belantamab mafodotin related corneal events was 
updated to align with the approved label and an appendix on Home Healthcare and 
Telemedicine Approaches was introduced as a result of the COVID-19 pandemic to 
ensure sites and participants had alternate approaches to assist participants to continue 
receiving care while maintaining protocol adherence. 
Section # and Name Description of Change 
Brief Rationale  
Section 2 Schedule 
of Activities  
Study Assessment ECG and 
associated footnotes with mention of 
ECGs (footnote 10, 12, 13) amended to 
remove ECG unless clinically indicated. 
 
 
Table 2, footnote 27 – deletion of text 
related to discontinuation  
 
 
Table 3, footnote 6 – clarified  
 
 
Table 3, footnote 8, updated pregnancy 
timeframe  
Table 3, ECG assessment and footnote 
9 removed  
 
 
 
Triplicate ECGs were removed 
because the exposure-QTc 
analysis demonstrated that the 
likelihood of a QTc prolongation 
>10 msec is very low following 
administration of belantamab 
mafodotin. 
 
Duplication of text found in 
Table 3, schedule of activities 
for end of treatment and follow 
up 
 
Clarified for consistency with 
Section 7.2.3 Corneal 
Supportive Care Guidelines 
 
To align with current investigator 
brochure 
ECGs are to be performed as 
clinically indicated  
 
 
Updated to align with ocular 
examination timeframe. 

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Section # and Name Description of Change 
Brief Rationale  
Table 3, footnote 17, clarification of 
timeframe collection of NEI-VFQ-25 
and OSDI. 
Section 3.4 Human 
Experience with 
belantamab 
mafodotin 
Section 3.4.1 
Thrombocytopenia 
Section 3.4.2 
Corneal Events 
Section 3.4.3 
Infusion Related 
Reactions 
Section 3.4.4 
Pharmacokinetics 
and 
Pharmacodynamics 
 
Update to Human Experience Sections 
 
To align with the most recent 
data from the analysis of the 
DREAMM-1 (117159) and 
DREAMM-2 (current study, 
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Section 3.5 
Benefit/Risk 
Assessment 
Table 5 Risk Assessment and 
Mitigation Strategy: Corneal events 
updated to include additional corneal 
risks 
Nephrotoxicity – correction of 
abbreviated term 
To align with current Investigator 
brochure 
 
Administrative 
Section 3.5.2 Benefit 
Assessment and 
Section 3.5.3 Overall 
Benefit/Risk 
Conclusions  
 
 
  
Updated entire benefit assessment 
section  
To align with the most recent 
data from the analysis of the 
DREAMM-1 (117159) and 
DREAMM-2 (current study, 
205678) and current investigator 
brochure 
Section 5.3 
Participant and Study 
Completion 
Clarification of end of study definition  
Aligned with Section 7.2.3, 
Corneal Supportive Care 
Guidelines of follow up 
timeframe of corneal events. 
Section 7.2 Dose 
Modifications 
Table 13 Dose modification guidelines 
for belantamab mafodotin treatment 
Updated to match the current 
approved label 

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Section # and Name Description of Change 
Brief Rationale  
related corneal events amended to 
remove symptoms 
Section 8.2.3 QTc 
Interval Stopping 
Criteria 
Section removed 
Based on the exposure-QTc 
analysis results, the likelihood of 
a meaningful QTc 
prolongation (>10 msec) is very 
low following administration of 
belantamab mafodotin. 
Section 9 Study 
Assessments and 
procedures 
Removal of ECGs as a study 
assessment  
Based on the exposure-QTc 
analysis results, the likelihood of 
a meaningful QTc 
prolongation (>10 msec) is very 
low following administration of 
belantamab mafodotin. 
Section 9.3 
Treatment of 
Overdose 
Updated timeframe for resolution of 
AEs/SAEs and concentrations of 
belantamab mafodotin.  
Removed restriction of 
timeframe of 3 months as the 
timeframe can vary. 
 
Section 9.4.4 
Electrocardiogram 
Section removed 
Triplicate ECGs were removed 
because the exposure-QTc 
analysis demonstrated that the 
likelihood of a QTc prolongation 
>10 msec is very low following 
administration of belantamab 
mafodotin. 
 
Section 9.4.6 Patient 
Reported Outcome 
Version of the 
Common Term 
Criteria for Adverse 
Events (PRO-
CTCAE) 
Updated to allow options for 
participants to complete by phone or 
verbal interview 
 
Updated to provide options for 
PRO CTCAE completion  
 
Section 10.5.8 Other 
Analyses 
Addition of COVID-19 analysis 
Due to the pandemic an analysis 
will be completed and outlined in 
the reporting and analysis plan. 
12.5 Appendix 5: 
Contraception 
Guidance and 
Collection of 
Updated timeframe for contraception 
usage in males and females.  
To align with current investigator 
brochure 

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Section # and Name Description of Change 
Brief Rationale  
Pregnancy 
Information and 
Section 9.2.8 
Pregnancy 
Section 12.13 
Appendix 13 Home 
Healthcare and 
Telemedicine 
Approaches 
Addition of Appendix  
As a result of COVID-19 
pandemic, alternate approaches 
were introduced to allow 
participants to adhere to the 
protocol. 
Editorial/Document Formatting Changes  
Whole Document 
GSK2857916 or GSK’916 replaced with 
belantamab mafodotin 
Use generic name  
Whole Document  
GSK Scale replace with GSK/KVA 
Scale 
To align with belantamab 
mafodotin label which notes the 
KVA scale  
 
Amendment 4: 21-Oct-2019 
Overall Rationale for the Amendment:  
The protocol has been amended to provide updates based on data from the primary 
analysis and address feedback from regulatory agencies.  
 
Section # and Name Description of Change 
Brief Rationale  
Section 2 Schedule 
of Activities  
Table 2, Footnote 7 added reference to 
increase monitoring for hematologic 
events 
 
 
Table 2, Footnote 10 clarification of 
timeframe to perform triplicate 
electrocardiograms (ECGs) 
 
Table 2, Footnote 21: clarification  
Based on percentage of Grade 
(Gr) 3-4 hematologic events it 
was determined that more 
frequent monitoring should be 
recommended  
 
To align with Section 9.4.4 
 
Clarification of bone marrow 
(BM) collection for Minimal 
Residual disease (MRD) testing 
timeframe. 

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Section # and Name Description of Change 
Brief Rationale  
 
 
Table 2, treatment for steroid eye drops 
deleted, footnote 26a updated 
 
 
Table 3, Footnote 6 correction of 
timeframe for follow up of corneal 
toxicity 
 
Table 3, Footnote 8 increased 
timeframe for contraception usage in 
males and females.  
 
 
 
 
 
 
Table 3, Footnote 10 Updated 
language on requirements for disease 
assessments required to be completed 
when confirming disease progression. 
 
 
Table 3, Footnote 15; Clarification  
 
 
 
Removed prophylactic use of 
steroid eye drops based on 
based on data from the primary 
analysis 
 
Aligned with Section 7.2.3 
 
 
In May 2019, FDA released 
updated reproductive toxicity 
recommendations for oncology 
pharmaceuticals, including 
guidance on labelling the 
duration of contraception 
following cessation of therapy, to 
minimize any potential risk to a 
developing embryo or fetus 
Inclusion criteria 8&9 not 
updated to align as enrollment 
has closed 
 
 
Clarification of confirmatory 
disease progression 
assessments 
 
 
Clarification of BM collection for 
MRD testing timeframe 

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Section # and Name Description of Change 
Brief Rationale  
Table 3 reference to Footnote 18 for 
OSDI and NEI-VFQ-2; Clarification 
 
 
Table 4, footnote 2; ophthalmologist 
discretion to utilize steroid eye drops  
Clarification of OSDI and NEI-
VFQ-25 follow-up questionnaire 
timepoints 
 
Clarification that ophthalmologist 
has discretion to continue 
utilizing steroid eye drops or 
may discontinue  
Section 3.5.1 Risk 
Assessment 
Table 5 Risk Assessment and 
Mitigation Strategy 
Removed preventative use of steroid 
eye drops 
Updated potential risk of Hepatotoxicity 
Added Potential for Other Lab 
Abnormalities, Embryo Fetal Toxicity 
and Impaired Male Fertility. 
 
To Align with Current 
Investigator Brochure. 
Section 5.5 Dose 
Justification 
Addition of the dose selection and the 
rationale for the decision. 
Updated based on data from the 
primary analysis 
Section 7.1 
GSK2857916 
Treatments 
Administered 
Correction of text related to when 
treatment will be discontinued. 
To align with Section 8.1 
Section 7.2.2 Dose 
Reductions for 
Toxicity 
Table 11 Dose Modification Guidelines 
for GSK2857916 – Related Adverse 
Events  
• removed footnote ‘c’ from table 
 
• Added frequent monitoring of 
platelet count and/or 
neutrophils in the event of a 
Gr3/4 toxicity  
 
 
 
 
 
Administrative - no associated 
footnote related to spot urine 
 
Based on percentage of Gr3-4 
hematologic events it was 
determined that frequent 
monitoring should be 
recommended  
 
 

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Section # and Name Description of Change 
Brief Rationale  
Table 13 Dose Modification Guidelines 
for GSK2857916 Treatment Related 
Corneal Events: 
• Guideline for dose 
modifications amended to 
include symptoms  
 
 
 
 
 
• Updated to remove use of 
prophylactic steroid eye drops 
 
 
 
 
 
• Added statement on 
prescribing additional treatment 
based on ophthalmologist 
discretion 
 
 
 
Updated based on data from the 
primary analysis and 
determination that a participants 
symptoms should also be a 
factor in the determination of a 
dose delay/reduction, and not 
asymptomatic corneal changes.  
 
Removed prophylactic use of 
steroid eye drops based on data 
from the primary analysis 
 
 
Allow flexibility for 
ophthalmologist to prescribe 
appropriate treatment based on 
findings and symptoms reported 
by participant. 
 
 
7.2.3 Corneal 
Supportive Care 
Guidelines and Table 
3 Schedule of 
Activities  
Defined clinically stable relation to eye 
examinations 
To provide additional 
clarification 
7.7.2 Prohibited 
Medications 
Updated guidance on prohibited 
medications 
Changes based on emerging in 
vitro data 
9.1 Efficacy 
Assessments 
Updated language on requirements for 
disease assessments required to be 
completed when confirming disease 
progression. 
Clarification of confirmatory 
disease progression 
assessments 
9.2.8 Pregnancy 
Increased timeframe for contraception 
usage in males and females.  
In May 2019, FDA released 
updated reproductive toxicity 

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Section # and Name Description of Change 
Brief Rationale  
recommendations for oncology 
pharmaceuticals, including 
guidance on labelling the 
duration of contraception 
following cessation of therapy, to 
minimize any potential risk to a 
developing embryo or fetus.  
Inclusion criteria 8&9 not 
updated to align as enrollment 
has closed 
9.2.10.1 Monocular 
Prophylaxis 
Figure 4 Ocular 
Prophylaxis Scheme 
9.2.10.2 Monocular 
Treatment  
Ophthalmologist discretion to utilize 
steroid eye drops added  
Clarification that ophthalmologist 
has discretion to continue 
utilizing steroid eye drops or 
may discontinue 
9.6 Immunogenicity 
Updated text to include requirement for 
PK sample with every ADA sample 
Clarification to emphasize 
existing PK sample requirement 
9.10 Evaluation of 
Anti-Cancer Activity 
Updated timeframe of MRD testing 
Clarification of bone marrow 
(BM) collection for Minimal 
residual disease (MRD) testing 
timeframe. 
 
12.5 Appendix 5: 
Contraception 
Guidance and 
Collection of 
Pregnancy 
Information 
Increased timeframe for contraception 
usage in males and females.  
In May 2019, FDA released 
updated reproductive toxicity 
recommendations for oncology 
pharmaceuticals, including 
guidance on labelling the 
duration of contraception 
following cessation of therapy, to 
minimize any potential risk to a 
developing embryo or fetus.  
Inclusion criteria 8&9 not 
updated to align as enrollment 
has closed 
12.9 Appendix 9: 
GSK Corneal Event 
Severity Scale and 
 
 

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Section # and Name Description of Change 
Brief Rationale  
Mitigation Strategy 
for GSK2857916 
Treatment Related 
Corneal Events  
Table 21: Updated to remove use of 
prophylactic steroid eye drops 
 
 
 
 
 
Table 23: Added 20/15 as a baseline 
vision 
Removed prophylactic use of 
steroid eye drops based on data 
from the primary analysis 
 
 
 
The visual acuity scale did not 
reference vision better than 
20/20. 
 
 

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Amendment 3: 17-DEC-2018 
DOCUMENT HISTORY 
Document 
Date 
Amendment 3-2017N330177_04 
17-DEC-2018 
Amendment 2- (Republishing)- 2017N330177_03 
04-SEP-2018 
Amendment 2- 2017N330177_02 
30-AUG-2018 
Amendment 1- 2017N330177_01 
02-APR-2018 
Original Protocol-2017N330177_00 
18-Jan- 2018 
 
 
Overall Rationale for the Amendment: 
The protocol has been amended to address over-enrollment in the frozen liquid solution 
portion of the study.  
Due to the over-enrollment, the primary analysis will be based on all randomized 
participants (anticipated ~200) enrolled into the frozen liquid solution arms. In addition, a 
sensitivity analysis based on the first 130 participants will be performed to account for 
the original design.  
Section # and Name Description of Change 
Brief Rationale 
All Sections 
Removed references of precise number 
of participants for enrollment  
 
 
To align with actual enrollment  
Section 2 Schedule 
of Activities  
Table 1, footnote 14 Correction of FISH 
testing 
Table 2, Footnote 29 and Table 3 
Footnote 19 window added for patient 
interviews 
Table 4, Footnote 5 clarified  
Typographical error 
To allow greater flexibility for 
interview to occur  
 
Clarification of ocular 
assessment timing 
Section 4 Objectives 
and Endpoints 
Section 1 Protocol 
Synopsis Objectives 
and Endpoints 
Addition of Investigator assessed ORR 
as a secondary objective and endpoint. 
Removed the specification that clinical 
benefit rate (CBR) will be performed by 
IRC assessment  
The primary analysis for the 
endpoint ORR is based on IRC 
assessment. Therefore, a 
secondary analysis for ORR 
based on investigator 
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Section # and Name Description of Change 
Brief Rationale 
described in Section 10.5.1, 
Efficacy Analyses  
Section 5 Study 
Design  
Figure 1 – Study 205678 Schematic 
revised to remove enrollment 
references 
Additional clarification that IA for futility 
is planned for ORR based on 
investigator’s assessment 
Clarification that lyophilized cohort will 
be analyzed separately from 
participants randomized to the frozen 
solution 
Clarification that the final analysis of the 
primary endpoint (ORR) will be 
performed 6 months after the last 
participant is randomized 
To account for possible 
under/over enrollment. 
Clarification of ORR analysis at 
IA and final analysis 
Section 6.1 Inclusion 
Criteria 
Section 1 Protocol 
Synopsis Inclusion 
Criteria 
 
Changed e.g. to i.e. for the 
immunomodulatory agent listed under 
Inclusion criteria 4b 
  
The Latin abbreviation of e.g. 
which translates to “for example” 
and is commonly confused with 
the Latin abbreviation of i.e. 
which translates to “in other 
words”. The intent was that 
participants need to be 
refractory to the 
immunomodulatory agents 
lenalidomide or Pomalidomide 
ONLY (not thalidomide) and 
therefore the correct 
abbreviation is “i.e.” 
 
Section 7 Treatments Added Infusion Time  
Removed text to specify the lyophilized 
cohort will be initiated when enrollment 
has completed in the frozen arms 
To address regulatory 
comments 
 
To more accurately reflect study 
conduct 
Section 9 Study 
Assessments and 
Procedures 
Table 14 Correction of FISH testing 
results  
Typographical error to align with 
Section 7.3, method of treatment 
assignment 

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Section # and Name Description of Change 
Brief Rationale 
Section 9.11.3 
Qualitative 
Telephone Interview 
(Patient Interviews) 
Window added for patient interviews 
Updated to align with Section 2, 
Schedule of Activities 
Section 10.1 
Hypothesis Testing 
Update the timing of final ORR analysis  
Clarification that lyophilized cohort will 
be analyzed separately from 
participants randomized to the frozen 
solution 
To reflect shortened enrolment 
period 
 
Clarification of ORR analysis at 
IA and final analysis 
Section 10.2 Sample 
Size Determination 
Provide updated language on IA and 
final analysis based on sample size of 
100 participants per arm.  
 
To reflect actual enrollment onto 
the frozen liquid solution arms of 
the study  
Section 10.3 Sample 
Size Sensitivity 
Update Table 15 to include power 
scenarios for sample size of 100 
participants per arm.  
 
To accommodate increase in 
sample size due to over 
enrolment. 
Section 10.4 
Populations for 
Analysis 
Add a new analysis population 
(Efficacy), which consist of the first 130 
randomized patients  
To evaluate the effect of over-
enrollment with respect to the 
original planned sample size for 
primary and key secondary 
endpoints. 
Section 10.5.1 
Efficacy Analyses 
Clarifying the analysis population for 
efficacy endpoints at Final analysis  
 
Clarification that IA for futility is planned 
for ORR based on investigator’s 
assessment.  
 
 
To accommodate increase in 
sample size due to over 
enrolment. 
 
 
ORR based on IRC assessment 
is planned for the final primary 
analysis and the IA will be 
performed based on investigator 
assessment.  
Section 10.5.9 
Interim Analyses  
Provide updated language on stopping 
rule/boundary crossing probability for IA 
 

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Brief Rationale 
and final analysis based on sample size 
of 100 participants per arm.  
 
To accommodate increase in 
sample size due to over 
enrolment. 
 
Amendment 2: 04-SEP-2018 
Overall Rationale for the Amendment:  
The protocol has been amended to address feedback from regulatory agencies, EC/IRB, 
and investigators. The updates include the addition of Exclusion Criteria defining the use 
of high dose steroids, clarification of specific timeframe from last treatment required for 
systemic anti-myeloma therapy, and increase of QTcF criteria. Additional PK sampling 
timepoints were added to capture the Cmax of the free cytotoxic drug (cys-mcMMAF) 
and to better define the kinetics of cys-mcMMAF and the elimination phase of ADC and 
cys-mcMMAF. Soluble BCMA collection timepoints were also added to capture the 
effect of GSK2857916 administration on soluble BCMA concentrations over time as a 
marker of pharmacodynamic effect. The dose modifications guidelines for GSK2857916 
related Corneal Events clarify dose adjustments for GSK Scale Grade 2 events. 
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 2 (Republishing) 
04-Sep-2018 
Amendment 2 
30-Aug-2018 
Amendment 1 
02-Apr-2018 
Original Protocol 
18-Jan-2018 
 
Section # and Name 
Description of Change 
Brief Rationale 
All Sections 
Replaced ophthalmologist with 
ophthalmologist (or an optometrist if 
an ophthalmologist is not available) 
 
Updated Investigator Brochure 
Version 
To allow for either an 
optometrist or ophthalmologist 
to perform eye examinations.  
Section 1 Synopsis  
Changed text in Synopsis to reflect 
changes to the text of the protocol 
See below for all significant 
changes 

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Section # and Name 
Description of Change 
Brief Rationale 
Section 2 Schedule of 
Activities (SOA) 
 
Table 1-Table 3: Footnote numbering 
corrected and text made applicable 
for each schedule  
Table 1-Table 3: Abbreviations 
updated  
Table 1: Screening SOA – addition of 
FISH results that are classified as 
high risk beyond the 60-day 
timepoint. 
Table 2: Clarifications of timings for 
vital sign, ECG collections and PK 
sample collection,  
Table 2: Triplicate ECG 
measurements changed from 5 
minutes apart to 2 minutes apart; 
additional timepoints added  
Table 2: Additional PK timepoints 
added 
Table 2 & Table 3: Clarifications of 
timings for imaging added 
Table 2 & Table 3: Clarifications of 
serum and urine immunofixation 
added 
Table 2: Removed requirement for 
German MRI collection for skeletal 
survey 
Table 2: Additional sBCMA sample 
collection timepoints added 
Table 4: Removed requirement for 
mandatory exams in ocular substudy 
Administrative changes and 
clarifications of timepoints  
 
Acceptability of positive results 
for high risk abnormalities by 
FISH have been extended 
beyond 60-days, as those are 
myeloma defining 
abnormalities and do not 
change in the course of the 
disease.  
Additional ECG timepoints 
added to assess at the Cmax 
of the free cytotoxic drug (cys-
mcMMAF) and to detect any 
delayed effects on QTc. 
Additional PK timepoints 
added to capture the Cmax of 
the free cytotoxic drug (cys-
mcMMAF) and to better define 
the kinetics of cys-mcMMAF 
and the elimination phase of 
ADC and cys-mcMMAF. 
Additional sBCMA timepoints 
added to capture the effect of 
GSK2857916 administration 
on soluble BCMA 
concentrations over time as a 
marker of pharmacodynamic 
effect. 
Section 3.4.2 Corneal 
Events 
Added CTCAE grading 
Provides clarity that CTCAE 
scale was utilized to report all 
corneal events in the FTIH 
study. 
Section 4 Objectives 
and Endpoints 
Secondary endpoint for Clinical 
benefit rate added to align with 
Section 1, synopsis 
 
Resolves Discrepancy and 
aligns section to Synopsis  
 
 

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Section # and Name 
Description of Change 
Brief Rationale 
Secondary endpoint for Time to 
Response, Progression Free Survival, 
Time to Progression and Overall 
Survival updated to align with Section 
1, Synopsis and Section 10, 
Statistical Considerations.  
Plasma concentrations of 
GSK2857916 clarified as ADC, total 
mAb, and cys-mcMMAF. 
 
Exploratory Endpoint for MRD 
negativity testing clarified  
Align with Section 10, which 
states all randomized 
participants will be included in 
analyses 
 
 
 
 
 
Clarification on how analyses 
will be performed 
Section 5 Study Design 
 
Study Schema revised to remove 
description of start of lyophilized 
cohort. 
Lyophilized cohort will not 
open until the drug 
configuration is available and 
the enrollment is complete 
under the frozen configuration. 
Section 5.5 Dose 
Justification 
Added CTCAE grading  
Aligned with Section 3.4.2 to 
clarify that the CTCAE scale 
was utilized in the FTIH study  
Section 6.1 Inclusion 
Criteria 
Changed i.e. to e.g. for prior lines 
Table 9 footnote cross-reference 
corrected 
Clarification and Prior Lines of 
therapy updated to clarify it is 
any proteasome inhibitor or 
immunomodulatory agent. 
Section 6.2 Exclusion 
Criteria 
Systemic anti-myeloma therapy 
clarified as excluded if administered 
within ≤14 days or 5 half-lives, 
whichever is shorter 
Added Exclusion criteria #2 for high 
dose steroids 
Modified Exclusion criteria #12 to 
accept malignancy of non-melanoma 
skin cancers 
QTcF increase to 480 msec from 470 
msec 
Exclusion Criteria #1 - 
Clarification of timeframe 
required from last treatment of 
systemic anti-myeloma therapy  
 
Exclusion Criteria #2 added to 
define high dose steroid usage 
that may have anti myeloma 
activity though not given to 
treat the disease 
 
Exclusion Criteria #13 - QTcF 
increased to align with GSK 
internal standards for oncology 

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Section # and Name 
Description of Change 
Brief Rationale 
trials determined by GSK 
Cardiac Safety Panel. 
Section 7 Treatments 
Removed Infusion Time 
Administrative change  
Section 7.2 Dose 
Modifications, Table 13 
Dose Modification 
Guidelines for 
GSK2857916 
Treatment-Related 
Corneal Events 
Table edited for clarity.  
GSK Scale for corneal events 
incorporated and Dosing 
modifications amended  
Changes to dose modifications 
guidelines for GSK2857916 
related Corneal Events further 
clarify dose modifications 
based on the visual acuity or 
findings on ophthalmic 
examination 
Section 7.2.2 Dose 
Reductions for Toxicity 
Dosing delay and restarting language 
added  
Updated to allow for restart 
prior to next cycle in cases 
where the treating physician 
feels it is necessary for 
participants well-being. 
Section 7.2.3 Corneal 
Supportive Care 
Guidelines 
Clarified that corneal supportive care 
is based on GSK Corneal Scale 
(Table 22) 
To provide consistency and 
alignment throughout the 
protocol. 
Section 7.7.2 Prohibited 
Medications 
Caution statement for CYP 
inhibitors/inducers added 
For alignment with IB version 
05, Section 6.4 
Section 7.8 Treatment 
after the End of Study 
Cross-reference corrected from Table 
1 to Table 3 
Administrative change 
Section 8.1 
Discontinuation of Study 
Treatment 
Pregnancy added to the list of 
reasons for discontinuation 
To align with Section 9.2.8 and 
Appendix 5 as animal 
reproductive studies have not 
been conducted with 
GSK2857916 
Section 8.2.5 Corneal 
Event Stopping Criteria 
Added Clarity on use of GSK scale 
and CTCAE scale for reporting 
purposes and dose modifications.  
 
Alignment throughout protocol. 
Both the CTCAE and GSK 
Scale are to be utilized for 
reporting of corneal events and 
clarify that the GSK scale to be 
utilized for dose modification 
decisions.  
Section 9 Study 
Assessments and 
Procedures 
On study visits and PFS follow-up 
visits separated to aligned with SOA 
Tables  
Alignment with Section 2, 
Schedule of Activities  

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Section # and Name 
Description of Change 
Brief Rationale 
 
Table 14 – addition of spot urine 
instructions; and clarification of FISH 
results to align with Section 2, 
Schedule of activities 
Section 9.1 Efficacy 
Assessments 
Clarified language regarding 
collection of PD blood sample 
Language modified to allow for 
confirmation sample to occur 
on the same day as original 
collection.  
Section 9.2 Adverse 
Events 
Added clarity on use of GSK Scale 
and CTCAE  
Added clarity that all AEs will be 
graded using CTCAE and that 
corneal events will also be graded 
using the GSK scale. GSK2857916 
dosing decisions related to 
GSK2857916 corneal events are to 
be made using the GSK Scale for 
corneal events. 
Revised to provide clear 
guidance for dose 
modifications due to 
GSK2857916 corneal events. 
CTCAE scale will be utilized to 
harmonize data with FTIH 
study results 
Section 9.2.1 Time 
Period and Frequency 
for collecting AE and 
SAE information 
Updated AE reporting timeframe from 
30 days to 45 days  
Revised to align with 5 half-
lives of GSK2857916 
Section 9.2.6 Disease 
Related Events and/or 
Disease Related 
Clarified disease progression does 
not need to be reported as an SAE 
Updated to align with GSK 
internal standards for oncology 
trials. 
Section 9.2.7 Adverse 
Events of Special 
Interest 
Added that corneal AESI should be 
graded by CTCAE and GSK Scale for 
corneal events 
Revised to align with Section 
9.2 Adverse Events. 
Section 9.2.9 Ocular 
Exams and Procedures 
Added statement to clarify 
representative images will be 
collected and stored centrally. 
Revised to align with all 
GSK2857916 protocols 
Section 9.2.10.1 
Monocular Prophylaxis 
Preservative free artificial tear 
requirements updated to align with 
Table 21, Prophylactic measures for 
corneal events associated with 
GSK2857916 
Clarification to align with Table 
21. 

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Section # and Name 
Description of Change 
Brief Rationale 
Section 9.2.10.3 Sub-
Study Exams 
Clarification of exam requirements  
Updated information regarding 
confocal exams. 
Section 9.4.2 ECOG 
Performance Status  
Timepoints updated to perform to 
align with Section 2, Schedule of 
Activities  
Clarification to align with 
Section 2. 
Section 9.4.4 
Electrocardiogram  
Triplicate ECG measurements 
changed to 2 minutes apart 
Allows time for EOI PK sample 
collection 
Section 10.2 Sample 
Size Determination  
 Update the type-1 error and power 
due to the change in boundary for 
claiming efficacy at final ORR 
analysis. 
To address EMA’s comments 
on maintaining overall type-1 
error (1-sided 2.5%) adjusting 
for multiplicity (two dose arms), 
the boundary for claiming 
efficacy at final ORR analysis 
was modified. 
Section 10.3 Sample 
Size Sensitivity  
Update scenarios due to change in 
boundary for claiming efficacy at final 
ORR analysis. 
To address EMA’s comments 
on maintaining overall type-1 
error (1-sided 2.5%) adjusting 
for multiplicity (two dose arms), 
the boundary for claiming 
efficacy at final ORR analysis 
was modified. 
Section 10.4 
Populations for Analysis  
Provide reference for detailed 
definition of Evaluable Population, 
which will be used for ORR analysis 
at interim 
To ensure consistency with 
IDMC charter 
Section 10.5.1 Efficacy 
Analyses  
 
Update language regarding ORR 
(confirmed vs. unconfirmed) at interim 
analysis. 
Clarify that the ORR analysis 
at interim should be based on 
confirmed response if 
available. 
Section 10.5.2 Safety 
Analysis  
Table 18 
Addition of summarizing corneal 
events using GSK Scale for corneal 
events 
To clarify that AESI of corneal 
events will also be 
summarized using the GSK 
Scale for corneal events. 
Section 
10.5.4.1Pharmacokinetic 
Data Analyses 
Creation of subsections in Section 
10.5.4 to separate pharmacokinetic 
and statistical analyses 
For clarity 
Added noncompartmental 
analysis based on revised PK 
sampling schedule 

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Section # and Name 
Description of Change 
Brief Rationale 
Addition of non-compartmental 
analysis, data permitting 
Section 10.5.4.2 
Statistical Analysis of 
Pharmacokinetic Data 
Creation of subsections in Section 
10.5.4 to separate pharmacokinetic 
and statistical analyses 
For clarity 
Section 10.5.9 Interim 
Analyses 
Modify boundary of claiming efficacy 
at final ORR analysis, and associated 
operating characteristics. 
To address EMA’s comments 
on maintaining overall type-1 
error (1-sided 2.5%) adjusting 
for multiplicity (two dose arms), 
the boundary for claiming 
efficacy at final ORR analysis 
was modified. 
Section 11 References 
GSK2857916 IB version updated 
from 03 to 05  
Updated to include most 
recent version of IB 
Section 12.5 
Contraception Guidance 
New template language added to 
elective termination description 
Clarifies notification needed 
“for medical reasons” 
Section 12.7 Liver 
Chemistry Stopping 
Criteria 
Removed non-applicable PK sample 
statements in footnote 6 
 
PK collection interval updated to 5 
half-lives 
Comparator language 
removed since monotherapy 
study 
Clarification  
Updated timeframe during 
which drug concentrations 
should be measured 
12.9 Corneal Event 
Severity Grading and 
Mitigation Strategy 
Table 22 
Added clarification that Grading is a 
GSK Scale  
Footnotes updates  
To align with Section 9.2 
Adverse Events and to indicate 
the GSK Scale for corneal 
events is not a CTCAE scale 
12.10 Modified Diet in 
Renal Disease (MDRD) 
Formula 
MDRD formula for calculating the 
estimated glomerular filtration rate 
was clarified to show superscript 
values 
Provides instruction for 
calculation of eGFR 
12.12 Appendix 12 
Table 24 clear version inserted 
Modified description of simulation 
studies for evaluating operating 
characteristics  
The numbers in the Table 24 
in previous version were not 
legible. 
To clarify the objectives and 
conduct of simulation studies 

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Section # and Name 
Description of Change 
Brief Rationale 
Throughout 
Minor editorial and document 
formatting revisions 
Minor, therefore have not been 
summarized 
 
Amendment 1: 02 April 2018 
Overall Rationale for the Amendment:  
The protocol has been amended to address regulatory agency advice. The original single-
arm design with 1 dose level (3.4 mg/kg GSK2857916 Q3W) was amended to an 
open-label, randomized, 2-arm study with 2 dose levels by including the 2.5 mg/kg Q3W 
dose. In addition, a new exploratory cohort of 25 participants, who will receive a 
lyophilized configuration of GSK2857916, has been added to gain clinical experience 
with the lyophilized configuration. To accommodate these main changes, the overall 
sample size and related analytical methods have been changed. 
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 1 
02-Apr-2018 
Original Protocol 
18-Jan-2018 

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Section # and Name 
Description of Change 
Brief Rationale 
Cover Page 
 
Study title updated 
A Phase II, Open Label, 
Randomized, Two-Arm Study to 
Investigate the Efficacy and Safety 
of Two Doses of the Antibody Drug 
Conjugate GSK2857916 in 
Participants with Multiple Myeloma 
Who Had 3 or More Prior Lines of 
Treatment, Are Refractory to a 
Proteasome Inhibitor and an 
Immunomodulatory Agent and Have 
Failed an Anti-CD38 Antibody 
(DREAMM 2). 
Title updated to reflect the 
design change (see below) 
Synopsis  
Changed text of Synopsis to reflect 
changes to the text of the protocol 
See below for all significant 
changes 
All sections 
Replaced the word ‘patient’ with 
‘participant’ and ‘subset’ replaced 
with ‘sub-study’. 
New references added 
 
Section 2 Schedule of 
Activities 
 
 
 
Separate schedule tables for 
Screening assessments, on study 
assessment, ‘end of treatment 
assessment and follow-up 
assessment have been included. 
Deletion of coagulation criteria 
(INR) for determining adequate 
organ system function 
Removal of aspirate for flow 
cytometry  
Added PET/CT to confirm CR, sCR 
 
German exceptions to PET/CT 
The tables have been separated 
to clarify activities.  
 
 
Current liver event management 
guidelines do not require INR.  
Flow cytometry is not used in 
IMWG Kumar, 2016. 
Based on Kumar, 2016.  
Germany: approval by the 
German Federal Office for 
Radiation Protection is required 
prior to PET/CT or other x-rays 
can be performed. 

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Section 3.1 Study 
Rationale  
 
Section 3.4.2 Corneal 
Events 
Section 3.4.3 
Pharmacokinetics 
Section 3.5.3 Overall 
Benefit- Risk 
Conclusions 
Ongoing FTIH study number has 
been changed from BMA117158 to 
BMA117159 
Additional information regarding 
corneal toxicity included 
Included new section 
‘Pharmacokinetics; with section 
number 3.4.3 
Overall Benefit-Risk conclusions is 
updated to reflect the additional 
dose. 
Editorial changes 
 
 
 
To support the additional arm 
that includes dose level 
2.5mg/kg 
Updated to reflect the change in 
study design. 
Section 4 Objectives 
and Endpoints, 
Primary Objective 
 
 
Exploratory Objective 
 
 
 
 
Ocular Sub-Study 
Objective 
 
Primary objective has been 
modified: to evaluate the clinical 
efficacy of 2 doses of GSK2857916 
in participants with 
relapsed/refractory multiple 
myeloma by overall response rate 
 
New exploratory endpoint has been 
included: To assess the safety, 
efficacy, immunogenicity, and 
pharmacokinetics of GSK2857916 
in a lyophilized configuration (n=25) 
 
Number of participants to evaluate 
the effect of topical corticosteroids 
on corneal findings has been 
increased to 30 (15 in each dose 
arm). 
Updated to reflect the change in 
study design.  
 
 
To gain clinical experience with 
the lyophilized configuration.  
 
 
 
Number increased to reflect the 
additional arm and increased 
study sample size.  
Section 5 Study 
Design 
 
Study design description and the 
Study Schema revised. 
 
Efficacy and safety results from the 
interim analysis will not be shared 
with investigators or other study/site 
personnel 
Language and the schema 
modified to clarify changes in 
study design have been added, 
including the addition of a 
second arm, change to the total 
number of participants, IA to 
assess futility, IDMC to review 
IA results, and an additional 
cohort of participants (n=25) 
who will receive the lyophilized 
configuration.  

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Section 5.2 Number of 
Participants 
 
Number of participants to be 
screened has been changed from 
100 to 170, to be enrolled changed 
from 90 to 155 and number of 
recruitment centers changed from 
30 to 60 investigational sites. 
Number of participants in the ocular 
sub-study increased to 30 
Study design has changed from 
1 arm to 2 arms, thus the 
sample size is increased. Ocular 
sub-study sample size is 
increased for same reason. 
Section 5.3 Participant 
and Study Completion 
 
Definition of the study-completed 
participant has been modified 
New criteria have been added: If a 
participant remains on treatment at 
the time end of study is achieved, 
they will be offered an option to 
extend treatment on this or another 
protocol. 
Language to offer participants 
this option was inadvertently 
omitted.  
 
Section 5.4: Scientific 
Rationale of Study 
Design 
Section 5.5: Dose 
Justification 
Scientific rationale and dose 
justification sections are updated.  
Scientific rationale and dose 
justification updated to address 
new design and additional dose 
level. 
Section 6.2 Exclusion 
Criteria 
 
Deletion of exclusion criterion #3 
regarding best corrected visual 
acuity 
New #2 Exclusion criteria for 
symptomatic amyloidosis, active 
‘polyneuropathy, organomegaly, 
endocrinopathy, myeloma protein, 
and skin changes’ (POEMS) 
syndrome, active plasma cell 
leukemia at the time of screening 
and Prior allogeneic stem cell 
transplant has been added. 
#3 Per regulatory agency 
suggestion, the criterion related 
to visual acuity limitations 
deleted. Requirement for 
preexisting conditions has been 
revised according to feedback 
for regulatory agencies. 
New # 2 Included to avoid 
unpredictable toxicity. 
Section 7 Treatments 
 
Table listing the study treatments. 
 
 
To provide details of how the 
lower dosage form and the 
lyophilized form are supplied to 
the sites. 
Section 7.2.2 Dose 
Reductions for 
Toxicity 
Table 10 
Permitted dose reductions have 
been included. Table 10 updated. 
Dose reductions updated per 
design change to 2 dose levels.  

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Section 7.2.2 Dose 
Reductions for 
Toxicity 
Table 13 
Modified grading of corneal events 
by deleting the presence of 
asymptomatic corneal findings on 
ophthalmic exam not observed at 
baseline (grade 1) 
 
 
 
 
Modified management of corneal 
events, i.e. dosage of preservative 
free artificial tears has been 
increased for G4 corneal events. 
Footnote ‘c’ regarding patients with 
prior allogenic transplant with 
corneal toxicity has been deleted: 
As the AE grading scale is now 
based on corneal clinical 
symptoms and visual acuity, this 
situation (asymptomatic 
findings) is no longer applicable 
as all findings will be considered 
AEs. Changes made due to 
regulatory agency 
recommendations. 
Editorial changes to clarify that 
artificial tears are to be 
increased for other AE grades. 
 
Editorial changes to reflect prior 
allogenic transplants are now 
excluded, thus footnote is 
unnecessary. 
Section 7.3 Method of 
Treatment 
Assignment  
 
Section 7.3 updated for 
randomization and stratification 
information for treatment 
assignment. 
 
7.3 changes address 
randomizing to 2 arms. 
Section 8.1 
Discontinuation of 
Study Treatment 
Deletion of language that allowed 
participants who have achieved CR 
to discontinue treatment. 
Decision made to treat all 
patients until PD  
Section 8.2.5 Corneal 
Supportive Care 
Guidelines 
Management guidelines for corneal 
events updated. 
Guidelines updated according to 
feedback from regulatory 
agency. 
Section 8.2.6  
Language added to reference Table 
11 
 
 
Added to reinforce the actions 
based on a Grade 4 IRR.  

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Section 9 Study 
Assessments and 
Procedures 
Section 9.2 Adverse 
Events 
 
 
Baseline demographic assessment 
and medical family history 
assessment included 
General language corrections made 
for clarity. 
Adverse event coding by MedDRA 
and grading by NCI-CTCAE 
included 
Editorial updates: demographics 
and medical history were added.  
 
Section 9.1 Efficacy 
Assessment 
IgG, IgM and IgA assessments and 
additional bone marrow testing 
included 
To provide additional 
clarification  
Section 9.2.10 Ocular 
Sub-Study 
Examination 
The language in the Ocular Sub-
Study Examinations section has 
been updated for increased clarity 
The language in Ocular Sub-study 
examinations now modified to 
remove confrontation of visual 
fields, evaluation of optic nerve and 
retina. Tear film examination, 
anterior segment photography, and 
pachymetry were added. Fundus 
and anterior segment photography 
are now included at baseline, end 
of study, and last follow-up visit. 
Language modified to clarify the 
required examinations and 
palliative treatment for 
participants in this cohort. 
Recommendations from 
independent corneal experts.  
9.2.10.1 Monocular 
Prophylaxis 
9.2.10.2 Monocular 
Treatment 
9.2.10.3 Sub-Study 
Exams 
Registration into RAMOS after 
assessment completion deleted. 
Additional information and 
schematic for prophylactic eye 
drops included. 
The section for monocular 
prophylaxis has been updated to 
clarify the treatment.  
9.2.9 (old) 
The section on assessment of 
sentinel events deleted.  
Removed as this information is 
specific to a GSK process rather 
than something the sites must 
do. This will be captured in the 
SRM.  

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Section 9 
Table 14 List of 
Clinical Laboratory 
Tests 
 
Total carbon dioxide replaced with 
bicarbonate 
Bone marrow to confirm stringent 
complete response by flow 
cytometry deleted and an additional 
footnote included 
Editorial changes to reflect the 
correct parameter 
 
Editorial changes to reflect 
IMWG criteria 2016. 
9.9.1 sBCMA Sample 
Analysis 
 
Specific assay used for sample 
collection, i.e. 
electrochemiluminescent 
immunoassay deleted 
 
9.10 Evaluation of 
Anti-Cancer Activity 
Testing for evaluation of anti-cancer 
activity at 6 months included 
 
Clarification to state this should 
be performed at the 6-month 
timepoint.  
Section 10.1 
Hypothesis Testing 
 
The sample size and hypothesis 
testing is updated to reflect a 2-arm 
study. Updated enrollment duration 
and number of evaluable 
participants for interim analysis. 
 
Section updated to reflect 
revised design and operating 
characteristics based on 
interactions with regulatory 
agency. 
Section 10.2 Sample 
Size Determination 
Included information on 
independent cohort for lyophilized 
configuration. 
Section updated to reflect 
revised design and operating 
characteristics based on 
interactions with regulatory 
agency. 
Section 10.3 Sample 
Size Sensitivity 
Section 10.5.9.1 
Futility Stopping Rule 
based on Group 
Sequential Design 
Updated IA futility stopping rules 
Section updated to reflect 
revised design and operating 
characteristics based on 
interactions with regulatory 
agency. 
Section 10.4 
Population for 
Analysis 
Section 10.5.1 
Efficacy Analysis 
Safety population has been 
replaced with ITT population as a 
primary population of analysis of 
efficacy data and safety population 
updated to be used for analysis of 
clinical safety data 
 
Section 10.5.1 
Efficacy Analysis 
Updated statistical analysis 
methods for efficacy endpoints  
 

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Section 10.5.9.2 
New section heading “Additional 
Comparative Futility Stopping Rule 
Based on Bayesian Approach” 
added 
Clarification of the posterior 
probability calculations are 
added 
Section 12.4 Adverse 
Events: Definition and 
Procedures for 
Recording, 
Evaluating, Follow-up 
and Reporting  
AE reporting corrected. 
. 
Reporting based on CT-CAE 
grading.  
 
Section 12.7.1.2 
References 
Additional relevant references 
included 
 
Section 12.8 
Appendix 8 deleted 
IMWG response criteria are 
referenced directly. Further 
interpretation is not needed. 
12.10 Corneal Event 
Severity Grading and 
Mitigation Strategy 
Table 21, Table 22 and Table 23 
updated 
Reporting based on CT-CAE 
grading.  
Table 22 (Corneal events AE 
grading scale) is now based on 
best corrected visual acuity.  
 

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11.12. 
Appendix 12: Statistical Considerations for Section 10.5.9.2 
Additional Comparative Futility Stopping Rule Based on 
Bayesian Approach 
Introduction 
This document provides details about the additional comparative futility stopping rule 
based on the Bayesian approach at interim analysis (IA) for Study 205678.  
As described in Section 9.5.9.2, the additional comparative rule based on the Bayesian 
approach will be used to further facilitate the decision of early stopping for futility. The 
arm deemed inferior to the other will be dropped. In practice, if both arms pass the futility 
boundaries based on group sequential design described above, posterior probability of 
observing a better RR in one arm relative to the other will be calculated. If such a 
probability is at least 90%, then the treatment arm with lower RR will be dropped due to 
lack of efficacy. To calculate the posterior probability, a non-informative beta prior 
(0.025,0.1) will be used for each arm.  
 
Statistical Modeling  
In the Bayesian approach,  
let P1 denote the response rate for arm 1; m1 and X1 denote the number of participants and 
number of responders at IA for arm 1;  
let P2 denote the response rate for arm 2; m2 and X2 denote the number of participants and 
number of responders at IA for arm 2; 
We assume P1 and P2 are independent. 
We assume the prior distributions of response rates 
 and 
 follow a beta 
distribution beta (,). The beta distribution represents the prior knowledge or belief 
about the efficacy of the new drug. The quantity 
 reflects the prior mean response 
rate, while the quantity  +  reflects the amount of information contained in the prior. 
The larger value of  +, the stronger belief the prior has. In both simulations and actual 
IA, a non-informative beta prior (0.025,0.1) will be used for each arm. 
We assume 
 and 
 
Consequently, the posterior distributions of the response rates P1 and P2 follow beta 
distributions: 
P1|x1~beta(+ x1, + m1 - x1), P2|x2~beta(+ x2, + m2 – x2). P1|x1 and P2|x2 are also 
independent.  
The comparative futility stopping rules are defined as: 

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If the posterior probability P (P1 > P2|x1, x2) > 97.5%, then arm 2 is considered inferior to 
arm 1 and will stop for futility.  
If the posterior probability P (P2 > P1|x1, x2) > 97.5% 𝑃(𝑃2 > 𝑃1|𝑥1, 𝑥2) > 90%, then 
arm 1 is considered inferior to arm 2 and will stop for futility. 
Let 1*= + x1, 1*= + m1 - x1, 2*= + x2, 2*= + m2 – x2, 
Following the methods of [Dmitrienko, 2006], the posterior probabilities P (P1 > 
P2|x1,x2) and P (P2 > P1|x1, x2) will be computed as  
 
 
Where 
 and 
 are the cumulative distribution functions of B(α1*,β1*) 
andB(α2*,β2*) distributions, respectively. The integral on the right-hand side of this 
equation was computed using the integrate function in R.  
 
Determination of the Cutoff for Posterior Probabilities. 
The cutoff for posterior probabilities was chosen as 97.5%, to allow for dropping an arm 
with substantially inferior response rates (e.g absolute difference > 28%). The posterior 
probabilities of (Arm 1 Response Rate > Arm 2 Response Rate) for all possible scenarios 
of the comparative rule at IA are shown in Table 24. 
Table 24 
Posterior Probabilities of (Arm 1 Response Rate > Arm 2 Response 
Rate) at Interim Analyses 
 
Note: For both Arm 1 and Arm 2, the IA sample sizes are assumed to be 25. The green cells represent scenarios with 
posterior probabilities greater than 97.5%.  
 
 

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Evaluating Probabilities of Stopping for Futility Using Simulations 
Simulation studies are conducted to evaluate probabilities of stopping for futility at the 
interim and claiming efficacy at final using both futility rules (group sequential design 
and Bayesian approach). Scenarios of simulation studies tested are listed in Table 25. 
Table 25 
Scenarios of Simulation Studies to Evaluate Probabilities of 
Stopping for Futility 
Scenarios 
Response Rate 
Arm 1 
Arm 2 
1 
33% 
60% 
2 
33% 
45% 
3 
33% 
33% 
4 
33% 
25% 
5 
33% 
20% 
6 
33% 
15% 
7 
33% 
10% 
8 
15% 
15% 
 
For each scenario, K=10,000,000 trials are simulated based on the assumed response 
rates (RR) for each arm (assuming number of responders for both arms follow binomial 
distribution). IA and final sample sizes are fixed as 25 and 65, respectively. For each 
simulate trial, the posterior probabilities 
 and 
 are 
compute as specified above. For each simulated trial, both futility rules will be used to 
determine whether the trial should stop for futility at IA or claim efficacy at final. Such 
probabilities will be computed based on K=10,000,000 simulated trials. The simulation 
results are summarized in Table 20 in Section 9.5.9.2. 
References 
Dmitrienko A, Wang MD. Bayesian predictive approach to interim monitoring in clinical 
trials. Statistics in Medicine. 2006 July 15;25(13):2178-2195. 
 
 
 

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11.13. 
Appendix 13: 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 1.2) and include:  
• Collection of blood and urine samples including:  
o Safety assessments which may include routine blood and urine 
sampling 
o Efficacy assessments to be sent to central lab 
• Measurement of vital signs (BP, heart rate, body temperature). 
• Identification and reporting of concomitant medications. 
• Patient reported signs and symptoms, or abnormalities noted based on vital 
signs are reported to the Principal Investigator to determine if they meet the 
definition of an 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. 
 

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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 
care specialist clinic.  
All protocol specific assessments should be completed by the alternative eye care 
specialist at the clinic. Activities that may be done as part of in-home eye exams, must 
follow the schedule provided in the SoA (Section 1.2) and include:  
• Best Corrected Visual Acuity, or Visual Acuity (VA) by near-chart visual 
acuity/pinhole. 
• Slit lamp exam  
• Intraocular pressure measurement & time checked  
• Dilated funduscopic exam  
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. 
• 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. 

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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 
remote PRO Administrator will create a data change form with the participants’ 
responses and send to the third party vendor for the study to add to the study portal.  
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. 
 
 
 
 

Signature Page for  205678 TMF-16142696 v1.0
Signature Page for TMF-16142696 v1.0
Reason for signing: Approved
Name: 
Role: Approver
Date of signature: 06-Jul-2023 16:46:15 GMT+0000
PPD