Clinical trial NCT04177823
Conditions: Multiple Myeloma
Keywords: belantamab mafodotin DLT RRMM
Sponsor: GlaxoSmithKline
Start date: 2019-12-09; Completion date: 2021-12-30
Enrollment: 6 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Multiple myeloma (MM) is a neoplastic plasma cell disorder that is characterized by osteolytic bone lesions, anemia, hypercalcemia and renal failure. belantamab mafodotin was well tolerated in previous studies with at least one dose of belantamab mafodotin in heavily pre-treated participants with relapsed/refractory multiple myeloma (RRMM). This aim of the study is to explore safety, pharmacokinetics (PK), tolerability, immunogenicity and clinical activity of belantamab mafodotin monotherapy in Chinese participants with RRMM who have received at least 2 prior line of anti-myeloma therapy including an alkylator, a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD). This study will include two dose cohorts 2.5 milligram per kilogram (mg/kg) and 3.4 mg/kg. A maximum of 12 participants will be enrolled, 6 each for 2.5 mg/kg cohort and 3.4 mg/kg cohort based on 3+3 design. Participants will be treated until disease progression, intolerable toxicity, end of study or informed consent withdrawal.

Detailed description:

Arms: arm 1: Participants will be administered belantamab mafodotin 2.5 mg/kg or 3.4 mg/kg as an intravenous infusion on Day 1 of each 21-day cycle over 30 minutes. Participants will be treated until disease progression, intolerable toxicity, end of study or informed consent withdrawal.
Interventions: intervention 1: Belantamab mafodotin
Intervention descriptions: intervention 1: Belantamab mafodotin will be available as lyophilized powder 100 mg/vial in single-use vial for reconstitution. It will be administered at a calculated dose of 2.5 mg/kg or 3.4 mg/kg as an IV infusion on Day 1 of each cycle over 30 minutes.

Protocol documents:
Prot_000.pdf: 
TMF-14065056 
CONFIDENTIAL 
208465 
GlaxoSmithKline group of companies 
 
Protocol Amd 03 
 
1 
 
TITLE PAGE 
Protocol Title: A Phase I Open-label, Dose Escalation Study to Investigate the Safety, 
Tolerability, Pharmacokinetics, Immunogenicity and clinical activity of the Antibody 
Drug Conjugate belantamab mafodotin in Chinese Participants with Relapsed/Refractory 
Multiple Myeloma Who Have Failed At Least Two Lines of Previous Treatment, 
Containing an alkylator, a Proteasome Inhibitor and an Immunomodulatory Agent 
Protocol Number: 208465/Amendment 3 
Compound Number: 
GSK2857916 
Study Phase: Phase 1 
Short Title: Phase I dose escalation study of belantamab mafodotin in Chinese 
participants with relapsed/refractory multiple myeloma 
Acronym: CDREAMM 1 
 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Medical Monitor Name and Contact Information  
This information will be provided in the Study Reference Manual (SRM). 
Regulatory Agency Identifying Number(s): Not applicable  
Approval Date: 26-OCT-2021 
 
 
 
Copyright 2021 the GlaxoSmithKline group of companies. All rights reserved. 
Unauthorised copying or use of this information is prohibited. 
 


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SPONSOR SIGNATORY: 
 
Protocol Title: A Phase I Open-label, Dose Escalation Study to Investigate the Safety, 
Tolerability, Pharmacokinetics, Immunogenicity and clinical activity of the Antibody 
Drug Conjugate belantamab mafodotin in Chinese Participants with Relapsed/Refractory 
Multiple Myeloma Who Have Failed At Least Two Lines of Previous Treatment, 
Containing an alkylator, a Proteasome Inhibitor and an Immunomodulatory Agent 
Protocol Number: 208465/Amendment 3 
Compound Number: 
GSK2857916 
 
 
 
 
 
 
Beulah Ji 
VP & Head of Development, GSK China  
 
Date 
 
 
 
The signed page is a separate document. 
 
 


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DOCUMENT HISTORY 
List dates of original protocol and all amendments in reverse chronological order. 
Document 
Date 
DNG Number 
Amendment 3 
26-Oct-2021 
TMF-14065056 
Amendment 2 
30-Oct-2020 
2018N359597_02 
Amendment 1 
02-Nov-2019 
2018N359597_01 
Original Protocol 
01-Apr-2019 
2018N359597_00 
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Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1. Synopsis 
Section 5.1. Inclusion 
criteria 
Inclusion criteria 8 and 9: Updated the 
period to use contraception (Female: 4 
months after last dose of belantamab 
mafodotin; Male: 6 months after last dose of 
belantamab mafodotin) 
Updated based on current 
safety information 
Section 1.3. Schedule of 
Activities (SoA) 
Updated footnote 19 and 33 
- Samples for pharmacokinetics will be 
collected for the interpretation of ADA 
results one year after the first dose of last 
subject 
- Samples for 
 will be 
collected up to one year after last subject 
first dose 
As the sample for 
pharmacokinetic analysis 
and 
 will not be 
collected further.  
Section 2.2. Background 
Current treatment landscape for treating 
Relapsed/Refractory Multiple Myeloma 
(RRMM) in China 
Updated based on latest 
information available 
Section 2.3.3. 
Pharmacokinetics and 
Pharmacodynamics 
Pharmacokinetic and Pharmacodynamic 
information updated 
Updated to align with 
current IB information 
Section 2.4.1. Risk 
Assessment 
Update in explanation of risks   
To align with IB update 
Section 2.4.3. Overall 
benefit: Risk conclusion 
Removed the clinical experience available 
from the study BMA117159 
Based on current safety 
information 
Section 3. Objectives and 
Endpoints 
Added exploratory objective and endpoint 
for
assessment 
To align with Schedule of 
activities table 
CCI
CCI
CCI


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Section # and Name 
Description of Change 
Brief Rationale 
Section 4.1. Overall Design 
Section 4.4. End of study 
Updated or added the definition of End of 
study (EOS) 
To make it align with other 
study protocols in 
oncology 
Section 6.6. Dose 
modification 
Updated Table 5 Dose Modification 
Guidelines for Belantamab Mafodotin-
Related Adverse Events.  
- Added row for ‘Urine Dipstick’.  
- For thrombocytopenia separate 
recommendations are made for 
Belantamab Mafodotin during grade 3 
and grade 4 toxicity 
- For Neutropenia, recommendations for 
Belantamab Mafodotin are updated 
according to current available information 
- For Pneumonitis, recommendations for 
Belantamab Mafodotin for Grade 2 and 
Grade 3-4 toxicities are updated 
according to current available information 
Updated based on current 
information on BCMA 
Section 7.1. Dose 
modification 
Added a point that study treatment may be 
permanently discontinued at ‘Investigator’s 
discretion’.  
Added for clarity 
Previous Sections 7.1.2. 
QTc Stopping Criteria 
 
Deleted 
Based on available data, 
cardiac risk was 
determined to be low and 
stopping criteria were 
removed 
Previous Sections 
7.1.4. Left Ventricular 
Ejection Fraction (LVEF) 
Stopping criteria 
Deleted 
Based on available data, 
cardiac risk was 
determined to be low and 
routine monitoring 
was removed 
Section 8.3.1. Time Period 
and Frequency for 
Collecting AE and SAE 
Information 
SAE and AE collection period has been 
updated from 45 days to 70 days after the 
participant is discontinued from the study 
treatment. 
Updated as per current 
safety information 
Section 9.4.9. Clinical 
Activity Analyses 
Added
assessment 
To align with updated 
objective and endpoint 
Section 9.5. Interim 
Analyses 
Updated end of study definition 
To align with updated 
EOS definition in Section 
4.4 
Section 11.2. Appendix 2. 
Clinical Laboratory Tests 
Added point number 6, on use of urine 
dipstick to assess for presence of urine 
protein 
Added for clarity 
Section 11.4. Appendix 4. 
Contraceptive Guidance and 
Collection of Pregnancy 
Information 
Under heading: Collection of Pregnancy 
Information. The duration is updated from 
5 months to 6 months for pregnancy 
information of a female partner of a male 
study participant following last dose of study 
treatment.  
 
Updated according to 
current safety information 
CCI


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Section # and Name 
Description of Change 
Brief Rationale 
The duration is updated from 8 months to 
4 months for pregnancy information of a 
female study participant following last dose 
of study treatment. 
Whole document 
Minor editorial, alignment for consistency 
and document formatting revisions 
Minor, therefore not been 
summarized 
 


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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3 
1. 
PROTOCOL SUMMARY ........................................................................................ 10 
1.1. 
Synopsis ..................................................................................................... 10 
1.2. 
Schema ...................................................................................................... 17 
1.3. 
Schedule of Activities (SoA) ........................................................................ 18 
2. 
INTRODUCTION .................................................................................................... 24 
2.1. 
Study Rationale .......................................................................................... 24 
2.2. 
Background ................................................................................................ 24 
2.3. 
Human Experience with Belantamab Mafodotin .......................................... 26 
2.3.1. 
Clinical studies ............................................................................. 26 
2.3.2. 
Safety .......................................................................................... 27 
2.3.3. 
Pharmacokinetics and Pharmacodynamics .................................. 28 
2.4. 
Benefit/Risk Assessment ............................................................................ 30 
2.4.1. 
Risk Assessment ......................................................................... 31 
2.4.2. 
Benefit Assessment ..................................................................... 37 
2.4.3. 
Overall Benefit: Risk Conclusion .................................................. 37 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 37 
4. 
STUDY DESIGN .................................................................................................... 38 
4.1. 
Overall Design ............................................................................................ 38 
4.1.1. 
Planned Dose Levels ................................................................... 39 
4.1.2. 
Dose-Limiting Toxicity .................................................................. 40 
4.1.2.1. 
Completion of Dose Escalation ................................... 40 
4.2. 
Scientific Rationale for Study Design .......................................................... 40 
4.3. 
Justification for Dose .................................................................................. 41 
4.3.1. 
Belantamab Mafodotin Starting Dose Justification ....................... 41 
4.4. 
End of Study Definition ............................................................................... 42 
5. 
STUDY POPULATION ........................................................................................... 42 
5.1. 
Inclusion Criteria ......................................................................................... 42 
5.2. 
Exclusion Criteria ........................................................................................ 45 
5.3. 
Lifestyle Considerations .............................................................................. 46 
5.4. 
Screen Failures........................................................................................... 46 
6. 
STUDY TREATMENT ............................................................................................ 47 
6.1. 
Study treatment(s) Administered ................................................................. 47 
6.1.1. 
Belantamab Mafodotin Treatments Administered ......................... 47 
6.2. 
Preparation/Handling/Storage/Accountability .............................................. 48 
6.3. 
Measures to Minimise Bias: Randomization and Blinding ........................... 48 
6.4. 
Study treatment Compliance ....................................................................... 48 
6.5. 
Concomitant Therapy.................................................................................. 49 
6.5.1. 
Permitted Medication(s) ............................................................... 49 
6.5.2. 
Prohibited Medication(s) .............................................................. 49 
6.5.3. 
Prohibited Device(s) .................................................................... 50 
6.6. 
Dose Modification ....................................................................................... 50 


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6.6.1. 
Corneal Supportive Care Guidelines for Belantamab 
Mafodotin ..................................................................................... 55 
6.7. 
Intervention after the End of the Study ........................................................ 57 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 57 
7.1. 
Discontinuation of Study Treatment ............................................................ 57 
7.1.1. 
Liver Chemistry Stopping Criteria ................................................ 58 
7.1.1.1. 
Study treatment Restart or Rechallenge after 
liver stopping criteria met ............................................ 59 
7.1.2. 
Allergic and Anaphylactic Reaction Stopping Criteria ................... 60 
7.1.3. 
Stopping Criteria Based on Ocular Examination Findings ............ 60 
7.1.4. 
Infusion-Related Reaction Stopping Criteria ................................ 60 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................... 60 
7.3. 
Lost to Follow Up ........................................................................................ 60 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 61 
8.1. 
Efficacy Assessments ................................................................................. 63 
8.2. 
Safety Assessments ................................................................................... 64 
8.2.1. 
Physical Examinations ................................................................. 64 
8.2.2. 
Vital Signs .................................................................................... 64 
8.2.2.1. 
First Infusion ............................................................... 64 
8.2.2.2. 
Subsequent Infusions ................................................. 64 
8.2.3. 
Electrocardiograms ...................................................................... 64 
8.2.4. 
Echocardiogram........................................................................... 65 
8.2.5. 
Clinical Safety Laboratory Assessments ...................................... 65 
8.2.6. 
ECOG Performance Status .......................................................... 65 
8.2.7. 
Visual Function Questionnaire ..................................................... 65 
8.2.7.1. 
The Ocular Surface Disease Index ............................. 66 
8.3. 
Adverse Events and Serious Adverse Events ............................................. 66 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 66 
8.3.2. 
Method of Detecting AEs and SAEs ............................................. 67 
8.3.3. 
Follow-up of AEs and SAEs ......................................................... 67 
8.3.4. 
Regulatory Reporting Requirements for SAEs ............................. 67 
8.3.5. 
Pregnancy ................................................................................... 67 
8.3.6. 
Cardiovascular and Death Events ................................................ 68 
8.3.7. 
Disease-Related Events and/or Disease-Related 
Outcomes Not Qualifying as SAEs............................................... 68 
8.3.8. 
Adverse Events of Special Interest .............................................. 68 
8.3.9. 
Ocular Examinations and Procedures .......................................... 69 
8.4. 
Treatment of Overdose ............................................................................... 69 
8.5. 
Pharmacokinetics ....................................................................................... 70 
8.5.1. 
Blood Sample Collection for Pharmacokinetics ............................ 70 
8.5.2. 
Pharmacokinetic Sample Analysis ............................................... 70 
8.6. 
Pharmacodynamics .................................................................................... 70 
8.7. 
Genetics ..................................................................................................... 70 
8.8. 
Biomarkers ................................................................................................. 70 
8.8.1. 
BCMA Sample Analysis ............................................................... 70 
8.8.2. 
Immunogenicity Assessments ...................................................... 71 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 72 


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9.1. 
Statistical Hypotheses................................................................................. 72 
9.2. 
Sample Size Determination ........................................................................ 72 
9.3. 
Populations for Analyses ............................................................................ 72 
9.4. 
Statistical Analyses ..................................................................................... 72 
9.4.1. 
Key Elements of Analysis Plan .................................................... 72 
9.4.2. 
Dose Limiting Toxicity .................................................................. 73 
9.4.3. 
Safety Analyses ........................................................................... 73 
9.4.4. 
Extent of Exposure ...................................................................... 73 
9.4.5. 
Adverse Events............................................................................ 73 
9.4.6. 
Clinical Laboratory Evaluations .................................................... 73 
9.4.7. 
Immunogenicity Analyses ............................................................ 73 
9.4.8. 
Other Safety Measures ................................................................ 74 
9.4.9. 
Clinical Activity Analyses ............................................................. 74 
9.4.10. 
Pharmacokinetic Analyses ........................................................... 74 
9.4.11. 
Pharmacokinetic/Pharmacodynamic Analyses ............................. 75 
9.4.12. 
Pharmacodynamic Biomarkers and Exploratory Response 
Prediction Biomarkers .................................................................. 75 
9.5. 
Interim Analyses ......................................................................................... 75 
9.5.1. 
Data Monitoring Committee (DMC) .............................................. 75 
9.5.2. 
Dose Escalation Committee (DEC) .............................................. 75 
10. REFERENCES ....................................................................................................... 77 
11. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 80 
11.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 80 
11.1.1. 
Regulatory and Ethical Considerations ........................................ 80 
11.1.2. 
Financial Disclosure ..................................................................... 80 
11.1.3. 
Informed Consent Process .......................................................... 81 
11.1.4. 
Data Protection ............................................................................ 81 
11.1.5. 
Dissemination of Clinical Study Data ........................................... 81 
11.1.6. 
Data Quality Assurance ............................................................... 82 
11.1.7. 
Source Documents ...................................................................... 83 
11.1.8. 
Study and Site Closure ................................................................ 83 
11.1.9. 
Publication Policy ......................................................................... 83 
11.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 84 
11.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 86 
11.3.1. 
Definition of AE ............................................................................ 86 
11.3.2. 
Definition of SAE .......................................................................... 87 
11.3.3. 
Definition of Cardiovascular Events ............................................. 88 
11.3.4. 
Recording and Follow-Up of AE and SAE .................................... 89 
11.3.5. 
Reporting of SAE to GSK ............................................................. 91 
11.4. 
Appendix 4: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................. 92 
11.5. 
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments and Study treatment Rechallenge Guidelines ....................... 95 
11.5.1. 
Liver Safety Drug Restart or Re-Challenge Guidelines ................ 97 
11.5.1.1. Re-challenge Following Liver Stopping Events 
that are Possibly Related to Study treatment .............. 98 


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11.5.1.2. Re-challenge Following Transient Liver 
Stopping Events Not Related to Study 
treatment .................................................................... 99 
11.5.2. 
References ................................................................................ 100 
11.6. 
Appendix 6: International Myeloma Working Group Uniform 
Response Criteria for Multiple Myeloma (2016) ........................................ 101 
11.7. 
Appendix 7: ECOG Performance Status1 ................................................. 104 
11.8. 
Appendix 8: Modified Diet in Renal Disease (MDRD) Formula .................. 105 
11.9. 
Appendix 9: Eye Care Specialist’s Qualifications and Requirements ........ 106 
11.10. Appendix 10: Abbreviations and Trademarks ............................................ 107 
11.11. Appendix 11: Protocol Amendment History ............................................... 111 
 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Phase I Open-label, Dose Escalation Study to Investigate the Safety, 
Tolerability, Pharmacokinetics, Immunogenicity and clinical activity of the Antibody 
Drug Conjugate belantamab mafodotin in Chinese Participants with Relapsed/Refractory 
Multiple Myeloma Who Have Failed At Least Two Lines of Previous Treatment, 
Containing an alkylator, a Proteasome Inhibitor and an Immunomodulatory Agent  
Short Title: Phase I dose escalation study of belantamab mafodotin in Chinese 
participants with relapsed/refractory multiple myeloma 
Rationale: 
This is the first study for belantamab mafodotin in China to assess the safety, tolerability, 
pharmacokinetics (PK), immunogenicity and clinical activity of belantamab mafodotin in 
Chinese participants with multiple myeloma (MM). Belantamab mafodotin is a humanised 
(IgG1) antibody-drug conjugate (ADC) that binds to B-cell maturation antigen (BCMA), 
a target widely expressed on malignant plasma cells in MM. The parent anti-BCMA 
antibody is conjugated to the microtubule inhibitor, monomethyl auristatin-F (MMAF), 
which is released inside the malignant cell after binding and internalisation 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 tumour necrosis factor (TNF) family 
(BAFF/BLyS), and a proliferation-inducing ligand (APRIL). Belantamab mafodotin 
induces immunogenic cell death (ICD) in a BCMA-expressing multiple myeloma cell line. 
Exposure of dendritic cells to tumour cells undergoing ICD induces an antigen-specific T 
cell response.  
Preliminary clinical data from the global ongoing BMA117159 study as of the data cut 
off of 31 Aug 2018, a total of 73 participants with RRMM have been treated with at least 
one dose of belantamab mafodotin. The Part 1 dose-escalation phase enrolled 38 
participants at doses ranging from 0.03 mg/kg IV up to 4.6 mg/kg IV. Belantamab 
mafodotin was well tolerated with no DLTs up to 4.6 mg/kg q3w; MTD was not reached. 
The Part 2 dose expansion phase has enrolled 35 participants with MM at the 
recommended Phase 2 dose (RP2D) of 3.4 mg/kg IV, Q3W and has demonstrated an 
objective response rate (ORR) of 60% [95% confidence interval (CI): 42.1%, 76.1%], in 
heavily pre-treated participants with relapsed/refractory multiple myeloma (RRMM). The 
median duration of response (DOR) was 14.3 months [95% CI: 10.6, NA]; the median 
progression free survival (PFS) in this population was 12.0 months [95% CI: 3.1, not 
evaluable [NE]. Overall, belantamab mafodotin has a manageable safety profile with 
thrombocytopenia/platelet count decreased and corneal events as the most commonly 
reported events. Based on these data, GSK has initiated Study 205678, a global phase II 
study evaluating the safety and efficacy of belantamab mafodotin monotherapy (3.4 and 
2.5 mg/kg administered once every 3 weeks) in participants with relapsed / refractory 
multiple myeloma previously treated with at least 3 classes of drugs, including PIs, 
IMIDs and an anti-CD38 antibody, and who have demonstrated disease progression on or 
within 60 days of completion of the last therapy. 


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Study 208465 is designed to evaluate the safety, tolerability, PK, immunogenicity and 
clinical activity of belantamab mafodotin in Chinese participants with RRMM who have 
received at least 2 prior line of anti-myeloma therapy including an alkylator, a 
proteasome inhibitor (PI) and an immunomodulatory agent (IMiD). 
Objectives and Endpoints: 
Objectives  
Endpoints 
Primary Objectives 
• 
To determine safety and tolerability 
of belantamab mafodotin in Chinese 
Participants with RRMM  
• 
Adverse events (AE), i.e., number (%) of 
participants with DLTs, number (%) of 
participants with AEs 
Secondary Objectives 
• 
To evaluate PK profile of 
belantamab mafodotin in Chinese 
Participants with RRMM 
• 
ADC, total antibody and cys-mcMMAF PK 
parameters following IV single and repeat dose 
administration during dose escalation as data 
permit (e.g., AUC, Cmax, tmax) 
• 
To evaluate safety and tolerability of 
belantamab mafodotin 
• 
Changes in clinical signs and laboratory 
parameters, ocular findings on ophthalmic 
exam 
• 
To evaluate the clinical measures of 
efficacy of belantamab mafodotin  
 
• 
ORR, defined as the percentage of participants 
with a confirmed partial response (PR) or 
better (i.e., VGPR, CR and stringent complete 
response [sCR]), according to the International 
Myeloma Working Group (IMWG) Response 
Criteria. 
• 
To assess anti-drug antibody (ADA) 
formation after IV single and repeat 
dose administration of 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 OSDI 
Abbreviations: IV = intravenous; BCMA = B-cell maturation antigen; MMAF = monomethyl auristatin-F; ORR = overall 
response rate; CR = complete response; VGPR = very good partial response; PR = partial response ; AUC = area 
under the curve; Cmax = maximum concentration; Tmax = time to maximum; FLC =  free light chain; SCT = stem cell 
transplant; OSDI = Ocular Surface Disease Index. 
 


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Overall Design: 
This is a Phase I, open-label study to explore safety, tolerability, PK, immunogenicity 
and clinical activity of belantamab mafodotin monotherapy in Chinese participants with 
RRMM. Projected dose levels are 2.5 mg/kg and 3.4 mg/kg. De-escalation to 1.9 mg/kg 
will be allowed in case of ≥2 DLT at dose 2.5 mg/kg. The sample size planned is based 
on predefined dose escalation criteria for dose selection and is not driven by statistical 
considerations.  
As per current available safety and efficacy information of belantamab mafodotin studies, 
the 3.4 mg/kg dose cohort is converted to an optional cohort in the dose-escalation study 
design. Escalation may not proceed if not supported by emerging clinical data from other 
belantamab mafodotin studies. 
Based on the 3+3 dose escalation design the anticipated size will be up to 6 evaluable 
participants for each dose level.  
Belantamab mafodotin will be administered via 30-60 min intravenous (IV) infusion once 
every three weeks (21 days = 1 cycle). Extensive PK sampling will be collected at first 
cycle to characterize belantamab mafodotin exposures for each dose level.  
Disclosure Statement: 
This is an open-label, single arm, no masking study. 
Number of Participants: No formal statistical hypotheses are being tested. Analysis of 
the data obtained will only utilise descriptive methods. The sample size planned arises 
from the predefined dose escalation criteria for dose selection and is not driven by 
statistical considerations. Based on the 3+3 dose escalation design the anticipated size 
will be up to 6 evaluable participants for each dose level. The dose escalation decisions 
will be based on the recommendation from the Dose Escalation Meeting as well as the 
totality of the safety, tolerability and pharmacokinetics. 
Intervention Groups and Duration: 
Belantamab mafodotin will be administered via 30-60 min intravenous (IV) infusion once 
every three weeks on day 1. Participants will be treated until disease progression, 
intolerable toxicity, end of study or informed consent withdrawal. 
Treatment Arms 
Dose escalation will characterize the safety, tolerability and immunogenicity of 
escalating doses of belantamab mafodotin. The following dose levels of belantamab 
mafodotin are planned to be studied: 2.5 mg/kg and 3.4 mg/kg. 
Data Monitoring Committee: No 
Dose Escalation Meeting: Yes 
Inclusion Criteria 


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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 
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. Histological or cytologically confirmed diagnosis of MM as defined according to 
IMWG, 2014 criteria and  
a. Has undergone autologous stem cell transplant or transplant is considered 
not feasible by local assessment. 
b. Has failed at least 2 prior lines of anti-myeloma treatments, containing 
ALL of the following classes of drugs: alkylating agent, IMID and PI.  
c. In addition, eligible participants needs to be refractory to an IMiD (i.e., 
lenalidomide or pomalidomide), and to a proteasome inhibitor (i.e., 
bortezomib, ixazomib or carfizomib) as defined by IMWG criteria.  
d. Participants who failed with CD38 antibody (i.e., daratumumab) in 
previous clinical trials can also be considered to include if they meet the 
remainder of inclusion criteria in this protocol. 
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 functions 


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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 
eGFR1 
Spot urine (albumin/creatinine ratios (spot urine) 
30 mL/min/ 1.73 m1  
<500 mg/g (56 mg/mmoL) 
Cardiac 
LVEF (Echo) 
25%2 
1. 
As calculated MDRD equation 
2. 
It is acceptable to use an existing ECHO result, if performed within three months of screening. For participants 
with abnormal LVEF (per institutional standards), the participant is to follow-up with a cardiologist. For 
participants with low LVEF (per institutional standards), consider referring to cardiology per local standards of 
care. 
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 4 months after the last dose of study treatment 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 treatment. 
 
A WOCBP must have a negative highly sensitive serum pregnancy test within 
72 hours of dosing on C1D1 and agree to use effective contraception during the 
study and for 4 months after the last dose of study treatment.  
 
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 from the 
time of first dose of study until 6 months after the last dose of study treatment to 
allow for clearance of any altered sperm:  
• Refrain from donating sperm 
PLUS either: 
• Be abstinent from heterosexual intercourse as their preferred and usual 
lifestyle (abstinent on a long term and persistent basis) and agree to remain 
abstinent.  
OR 
• Must agree to use contraception/barrier as detailed below: 
Agree to use a male condom, even if they have undergone a successful 
vasectomy and female partner to use an additional highly effective 
contraceptive method with a failure rate of <1% per year 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 5.0 must 
be ≤Grade 1 at the time of enrolment except for alopecia and Grade 2 peripheral 
neuropathy. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Systemic anti-myeloma therapy within <14 days, or plasmapheresis within 7 days 
prior to the first dose of study drug 
2. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, 
organomegaly, endocrinopathy, myeloma protein, and skin changes), active 
plasma cell leukemia at the time of screening. 
3. Prior allogeneic stem cell transplant (SCT)  
4. Current corneal epithelial disease except mild punctate keratopathy. 
5. 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.  
6. Evidence of active mucosal or internal bleeding 
7. Any major surgery within the last four weeks 


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8. 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. 
9. 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.  
10. 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. 
11. 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.  
12. Evidence of cardiovascular risk including any of the following: 
a. QTcF interval >480 msecs (the QT interval values must be corrected for 
heart rate by Fridericia’s formula [QTcF]) 
b. Evidence of current clinically significant untreated arrhythmias, including 
clinically significant ECG abnormalities such as 2nd degree (Mobitz 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 three months of Screening. 
d. Class III or IV heart failure as defined by the New York Heart Association 
functional classification system 
e. Uncontrolled severe hypertension, e.g. 170/110 
13. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs 
chemically related to belantamab mafodotin, or any of the components of the 
study drug. 
14. Pregnant or lactating female. 
15. Active infection requiring antibiotic, antiviral, or antifungal treatment. 
16. Known HIV infection. 


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17. 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) 
18. 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. 
Schema 
Figure 1 
Study Design 
 
Note: De-escalation to 1.9 mg/kg will be allowed in case of ≥2 DLT at dose 2.5 mg/kg 
As per current available safety and efficacy information of belantamab mafodotin studies, the 3.4 mg/kg dose cohort 
is converted to an optional cohort in the dose-escalation study design. Escalation may not proceed if not supported 
by emerging clinical data from other belantamab mafodotin studies. 
 


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1.3. 
Schedule of Activities (SoA) 
Table 1 
Schedule of Activities for belantamab mafodotin Study 208465 - Every 3 Weeks Dosing Schedule for RRMM 
Study Assessments 
Screen1 
Cycle 1 
Day 12 
Cycle 1 
Day 2 
Cycle 1 
Day 4 
Cycle 1 
Day 8 
Cycle 1 
Day 15 
Treatment Period3 Cycle = 21 days 
End of 
Treatment 
Follow-up4 
PD Follow-up5 
D1 of C2 - CX 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Baseline 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical History 
including disease 
history and 
characteristics 
X 
 
 
 
 
 
 
 
 
Physical Exam 
X 
X 
 
 
 
 
X every 3 weeks 
X 
X 
Safety 
 
Ocular Exam 
X6 
 
 
 
 
 
X7 
X7 
X8 
ECOG Performance 
Status 
X 
 
 
 
 
 
X every 3 weeks 
X 
 
Vital Signs (BP, HR, 
Body Temperature) 9, 
10 
X 
X 
 
 
X 
X 
X 
X 
 
Weight9 and Height 
X 
Weight 
only 
 
 
 
 
Weight only 
Weight only 
 
Hematology11 
X 
X 
 
X 
X 
X 
X every 3 weeks 
X 
 
Clinical chemistry11 
X 
X 
X 
X 
X 
X 
X every 3 weeks 
X 
X11 
Urine Dipstick11 
X 
X 
 
 
 
 
X every 3 weeks 
X 
X 
eGFR (by MDRD 
formula- see Appendix 
8) 
X 
X 
 
 
 
 
X every 3 weeks 
X 
 
Spot urine for 
creatinine/albumin 
ratio12 
X 
X 
 
 
 
 
Cycle: 3, 5, 7 and Every other cycle 
thereafter 
X 
 
CRP 
X 
 
 
 
 
 
X every 3 weeks 
X 
 


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Study Assessments 
Screen1 
Cycle 1 
Day 12 
Cycle 1 
Day 2 
Cycle 1 
Day 4 
Cycle 1 
Day 8 
Cycle 1 
Day 15 
Treatment Period3 Cycle = 21 days 
End of 
Treatment 
Follow-up4 
PD Follow-up5 
D1 of C2 - CX 
HBsAg, HBcAb, and 
hepatitis C Ab.13 
X 
 
 
 
 
 
 
 
 
Troponin I14 
X 
 
 
 
 
 
 
 
 
BNP15 
X 
 
 
 
 
 
 
 
 
Pregnancy Test 9, 16 
X 
X 
 
 
 
 
X 
X 
X16 
ECHO17 
X 
 
 
 
 
 
as clinically indicated 
 
 
12-lead ECG9, 18 
X 
X18 
X18 
X18 
X18 
X18 
X. 
X 
 
PK and ADA 
 
PK19 
 
X19 
X19 
X19 
X19 
X19 
X19 
X20 
 
ADA21 
 
X21 
 
 
 
 
X21 
X21 
 
Disease Evaluation 
 
2 Microglobulin 
X 
 
 
 
 
 
 
 
 
Response 
assessment22 
 
 
 
 
 
 
X every 3 weeks 
X23 
X 
 Skeletal survey24 
X 
 
 
 
 
 
As clinically indicated 25 
 
 
Imaging for 
Extramedullary 
disease26 
X 
 
 
 
 
 
C5, C9, C13 and C17, every12 
weeks then as clinically indicated 26 
X 27 
X 
UPEP (Urine Protein 
Electrophoresis) 24 hr 
urine collection 
X 
 
 
 
 
 
X every 3 weeks 
X 
X 
Urine Immunofixation 
X 
 
 
 
 
 
At time of first achieving CR or 
suspected PD after CR or sCR 
At time of first 
achieving CR or 
suspected PD 
after CR or sCR 
At time of first 
achieving CR or 
suspected PD after 
CR or sCR 
SPEP (Serum Protein 
Electrophoresis) 
X 
 
 
 
 
 
X every 3 weeks 
X 
X 


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Study Assessments 
Screen1 
Cycle 1 
Day 12 
Cycle 1 
Day 2 
Cycle 1 
Day 4 
Cycle 1 
Day 8 
Cycle 1 
Day 15 
Treatment Period3 Cycle = 21 days 
End of 
Treatment 
Follow-up4 
PD Follow-up5 
D1 of C2 - CX 
Serum immunofixation 
X 
 
 
 
 
 
At time of CR or suspected PD after 
CR or sCR 
At time of CR or 
suspected PD 
after CR or sCR 
At time of CR or 
suspected PD after 
CR or sCR 
Serum Kappa, lambda 
free LC, FLC ratio 
X 
 
 
 
 
 
X every 3 weeks 
X 
X 
Calcium corrected for 
albumin (serum) 
X 
 
 
 
 
 
X every 3 weeks 
X 
X 
IgG, IgM, IgA 
X 
X 
 
 
 
 
X every 3 weeks 
X 
X  
IgD/E28 
X 
X 
 
 
 
 
X every 3 weeks 
X 
X 
Bone Marrow Aspiration / biopsy 
FISH testing on bone 
marrow29 
X 
 
 
 
 
 
 
 
 
BM for disease 
assessment31 
X 
 
 
 
 
 
At the time of CR (always) or at time 
of suspected PD (only if not evident 
otherwise) 
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 
Bone marrow to 
assess sCR by (IHC)32 
 
 
 
 
 
 
X32 
Only if CR has 
been achieved 
on this visit. 
Only if CR have 
been achieved on 
this visit 
Biomarker 
 
Study treatment 
 
Premedication if 
needed 
 
X 
 
 
 
 
X 
 
 
Belantamab mafodotin 
administration34 
 
X 
 
 
 
 
X 
 
 
Preservative-free 
artificial tears35 
 
X 
 
 
 
 
Everyday until end of Study 
treatment 
 
 
Adverse Events36 
 
X 
X 
X 
X 
X 
X 
 
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Study Assessments 
Screen1 
Cycle 1 
Day 12 
Cycle 1 
Day 2 
Cycle 1 
Day 4 
Cycle 1 
Day 8 
Cycle 1 
Day 15 
Treatment Period3 Cycle = 21 days 
End of 
Treatment 
Follow-up4 
PD Follow-up5 
D1 of C2 - CX 
Concomitant 
Medications 
X 
X 
X 
 
X 
X 
X 
 
Health Outcomes 
OSDI37 
X 
X 
 
 
 
 
X  every 3 weeks 
X 
X 
Abbreviations: 
ADA = Anti-drug Antibody; ALP = alkaline phosphatase; BM = bone marrow; BNP = B-type natriuretic peptide; BP = blood pressure; C1D1 = Cycle 1 Day 1, etc.;  CK = creatine kinase;  
CRP = C-reactive protein; EM = extramedullary;  EOI = End of Infusion; FISH = fluorescence in situ hybridization; FLC = free light chain; HR= heart rate; Ig = immunoglobulin;  PK = 
Pharmacokinetics; QID = 4 times a day; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis; OSDI = Ocular Surface Disease Index 
 
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 C1D1 unless otherwise specified. 
2. 
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. 
3. 
Belantamab mafodotin will be administered intravenously on Day 1 (D1) of every 21-day cycle until disease progression, death, unacceptable toxicity, withdrawal of consent 
or end of study. 
4. 
The End of treatment (EOT) follow-up visit is to assess any residual AEs or toxicities associated with Study treatment. The visit should occur -within 45 days after last dose or 
before the start any new anti-cancer therapy.  
5. 
PD follow-up once every 21 days: Participants who discontinue IP for a reason other than PD, disease evaluations will continue to be performed once every 21 days (±7 
days) until confirmed PD, death, start of a new anticancer treatment, withdrawal of consent, or end of the study whichever occurs first.  
6. 
Screening examination will be performed by an ophthalmologist (or an optometrist if an ophthalmologist is not available) within 21 days prior to first dose. See Section 8.3.9 
for the list of ophthalmic exam procedures. 
7. 
On-study ophthalmic exams to be performed by an ophthalmologist (or an optometrist if an ophthalmologist is not available) pre-dose every 3 weeks (schedule of assessment 
window should be within 5 days prior to dosing, all efforts should be made to schedule as close to dosing as possible). After the 6th dose of belantamab mafodotin (no 
schedule of assessment window needed): If there are no significant (Grade 2 or above) ocular symptoms or vision changes the frequency of ophthalmologic exams may be 
decreased to every 3 months until end of treatment. In case of persistent ocular exam findings, newly developed ocular symptoms or vision changes, further ocular exams 
should be performed at least every cycle until resolution (to Grade 1 or baseline) or more frequently as clinically indicated by the qualified eye care specialist (Appendix 9). 
See Section 8.3.9 for the list of ophthalmic exam procedures  
8. 
Additional exams may be performed by the ophthalmologist (an optometrist if an ophthalmologist is not available), as clinically indicated.  
9. 
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:  
ECG, weight, vitals, pregnancy test. Please follow the visit schedule in the SOA above, and perform these activities prior to a belantamab mafodotin infusion 
10. 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, end of infusion (EOI), 
and 1 hour post EOI. On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), and at EOI. On days where vital sign time points 
align with PK sampling time points, vital signs must 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.  


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11. Refer to Table 9 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 Day 1 of Cycle 1. Creatinine only is required at PD visits (not a full chemistry).  
12. Creatinine / albumin ratios (spot urine from first void) at screening and C1, C3, C5, C7 and every other cycle thereafter (local labs or central if local not available). 
13. 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 negative- 
participant is eligible).  
14. 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 must 
be measured.  
15. 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 must be measured. 
16. Perform only in women of childbearing 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, follicle stimulating hormone (FSH) and estradiol (as needed in women of non-child bearing potential only) should be performed at local lab. See 
Section 5.1, Section 8.3.5, and Appendix 4 for more details. 
a. 
Final pregnancy test (serum or urine) must be performed in women of childbearing potential at the EOT Visit, and 8 months after the last dose of study 
treatment may be via a urine pregnancy test kit mailed to the participant’s home with results reported by telephone.  
17. Echocardiography for LVEF performed within 3 months of screening are acceptable as screening value. For participants with an abnormal LVEF (per institutional standards), 
the participant is to follow-up with a cardiologist. 
18. ECGs on dosing days: Triplicate ECGs to be performed at pre-dose (within 30 minutes prior to SOI) and EOI at cycle 1. Triplicate ECGs should be collected prior to PK 
sample on Cycle 1 Day 2, Day 4, Day 8 and Cycle 1 Day 15. Single ECG at screening, at all other cycles, and End of Study Treatment. On days where ECG time points align 
with PK sampling time points, ECGs must be performed within 30 minutes prior to PK samples being drawn (PK sample must be taken at the exact nominal time). ECGs will 
be collected and stored at site. See SRM for details on collection regarding ECGs. 
19. PK samples to be taken in all participants for belantamab mafodotin ADC, total antibody and cys-mcMMAF measurements on: 
- C1D1 at pre-dose (within 30 minutes prior to SOI), at the end of infusion (EOI) (+5 min), 2 h post-SOI (±15 min), 4 h post-SOI (±15 min), 8 h post-SOI (±1 h), 24 h post-SOI 
(±2 h); 
- C1D4 anytime (±1 day);  
- C1D8 anytime (±1 day);  
- C1D15 anytime (±1 day);   
- C1D22 anytime (±1 day) (collect one PK sample only if the dose for the next cycle is delayed; this sample will combined) 
- For C2D1, C4D1, C6D1, C9D1, and C12D1, collect samples at pre-dose (within 30 min prior to SOI) and at the EOI (+5 min);  
- For every six cycles after C12 (e.g., C18, C24, etc.), collect one sample at pre-dose (within 30 min prior to SOI). However, one year after the first dose of last subject, PK 
samples will only be collected for the interpretation of ADA results in the following visits.  
20. Collect 1 PK sample at each participant’s final visit.  
21. All ADA samples will be collected prior to each infusion at C1, C2, C4, C6, C9, C12, and every 6 cycles thereafter (C18, C24, etc.) until end of treatment (dosing days only) 
and at the last visit. 
22. Disease Response Assessment:  Response assessment must be conducted Q3W based on standard disease laboratory tests (serum and urine M protein test, FLC, IgD/E, if 
applicable), Ca corrected for albumin, bone marrow aspirate (in case of CR, or suspected PD if not evident otherwise). Assessment based on imaging has to be included in 


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participants with extramedullary disease at indicated time points. Response evaluation will be performed according to the IMWG Uniform Response Criteria for Multiple 
Myeloma 2016.  
23. For participants who are discontinuing IP due to PD the confirmation must performed on a different date from a different blood collection within 14 days of the original disease 
progression. This may be performed at the at EOT follow-up visit.  
24. Skeletal Survey: Imaging of bones for lytic lesions by a method aligned with the institutional guidance (X-ray, CT [Computed tomography], or MRI [Magnetic resonance 
imaging]). Skeletal survey results within 30 days prior to C1D1 are acceptable.  
25. Only if clinically indicated or if worsening clinical symptoms suggest PD.  
26. Imaging is only required for participants with extramedullary disease (CT, MRI, or PET [Positron Emission Tomography ]/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 (i.e., if PET scan was used as baseline, participant 
needs to be followed by PET 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). Evaluations should be performed by the same method as at screening.  
27. In participants with extramedullary MM, if the last radiographic assessment occurred ≥8 weeks prior to the participant’s withdrawal from study treatment, and progressive 
disease has NOT been documented –then a new assessment (presence or absence extramedullary disease) should be obtained at the time the participants withdrew from 
study treatment. 
28. Only required for participants with IgD/E myeloma, where serum m-component cannot be followed otherwise 
29. FISH testing at least for: t (4;14), t (14;16), 17p13del, and +1q21. FISH results from samples taken within 60 days prior to first dose are acceptable. If this cannot be 
performed at a local lab the samples can be sent to the central lab 
30.
31. Bone Marrow for disease assessment performed within 14 days prior to first dose is acceptable.  
32. Bone marrow biopsy for IHC to confirm sCR after achieving a CR. 
33.
34. Belantamab mafodotin administration: Study drug administration r3-day window.  
35. 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. 
36. All related SAEs are to be collected from consent through PD follow-up. 
37. Additional assessments may be conducted for those participants who experience a worsening in visual function.  Participants who discontinue participation in the study will 
continue to be assessed during follow-up until resolution of visual symptoms.  Continue to follow up with participants via telephone who are still experiencing visual symptoms 
even after discontinuation. 

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2. 
INTRODUCTION 
2.1. 
Study Rationale 
Multiple myeloma (MM) is a neoplastic plasma cell disorder that is characterized by 
osteolytic bone lesions, anaemia, hypercalcaemia and renal failure [Palumbo, 2011; 
Rajkumar, 2011a]. Worldwide, approximately 103,000 new MM cases and 80,000 deaths 
are diagnosed annually, MM accounts for 1% of all cancer and 10% of hematologic 
malignancies [Ferlay, 2010; Siegel, 2016]. Multiple myeloma is slightly more common in 
African-americans and Caucasians relative to Asians, the incidence rate is increasing in 
some Asian countries [Rajkumar, 2011b; Kim, 2014]. Based on GLOBOCAN report an 
estimated 20,066 new cases and 14,655 deaths will occur in China in 2018 
[GLOBOCAN, 2018]. 
A variety of drugs and combination treatments have been evaluated and found effective 
in treating MM [NCCN, 2016; Moreau, 2017]. However, most, if not all, of these 
participants inevitably relapse [Richardson, 2003; Richardson, 2006; Jagannath, 2008]. 
Belantamab mafodotin is a humanised (IgG1) antibody-drug conjugate (ADC) which 
binds to B-cell maturation antigen(BCMA), a target widely expressed on malignant 
plasma cells in MM. The parent anti-BCMA antibody is conjugated to the microtubule 
inhibitor, Monomethyl auristatin-F (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 tumour necrosis factor (TNF) family (BAFF/BLyS), and a 
proliferation-inducing ligand (APRIL). Belantamab mafodotin induces immunogenic cell 
death (ICD) in a BCMA-expressing multiple myeloma cell line and leads to dendritic cell 
activation/maturation. Exposure of dendritic cells to tumour cells undergoing ICD 
induces an antigen-specific T cell response.  
Study 208465 is designed to evaluate the safety, PK, immunogenicity and clinical activity 
of belantamab mafodotin in Chinese participants with RRMM who have received at least 
2 prior lines of anti-myeloma therapy including an alkylator, a proteasome inhibitor (PI) 
and an immunomodulatory agent (IMiD).  
2.2. 
Background 
Immunomodulatory drugs e.g. lenalidomide, thalidomide, pomalidomide) and 
proteasome inhibitors (PIs e.g. bortezomib, carfilzomib, ixazomib) are still the main 
pillars of MM treatment, and have been used in combination, often with dexamethasone, 
to deliver better efficacy [NCCN, 2016]. These highly active agents used in combination 
are providing tangible benefits for participants with MM [Rajkumar, 2011b]. Importantly, 
improvements in survival outcomes have been noted in participants with MM and current 
treatment strategies provide a very good chance for response in the first line. 
Unfortunately, duration of response and response rates decline dramatically in each 
subsequent line of treatment for this malignancy. Relapsed/ refractory multiple myeloma 
(RRMM) remains incurable and the need for new treatment modalities is well recognised.  
Three and four-drug combinations are now emerging for participants with RRMM. For 
example, a monoclonal antibody (mAb) such as daratumumab (targeting CD38) and 


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elotuzumab (targeting signalling lymphocyte activation molecule [SLAMF7]) represent 
treatments with novel mechanisms of action that are now used in combination with other 
standard regimens that include immunomodulatory imide drugs, proteasome inhibitors 
(PIs), and corticosteroids [Lonial, 2014; Lokhorst, 2015; NCCN, 2016]. Despite those 
new combinations, relapse rates remain high and high toxic effects may limit their 
application [NCCN, 2016].  
In China, bortezomib and lenalidomide have been currently approved for 1st line use 
while daratumumab and pomalidomide  have been newly approved as  2nd line plus MM 
treatment.  RRMM participants double refractory to bortezomib and lenalidomide 
currently still have limited treatment options available while other new agents are under 
development in China. The China Center for Drug Evaluation, National Medical Products 
Administration (CDE, NMPA) has recommended Breakthrough Therapy Designation 
(BTD) for ciltacabtagene autoleucel. A B-cell maturation antigen (BCMA) targeted 
chimeric antigen receptor (CAR) T-cell therapy is under development for the treatment of 
adults with RRMM. Currently, a Phase 1 and Phase 2 studies are ongoing in China with 
ciltacabtagene autoleucel. Therefore, a high unmet medical need for MM exists in China. 
Belantamab mafodotin is a first in class, afucosylated, humanised 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 tumour cells of all participants with MM [Tai, 2015; Tai, 2006]. The 
antibody 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 internalised 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-tumour 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 tumour cells undergoing ICD induces an antigen-
specific T-cell response, and if it acts similarly in humans could induce the participant’s 
own immune response against the MM tumour.  
BLENREP (belantamab mafodotin) monotherapy, for the treatment of adult patients with 
relapsed/refractory multiple myeloma is the first anti-BCMA (B-cell maturation antigen) 
therapy approved in the US and in the European Union. The efficacy and safety results 
from study BMA117159/DREAMM-1 and study 205678/DREAMM-2 indicate that 
belantamab mafodotin is an effective single-agent treatment option for patients with 
RRMM, with a novel MOA. In binding to BCMA on malignant plasma cells, belantamab 
mafodotin initiates cell killing via a multimodal-mechanism, including delivering MMAF 
to BCMA-expressing MM cells, inducing apoptosis, enhancing antibody-dependent 


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cellular cytotoxicity and antibody-dependent cellular phagocytosis, and inducing 
immunogenic cell death. 
2.3. 
Human Experience with Belantamab Mafodotin 
2.3.1. 
Clinical studies 
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 Sep 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 [GlaxoSmithKline Document Number RPS-CLIN-004867; 
Trudel, 2019].  
As of the efficacy cut-off date of 31 Aug 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 
evaluable [NE]). For participants refractory to both immunomodulatory imide drugs and 
PIs (n = 32/35), the confirmed ORR was 56% (95% CI: 37.7, 73.6) and mPFS was 7.9 
months (95% CI: 2.3, NE) [Trudel, 2019].  
Phase II study 205678/DREAMM-2 
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 imide drug 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 Jan 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 


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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)].  
2.3.2. 
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 Sep 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 favourable 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. 
Adverse Events of Special Interest 
Thrombocytopenia 
In DREAMM-2 (data as of 31 Jan 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. 
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 as of 31 Jan 2020), events in the Eye disorders SOC occurred in 
78% of participants treated with belantamab mafodotin 2.5 mg/kg. The most common 


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Details of the characteristics of belantamab mafodotin, nonclinical, and clinical activity 
are provided in the Investigator’s Brochure (IB) [Belantamab mafodotin 
GlaxoSmithKline Document Number RPS-CLIN-004867, 2021]. 
This is the first study for belantamab mafodotin in China to assess the safety, tolerability, 
pharmacokinetics (PK), immunogenicity and clinical activity of belantamab mafodotin in 
Chinese participants with MM. 
2.4. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and 
reasonably expected adverse events of belantamab mafodotin may be found in the IB 
[Belantamab mafodotin GlaxoSmithKline Document Number RPS-CLIN-004867]. 


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2.4.1. 
Risk Assessment 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Investigational Product (IP) [Belantamab Mafodotin] 
Changes on Corneal Examination 
Changes in corneal epithelium on ocular examination have 
been frequently observed with belantamab mafodotin such as 
superficial punctate keratopathy, microcyst-like changes, sub-
epithelial haze, corneal erosions and corneal ulcers. These 
were most commonly associated with: blurred vision, dry eyes, 
photophobia, and changes in visual acuity. 
 
Participants with a history of dry eye were more prone to 
develop changes in the corneal epithelium. 
 
Based on available follow-up data, visual acuity returned to, or 
near baseline in most cases and no permanent loss of vision 
reported. 
 
Corneal ulcers or erosions are distinguished by the presence or 
absence of stromal involvement, respectively. The precise 
incidence has yet to be defined. The corneal defects (with or 
without stromal involvement) appeared as early as the second 
or third cycle but in most cases after 5 or more cycles of 
treatment 
Active monitoring for corneal events according to the SoA 
(Table 1).  
 
In the event of new-onset eye-related symptoms (such as 
pain, significant loss of visual acuity, or bothersome 
foreign body sensation), participants are to urgently seek 
medical attention by a qualified eye care specialist 
(appropriate testing includes slit lap examination [includes 
fluorescein staining] and measurement of visual acuity). 
Appropriate management should be initiated immediately 
as defined in Section 6.6.1. 
 
Recommendations for dose delays/reductions and 
treatment stopping guidance are provided in Table 7 and 
Section 7.1. 
Infusion related reaction (IRR) 
IRRs were reported in participants treated with belantamab 
mafodotin. Most IRRs observed to date were Grade 1 to 2 and 
manageable with medical treatment. 
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 IRR occurs during belantamab mafodotin 
administration, management will follow guidance in 
Section 6.6 and Section 7.1.4 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Thrombocytopenia 
Thrombocytopenic events of all grades (1-4) are among the 
most common AEs associated with belantamab mafodotin.  
Belantamab mafodotin may cause transient thrombocytopenia 
in some participants, which for most cases recovered between 
doses. 
In the pooled safety population of study 205678 which included 
participants treated with belantamab mafodotin 2.5 and 
3.4 mg/kg, thrombocytopenia was noted in 46% of participants 
and ranged between Grade 1 to 4 in severity. 
Hematologic panels are monitored closely as outlined in 
Section 1.3. 
 
Supportive therapy (including transfusions) is provided 
according to standard medical practice, and dose 
reductions or treatment discontinuations are outlined in 
Section 6.6 and Section 7.1. 
 
 
Other hematological effects 
Neutropenic events, including febrile neutropenia have been 
observed with treatment with belantamab mafodotin. 
 
In a study of belantamab mafodotin in combination with 
lenalidomide/ dexamethasone, two fatal cases of severe 
infections associated with neutropenia were observed. 
 
Anemia is a common complication in the RRMM population and 
was frequently reported in the belantamab mafodotin clinical 
program. 
Hematologic panels are monitored closely as outlined in 
Section 1.3. 
 
Consider prophylactic antibiotics, per physician discretion 
and local institutional guidance, in participants with Grade 
3-4 neutropenia (ANC <1.0x109/L), even if afebrile. 
 
Immediately hospitalize participants with febrile 
neutropenia and initiate appropriate management, per 
local institutional guidance. 
 
Consider additional supportive treatment(s) per local 
practice (e.g., growth factors). 
 
 Dose reductions or treatment discontinuations are 
outlined in Section 6.6 and Section 7.1. 
Potential for cardiotoxicity related to an 
inflammatory response 
Nonclinical studies, predominantly in monkey, increased 
activation of macrophages was noted in a number of organs at 
≥3 mg/kg/week, reflective of a systemic inflammatory response. 
Minimal inflammatory changes (inflammatory cell infiltrate 
and/or haemorrhage) were also noted in hearts (atrial 
epicardium, ventricle endocardium) of single monkeys, which 
were nonadverse and reversible. 
Participants with significant cardiac risk factors will be 
excluded from study participation.  
 
Electrocardiograms will be monitored as per Section 1.3. 
 
Treatment as medically indicated.  
 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
No cardiac events were reported to date in MM participants 
receiving belantamab mafodotin in clinical trials.  
Monitoring of other cardiac parameters as clinically 
indicated. 
Hepatotoxicity 
In nonclinical studies liver is a target organ for toxicity, with 
increased liver weights and/or raised hepatobiliary enzymes 
and transaminases observed I both rat and monkey. These 
changes in the liver were without clinical consequence in the 
shorter duration studies and in the rat 13-week study. In the 
monkey 13-week study, progression of liver toxicity to include 
minimal multifocal hepatocellular necrosis was observed at all 
doses administered (≥3 mg/kg/week). 
Mild elevations of liver enzymes have been reported in some 
participants treated with belantamab mafodotin. 
Only participants with well-preserved liver function per the 
inclusion/exclusion criteria will be allowed on study.  
 
Participants with chronic Hepatitis B (HBV) and C will be 
excluded.  
 
Liver function tests will be regularly monitored (Section 
1.3). In case of liver abnormalities management will be 
implemented according to clinical practice.  
 
Participants that meet liver stopping criteria 
(Section 7.1.1) will be withdrawn from the study. 
Nephrotoxicity 
Non-clinical safety studies have demonstrated dose dependent 
and reversible primary glomerular injury and tubular 
degeneration (in rat and monkey), accompanied by large 
molecular proteinuria (albuminuria) and enzymuria. Single cell 
necrosis of the kidney and bladder urothelium was also noted in 
the 13-week monkey study. Severe tubular 
degeneration/regeneration and marked glomerulonephritis 
exacerbated by immune complex disease, likely associated with 
ADA, led to the early euthanasia of one monkey following 5 
weekly doses of 10 mg/kg.  
Increased albumin/creatinine ratio (albuminuria) not indicative of 
disease progression has been reported in clinical trials and 
named patient programs with belantamab mafodotin 
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 Study treatment stopping criteria will 
be applied according to Section  6.6  and Section 7.1 
Pulmonary toxicity (pneumonitis) 
Nonclinical safety experiments have demonstrated the 
presence of microscopic changes in the lungs (prominent 
alveolar macrophages associated with eosinophilic material; 
mixed perivascular inflammation) in rats at all doses tested.  
Monitoring for clinical signs and symptoms potentially 
related to pulmonary toxicity. If a participant experiences 
new or worsening pulmonary symptoms, (e.g., cough, 
dyspnea) without obvious etiology, appropriate diagnostic 
evaluation should be performed (see protocol Section 5.2) 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Cases of pneumonitis, including fatal events, have been 
observed with belantamab mafodotin although a causal 
association has not been established. 
To date, no significant pulmonary toxicity has been reported in 
studies BMA117159 or 205678. 
and further treatment with belantamab mafodotin delayed 
(refer to protocol Section 6.6). 
 
An overall benefit/risk assessment should be considered 
for the participant prior to continuing belantamab 
mafodotin treatment 
 
Further diagnostic tests and management will be 
implemented immediately according to recommendations 
provided in Section 6.6. 
Immunosuppression 
In nonclinical studies belantamab mafodotin has been 
associated with decrease in immunoglobulins in monkeys at all 
doses. An increase in immunoglobulins was seen in rats (rats 
are not an antigen specific species for belantamab mafodotin). 
Immunosuppression is frequently associated with an increased 
risk of infection. Serious and non-serious infections have been 
reported in belantamab mafodotin studies, including respiratory 
infections, pneumonia and sepsis. 
Participants who have active infection will be excluded. 
 
Participants will be monitored for infections and those 
who develop infection will receive immediate treatment 
according to standard practice. 
Potential for Other Laboratory abnormalities 
An increased magnitude of AST relative to ALT consistent with 
increased skeletal troponin I was observed in the single dose 
monkey study. Increased skeletal troponin I and/or creatine 
kinase and aldolase was observed in the rat 3-week study. 
Cases of elevated aspartate aminotransferase (AST), lactic 
dehydrogenase (LDH) and creatine kinase (CK), and GGT 
alone or concomitant with no clear clinical correlate have been 
observed in clinical studies. 
Laboratory parameters will be monitored as outlined in 
the SoA (Section 1.3). 
Participants with significant laboratory elevations (≥x3 
ULN) should, where possible, have a sample tested for 
CK and LDH isoenzyme levels. 
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]). 
See Contraception requirements in Section 5.1 and 
Appendix 4. 
Pregnancy testing outlined in the SoA. 1.3 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Use of belantamab mafodotin in pregnant women may cause 
fetal harm. 
Impaired Male and Female 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.  
Ovarian toxicity (luteinized non-ovulatory follicles) was observed 
in a 3-week rat study (weekly dosing) and not observed 
following 12 weeks off dose. In a 13-week rat study where drug 
was administered once every 3 weeks, these changes were not 
observed. 
Men who may wish to father children in the future will be 
advised to have sperm samples frozen and stored prior to 
belantamab mafodotin treatment.  
Women of child bearing potential who may desire 
offspring in the future will be counselled about the option 
of having eggs frozen before treatment. See 
Contraception requirements in Section 5.1 and Appendix 
4. 
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 data 
acquisition: 
During the acquisition of imaging data (e.g MRI, CT, PET, ECG 
), non- disease or 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 
Participants exposed to ionizing radiation  
The ionizing radiation exposure arises due to the inclusion in 
the study of imaging scans. Participation in this study will 
involve various imaging procedures based on the needs of the 
participant, some of which are standard of care and some are 
additional requirements for the study. The risk arising from the 
additional radiation burden is considered justified by the benefit 
of the clinical information to be obtained, which is critical to the 
study and cannot readily be obtained another way. All 
participants will have skeletal survey imaging at screening, and 
depending on clinical condition, some participants may also 
require additional imaging exams at regular intervals. Some of 
these procedures use ionizing radiation to form images of your 
body. The imaging procedures and doses that may be used for 
The study has been designed to keep the radiation dose 
as low as reasonably practicable whilst obtaining images 
of sufficient quality to meet the objectives. 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
this study could include X-Ray skeletal survey (~2 mSv), CT 
(10-20 mSv), FDG PET/CT (14 mSv) and/or MRI (no radiation 
exposure). For comparison, the average global yearly 
background radiation dose is 2.4 mSv. 
TCR = T-cell receptor; mAb = Monoclonal antibody; AEs = Adverse Events, MRI = Magnetic resonance imaging; CT = Computed tomography; PET = Positron Emission Tomography. 
 


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2.4.2. 
 Benefit Assessment 
The study population enrolled in this study has a high-unmet medical need. Participants 
failing multiple lines of prior treatments do not have many therapeutic options left, and if 
response can be achieved with currently available drugs, it is usually of short duration. 
This study is being performed to study safety and pharmacokinetics data in participants 
who have been previously treated with multiple agents, including alkylator, PI and 
immunomodulatory imide drug.  
Data from single-agent study BMA117159 support further evaluation of participants with 
MM failing currently available treatments. 
Based on the available clinical data, and since 2.5 mg/kg has been selected as the 
recommended dose in the belantamab mafodotin clinical development program, (and as 
the dose approved in the U.S.A. and Europe), the 3.4 mg/kg dose may not be used in this 
study. 
2.4.3. 
Overall Benefit: Risk Conclusion 
Considering the measures taken to minimize risk to participants, the potential risks 
associated with belantamab mafodotin are justified by the anticipated benefits that may 
be afforded to participants with RRMM. 
3. 
OBJECTIVES AND ENDPOINTS 
Objectives  
Endpoints 
Primary Objectives 
• 
To determine safety and tolerability 
of belantamab mafodotin in Chinese 
Participants with RRMM  
• 
Adverse events (AE), i.e., number (%) of 
participants with DLTs, number (%) of 
participants with AEs 
Secondary Objectives 
• 
To evaluate PK profile of 
belantamab mafodotin in Chinese 
Participants with RRMM 
• 
ADC, total antibody and cys-mcMMAF PK 
parameters following IV single and repeat dose 
administration during dose escalation as data 
permit (e.g., AUC, Cmax, tmax) 
• 
To evaluate safety and tolerability of 
belantamab mafodotin 
• 
Changes in clinical signs and laboratory 
parameters, ocular findings on ophthalmic 
exam 


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Objectives  
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x
To evaluate the clinical measures of 
efficacy of belantamab mafodotin 
x
ORR, defined as the percentage of participants 
with a confirmed partial response (PR) or 
better (i.e., VGPR, CR and stringent complete 
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4.1.1. 
Planned Dose Levels 
Projected dose levels are 2.5 mg/kg and 3.4 mg/kg. De-escalation to 1.9 mg/kg will be 
allowed in case of ≥2 DLT at dose 2.5 mg/kg. No doses will be explored beyond 
3.4 mg/kg, the dose that is considered to be the Maximum Feasible Dose (MFD). 
Dose-escalation will follow a 3 + 3 dose-escalation procedure as shown in Table 2. 
Evaluation of available safety data from at least 3 participants that have completed a 
minimum of 21 days is required prior to defining a new dose level and to start the next 
dose cohort. There will be no intra-participant dose escalation. The first 3 participants in 
2.5 mg/kg dose group will receive the study treatment sequentially with an observation 
window of 7 days, to observe acute toxicities. If the participating investigator and the 
coordinating investigator see no potential safety concerns from the first participant, the 
participating investigator and the coordinating investigator may recommend to enrol the 
next participant. Participants should not be enrolled at a higher dose level until at least 3-
6 participants in the previous dose cohort complete 21 days of post-dose assessment.  
Table 2 
3 + 3 Dose-Escalation Guidelines 
Number of Participants with DLT at a Given 
Dose Level 
Action 
0 out of 3 Participants 
Escalate to next dose level and enter 3 Participants 
1 out of 3 Participants 
Accrue 3 additional evaluable Participants at 
current dose level for a total of 6 evaluable 
Participants 
• 
If 0 of the 3 Participants experience a 
dose-limiting toxicity (DLT), proceed to 
next dose level. 
• 
If 1 or more Participants experience a 
DLT, dose will be de-escalated to 1.9 
mg/kg if the current dose cohort is 2.5 
mg/kg, otherwise the dose-escalation is 
stopped and this dose is declared the 
maximum tolerated dose (MTD). 
1 out of 6 Participants 
Escalate to next dose level 
2 or more Participants in a dosing cohort (up to 6 
Participants) 
Dose will be de-escalated to 1.9 mg/kg if the 
current dose cohort is 2.5 mg/kg, otherwise dose-
escalation will be stopped. At this dose level, the 
MTD has been exceeded (highest dose 
administered). 
Up to 6 participants will be enrolled into each of these dose levels with the above dose 
escalation rule followed.  
 
As per current available safety and efficacy information of belantamab mafodotin studies, 
the 3.4 mg/kg dose cohort is converted to an optional cohort in the dose-escalation study 
design. Escalation may not proceed if not supported by emerging clinical data from other 
belantamab mafodotin studies. 
 


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medical need in China, for whom there is no approved treatment options. Given the 
clinical activity demonstrated in the BMA117159 study, the treatment with belantamab 
mafodotin might offer a benefit to this participant 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 RRMM population in China.  
BMA117159 study has evaluated the safety and tolerability of belantamab mafodotin at 
doses ranging from 0.03 mg/kg IV up to 4.6 mg/kg IV. Belantamab mafodotin was well 
tolerated with no DLTs up to 4.6 mg/kg q3w; MTD was not reached, however, there was 
limited tolerability of the 4.6 mg/kg dose (prolonged fever, headache, severe fatigue). 
The maximum clinical benefit (ORR 60%) 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. Based on these 
data, GSK has initiated Study 205678, a global phase II study evaluating the safety and 
efficacy of belantamab mafodotin monotherapy (3.4 and 2.5 mg/kg administered once 
every 3 weeks) in participants with relapsed / refractory multiple myeloma.  
As the safety profile of belantamab mafodotin is established in a predominantly 
Caucasian MM population, the primary objective of study 208465 is to evaluate safety 
and confirm appropriate dose for Chinese MM population. Given that there is no apparent 
evidence showing racial difference in MM and BCMA expression between Chinese and 
Western populations, global Phase II study selected dose (2.5 and 3.4 mg/kg) will be 
investigated in study 208465. 
4.3. 
Justification for Dose 
4.3.1. 
Belantamab Mafodotin Starting Dose Justification 
The starting dose for belantamab mafodotin will be 2.5 mg/kg administered intravenously 
once every 3 weeks (Q3W) on Day 1 of each 21-day Cycle. The FTIH study tested doses 
up to 4.6 mg/kg, and global Phase II study selected 2.5 and 3.4 mg/kg for investigation in 
Study 205678. Currently there is no apparent evidence showing racial difference in MM 
and BCMA expression between Chinese and Western populations. However, PK 
difference may exist, as body weight usually affects clearance (CL) of monoclonal 
antibodies. Belantamab mafodotin dosing is adjusted by body weight. Thus, exposure 
difference is estimated low. 
The starting dose is selected because of the following reasons. 
• A starting dose lower than 2.5 mg/kg will have lower probability of getting 
clinical benefits based on the dose-response relationship in BMA117159. Also, 
the starting dose of 2.5 mg/kg had an acceptable safety profile in FTIH trial.  
• De-escalation to 1.9 mg/kg will be allowed in case of ≥2 DLT at dose 2.5 mg/kg. 
Although AEs leading to dose reduction started from 0.96 mg/kg in BMA117159, careful 
dose escalation and monitoring will be implemented to ensure participants’ safety 
throughout the study. 


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4.4. 
End of Study Definition 
The end of study is defined as when all participants have progressed, died, withdrawn 
consent, discontinued treatment due to other reasons, or have been lost to follow-up. 
A participant will be considered to have withdrawn from the study if any of the following 
apply: 
• The participant is lost to follow-up. 
• The participant has withdrawn consent. 
• The participant is no longer being followed at the investigator's discretion. 
• 
The study is closed or terminated. 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is 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 
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. Histological or cytologically confirmed diagnosis of MM as defined according to 
IMWG, 2014 criteria [Rajkumar, 2014] and 
a. Has undergone autologous stem cell transplant or transplant is considered 
not feasible by local assessment. 
b. Has failed at least 2 prior lines of anti-myeloma treatments, containing 
ALL of the following classes of drugs: alkylating agent, 
immunomodulatory imide drug and PI.  
c. In addition, eligible participant needs to be refractory to an 
immunomodulatory imide drug  (i.e., lenalidomide or pomalidomide), and 
to a proteasome inhibitor (i.e., bortezomib, ixazomib or carfizomib) as 
defined by IMWG criteria.  
d. Participants who failed with CD38 antibody (i.e., daratumumab) in 
previous clinical trials can also be considered to include if they meet the 
remainder of inclusion criteria in this protocol. 
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 


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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 functions as defined in Table 3 
Table 3 
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 
eGFR1 
Spot urine (albumin/creatinine ratios (spot urine) 
30 mL/min/ 1.73 m1  
<500 mg/g (56 mg/mmoL) 
Cardiac 
LVEF (Echo) 
25%2 
1. 
As calculated MDRD equation (Appendix 8) 
2. 
It is acceptable to use an existing ECHO result, if performed within three months of screening. For participants 
with abnormal LVEF (per institutional standards), the participant is to follow-up with a cardiologist. For 
participants with low LVEF (per institutional standards), consider referring to cardiology per local standards of 
care. 
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. 


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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 4 months after the last dose of study treatment 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 treatment. 
 
A WOCBP must have a negative highly sensitive serum pregnancy test within 72 
hours of dosing on C1D1 and agree to use effective contraception during the study 
and for 4 months after the last dose of study treatment.  
 
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 from the 
time of first dose of study until 6 months after the last dose of study treatment to 
allow for clearance of any altered sperm:  
• Refrain from donating sperm 
PLUS either: 
• Be abstinent from heterosexual intercourse as their preferred and usual 
lifestyle (abstinent on a long term and persistent basis) and agree to remain 
abstinent.  
OR 
• Must agree to use contraception/barrier as detailed below: 
Agree to use a male condom, even if they have undergone a successful 
vasectomy and female partner to use an additional highly effective 
contraceptive method with a failure rate of <1% per year 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 5.0 must 
be ≤Grade 1 at the time of enrolment except for alopecia and Grade 2 peripheral 
neuropathy. 


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5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
1. Systemic anti-myeloma therapy within <14 days, or plasmapheresis within 7 days 
prior to the first dose of study drug 
2. Symptomatic amyloidosis, active POEMS syndrome (polyneuropathy, 
organomegaly, endocrinopathy, myeloma protein, and skin changes), active 
plasma cell leukemia at the time of screening. 
3. Prior allogeneic stem cell transplant (SCT)  
4. Current corneal epithelial disease except mild punctate keratopathy  
5. 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.  
6. Evidence of active mucosal or internal bleeding 
7. Any major surgery within the last four weeks 
8. 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. 
9. 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.  
10. 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. 
11. 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).  
12. Evidence of cardiovascular risk including any of the following: 


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a) QTcF interval >480 msecs (the QT interval values must be corrected 
for heart rate by Fridericia’s formula [QTcF]) 
b) Evidence of current clinically significant untreated arrhythmias, 
including clinically significant ECG abnormalities such as 2nd degree 
(Mobitz 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 three 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 severe hypertension, e.g. 170/110 
13. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs 
chemically related to belantamab mafodotin, or any of the components of the 
study drug. 
14. Pregnant or lactating female. 
15. Active infection requiring antibiotic, antiviral, or antifungal treatment. 
16. Known HIV infection. 
17. 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) 
18. 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. 
5.3. 
Lifestyle Considerations 
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 includes demography, screen 
failure details, eligibility criteria, and any serious adverse events (SAEs). 


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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. 
STUDY TREATMENT 
Study treatment is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
6.1. 
Study treatment(s) Administered 
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 over 30-60 minutes.  
Product name: 
Belantamab Mafodotin for Injection 
Dosage form: 
Belantamab mafodotin for Injection: 100 mg/vial 
Unit dose strength(s)/Dose 
Level(s): 
Belantamab mafodotin for Injection: 100 mg/vial. Dosage(s): 2.5 mg/kg, or 
3.4 mg/kg 
 
Route/ 
Administration/ Duration: 
Delivered as IV solution over 30-60 min (Section 6.1.1) 
Dosing instructions: 
Belantamab mafodotin for Injection: Reconstitute belantamab mafodotin 
lyophilized powder 100 mg/vial with water for injection (WFI) before use  
Manufacturer/ Source of 
Procurement: 
GSK 
  
6.1.1. 
Belantamab Mafodotin Treatments Administered 
Belantamab mafodotin will be administered to participants intravenously as mg/kg 
calculated dose at the study site. The dose to be administered will be calculated using 
actual body weight at baseline and may be reduced for toxicity according to protocol 
guidelines. It is recommended to prime the IV tubing with at least 15 mL prior to dosing. 
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 over approximately 
30- 60 minutes. 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 4. 


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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 unacceptable toxicity 
(Section 7).  
6.2. 
Preparation/Handling/Storage/Accountability 
a. 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. 
b. 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. 
c. 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). 
d. Further guidance and information for the final disposition of unused study 
treatment are provided in the SRM. 
e. 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 
and/or GSK study contact. 
f. 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. 
6.3. 
Measures to Minimise Bias: Randomization and Blinding 
This is an open-label, non-randomized study. 
6.4. 
Study treatment Compliance 
Belantamab mafodotin will be intravenously administered to participants at the study site. 
The dose to be administered is based on body weight calculation and may be reduced for 
toxicity according to protocol guidelines. 
Administration will be documented in the source documents and reported in the 
electronic case report form (eCRF). The time of start and end of infusion will be 
documented in eCRF. 


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6.5. 
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. 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. 
6.5.1. 
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 control or stability control.  
6.5.2. 
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. 
Administration of live or live-attenuated vaccines are contraindicated 30 days prior to the 
first dose of study treatment and while on study treatment. Use of live or live-attenuated 
vaccines is further contraindicated for at least 70 days following the last dose of 
belantamab mafodotin.  Killed or inactivated vaccines may be administered; however, the 
safety and response to such vaccines cannot be predicted. 


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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), OATP1B1, and OATP1B3 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. 
6.5.3. 
Prohibited Device(s) 
Contact lenses are prohibited while the participant is receiving belantamab mafodotin. 
Following discontinuation of belantamab mafodotin treatment, contact lens use may be 
restarted after a qualified eye care specialist (Appendix 9) confirms that there are no other 
contraindications. 
 
6.6. 
Dose Modification 
Table 4 details the permitted dose modifications of belantamab mafodotin.  Table 5 and 
Table 6 contain dose modification guidance for drug-related AEs.  See Table 7 for dose 
modification guidelines for belantamab mafodotin treatment-related changes in vision. 
Table 4 
Permitted Dose Reductions 
Starting dose 
Dose reduction 
2.5 mg/kg 
1.9 mg/kg 
3.4 mg/kg 
2.5 mg/kg, 1.9 mg/kg 
 
If the participant cannot tolerate the drug after the allowed dose reduction of belantamab 
mafodotin to the lowest allowed dose of 1.9 mg/kg, he or she must discontinue treatment 
for lack of tolerability. 
In case of full resolution of symptoms which lead to dose reduction, further treatment at 
the previous dose level may be considered by the investigator.  
If a dose is delayed, the participant should wait for the next scheduled dose to resume 
treatment. In individual cases where in the judgment of the Investigator waiting a full 
cycle to resume treatment after delay (skipping dose) related to toxicity which has 
resolved would be detrimental to the participant’s health, the PI should contact the 
Medical Monitor to discuss an earlier re-start. An earlier re-start may be considered only 
for participants who have recovered from toxicity to at least ≤Grade 1. The dosing with 
belantamab mafodotin cannot occur more frequently than every 21 days (±3-day 


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window). In such cases, efficacy and safety assessments must remain 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). Evaluations associated with a dose would 
be entered into the eCRF under the next scheduled cycle.  
Resuming treatment with belantamab mafodotin will be possible with or without dose 
reduction after the toxicity has resolved to Grade 1 or less.  


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Table 5 
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 or 
absolute increase by 
3 mg/dL 
>3.0 mg/dL from 
baseline 
or 
3.0xULN 
• 
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 
current 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  
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 
Urine Dipstick 
2+ 
• 
May continue belantamab mafodotin dosing 
• 
Confirm by quantitative assessment using 
albumin/creatinine (spot urine from first void) 
• 
If albumin/creatinine >2000 mg/g, at the next cycle 
follow guidance above for Spot Urine. 
3+ 
• 
Interrupt treatment and follow up for recovery. 
Implement quantification of albumin/creatinine ratio 
Thrombocytopenia  
(on days of dosing)  
Grade 3 
• 
No bleeding: continue treatment with 1 dose level 
reduction. Consider reverting to previous dose once 
thrombocytopenia recovered to Grade 2 or less 
• 
With bleeding: withhold the dose, continue treatment 
after recovery with 1 dose level reduction 
• 
Consider additional supportive treatment (e.g., 
transfusion), as clinically indicated and per local 
practice. 
Grade 4 
• 
Withhold the dose. Consider restarting with 1 dose 
level reduction if recovered, or transfused to ≤Grade 
3 only if there is no active bleeding at time of 
treatment restart 
• 
If thrombocytopenia is considered disease related, is 
not accompanied by bleeding, and recovers with 
transfusion to >25x109/L continuing treatment at 1 
dose level reduction may be considered after 
discussion with the Medical Monitor 


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Toxicity 
Grade/description 
of toxicity 
Recommendations for Belantamab Mafodotin 
Febrile neutropenia 
Defined as: single 
temp of 38.3°C, or 
sustained 38°C for 
>1 h AND ANC 
<1.0×109/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) 
on Day 1 of the subsequent cycle. 
• 
Prophylactic antibiotics, per physician discretion and 
local institutional guidance. Consider growth factors. 
• 
Local guidance must be followed for hematological 
monitoring, if more conservative than the protocol 
SoA specifications. 
• 
In cases of frequent recurrent neutropenia (ANC 
<1.0x109/L), consider dose reduction of belantamab 
mafodotin by 1 level  
 
Infusion Reactionb 
2 
• 
Stop the infusion, provide medical treatment and 
continue at half the original infusion rate after 
resolution to Grade 0-1. Any future infusion needs to 
be pre-medicated. 
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 from study treatment 
Pneumonitis 
2 
• 
Withhold treatment with belantamab mafodotin 
• 
Upon recovery, restart treatment with 1 dose level 
reduction.  
• 
If patient is already at the lowest dose level 
(1.9 mg/kg), then rechallenge with the same dose 
must be discussed with the Medical Monitor  
Grade 3-4 
• 
Permanently discontinue from treatment 
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 6 
General Dose Modification and Management Guidelines for Drug- 
related Adverse Events Not Otherwise Specified 
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: 
• 
Delay study drug, 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 study 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 study 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. 
 
 
 


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Grade/description of toxicity (as described in 
NCI-CTCAE ver. 5.0) 
Recommendations 
Continue treatment at current dose. 
Dose reduce by 25% (either to 2.5 or to 1.9 mg/kg) 
and continue treatment.  
x
If already on 1.9 mg/kg, participant continues 
treatment at same dose.  
Upon resolution (e.g., Grade 1), re-escalation to 
previous dose may be considered. 
Hold treatment and allow to recover to Grade ≤2.  
Once recovered, dose reduce to 2.5 or to 1.9 mg/kg.  
x
If already on 1.9 mg/kg, participant continues at 
same dose. 
If after event resolution eye symptoms are considered 
stable for at least 3 cycles and if vision is Grade ≤1, 
consider re-escalation (to 3.4 or 2.5 mg/kg). 
Hold treatment and allow to recover to Grade ≤2.  
Restart only after discussion with Medical Monitor for 
participants whose vision improves to Grade ≤2. If 
restart approved, once recovered to Grade ≤2, dose 
reduce to 2.5 or 1.9 mg/kg. If already on 1.9 mg/kg, 
participant continues at same dose. 
 
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therefore have been excluded.
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have their ophthalmologic exams decreased to once every 3 months. In case of persistent 
ocular exam findings, newly developed ocular symptoms or vision changes, further 
ocular exams should be performed at least every cycle until resolution (to Grade 1 or 
baseline) or more frequently as clinically indicated by the qualified eye care specialist 
(Appendix 9). See Section 8.3.9 for the list of ophthalmic exam procedures.  
Participants who have ocular symptoms at end of study treatment will continue to be 
followed as indicated in the SoA (Section 1.3) for up to 12 months, or until full resolution 
of findings: defined as a return to participant’s baseline, or until deemed clinically stable 
by an ophthalmologist (or an optometrist if an ophthalmologist is not available), 
whichever comes first. Clinically stable is defined as changes less than or equal to 
Grade 1 as per Table 7.  
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 EOT.  Allow at least 5-10 minutes 
between administration of artificial tears and steroid eye drops (if administered).  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 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 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. 
Prophylactic or therapeutic corticosteroid eye drops are not required but can be used if 
clinically indicated. An ophthalmology (or optometry, if ophthalmology is not available) 
consult is required for all participants who require steroid eye drops for more than 7 days. 
Participants must avoid the use of contact lenses during the study. An 
ophthalmology/optometry consult is required for all participants who develop signs or 
symptoms of corneal toxicity.  
A summary of prophylactic interventions for corneal toxicity associated with belantamab 
mafodotin is provided in Table 8. 
 
 
 
 


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Table 8 
Prophylactic measures for corneal toxicity 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. Allow 5-10 minutes 
between administration of artificial tears 
and steroid eye drops (if administered) 
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 6.6 
 
6.7. 
Intervention after the End of the Study 
The investigator is responsible for ensuring that consideration has been given to the 
post-study care of the participant’s medical condition.  
Refer to Section 8 and the SOA (Table 1) for follow-up assessments of participants who 
are to be followed for disease progression after they permanently discontinue from study 
treatment.  
7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1. 
Discontinuation of Study Treatment 
Participant will receive study treatment until disease progression, death or unacceptable 
toxicity (including but not restricted to meeting stopping criteria for significant toxicity as 
outlined in Section 6.6), loss to follow-up, or end of study (Section 4.4).  
The study treatment must be permanently discontinued for any of the following reasons: 
• 
disease progression or unacceptable toxicity (including protocol-defined safety 
stopping criteria) 
• 
Pregnancy 
Study treatment may be permanently discontinued for any of the following reasons: 
• 
deviation(s) from the protocol 
• 
request of the participant or proxy (withdrawal of consent by participant or 
proxy) 
• 
Investigator’s discretion 
• 
concurrent illness that prevents further administration of study treatment(s) 
• 
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• 
study is closed or terminated.  
 
The primary reason of 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 must be 
recorded as the primary reason for permanently discontinuation on the eCRF. 
Once a participant has permanently discontinued from study treatment, the participant 
will not be allowed to re-enter the study. 
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 PD after study as specified in the SoA (Table 1).  
PD 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: 
• 
Progression is documented, or 
• 
New anti-cancer therapy is initiated, or 
• 
Lost to follow-up, or 
• 
Withdrawal of consent, or 
• 
Death occurs, or 
• 
End of study (Section 4.4) 
7.1.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology. 
Discontinuation of study treatment for abnormal liver tests is required when: 
• a participant meets one of the conditions outlined in the Figure 2 
OR 
• when in the presence of abnormal liver chemistries not meeting protocol-specified 
stopping rules, the investigator believes study treatment discontinuation is in the 
best interest of the participant.  


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Figure 2 
Phase I Liver Chemistry Stopping and Increased Monitoring 
Algorithm for Participants WITH entry criteria ALT ≤2.5xULN 
 
 
 
Liver Safety Required Actions and Follow up Assessments Section can be found in 
Appendix 5. 
7.1.1.1. 
Study treatment Restart or Rechallenge after liver stopping criteria met 
If participant meets liver chemistry stopping criteria do not restart/rechallenge participant 
with study treatment unless: 
• 
GSK Medical Governance approval is granted 
• 
Ethics and/or IRB approval is obtained, if required, and 
• 
Separate consent for intervention restart/rechallenge is signed by the participant 
Refer to Appendix 5 for details.  
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. 


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7.1.2. 
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 permanently discontinue study treatment but 
will continue in the study.  
7.1.3. 
Stopping Criteria Based on Ocular Examination Findings 
Belantamab mafodotin dose modifications and stopping criteria for treatment-related 
changes in visual acuity are detailed in Table 7, according to CTCAE criteria (Version 
5.0, 2017).  Participants who develop a Grade 4 event should be discussed with the GSK 
Medical Monitor to determine whether the participant can be allowed to continue 
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 7). 
7.1.4. 
Infusion-Related Reaction Stopping Criteria 
Premedication is not required prior to infusion unless deemed medically appropriate by 
the investigator following evaluation of IRRs. Premedication should be considered in any 
participant who experienced an IRR at first or any subsequent infusion with belantamab 
mafodotin. 
Infusion related reactions should be managed by guidelines provided in Table 5. A 
participant that experiences a Grade 4 IRR must permanently discontinue study treatment 
but will continue in the study. 
7.2. 
Participant Discontinuation/Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioural, 
compliance or administrative reasons.  
At the time of discontinuing from the study, if possible, an early discontinuation visit 
should be conducted. See SoA for data to be collected at the time of study discontinuation 
and follow-up and for any further evaluations that need to be completed. 
If the participant withdraws consent for disclosure of future information, the sponsor may 
retain and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the investigator must document this in the site study records. 
Withdrawn participants will not be replaced.  
7.3. 
Lost to Follow Up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  


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The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit 
as soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 
• 
Before a participant is deemed lost to follow up, the investigator or designee 
must make every effort to regain contact with the participant (where possible, 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, he/she will be considered to 
have withdrawn from the study.  
Discontinuation of specific sites or of the study as a whole are handled as part of 
Appendix 1. 
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 Appendix 2. 
Whenever vital signs, 12-lead electrocardiograms (ECGs) and blood draws are scheduled 
for the same nominal time, the assessments must occur in the following order: 12-lead 
ECG, vital signs, blood draws. The timing of the assessments must allow the blood draw 
to occur at the exact nominal time. Detailed procedures for obtaining each assessment are 
provided in the SRM. 
• 
Study procedures and their timing are summarised in the SoA.  
• 
Protocol waivers or exemptions are not allowed  
• 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the 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 utilised for screening or 


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baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA. 
• 
Visit Windows: 
• 
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 
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. 
• 
An ECHO completed within 3 months prior to screening can be used as a 
screening value. 
• 
Imaging applicable for participants with extramedullary disease must be 
completed within 30 days prior to first dose. . 
On study visits have a ±3-day window and PD follow-up visits have a ±7-
day window. 
• 
Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples. 


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8.2. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. 
8.2.1. 
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. 
8.2.2. 
Vital Signs 
Vital sign measurements must include systolic and diastolic blood pressure, temperature, 
and heart 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. 
8.2.2.1. 
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 1.3) 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. 
8.2.2.2. 
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 1.3) Participants may be 
discharged after the infusion has been completed if considered clinically stable and all 
other study procedures have been completed.  
8.2.3. 
Electrocardiograms 
12-lead electrocardiogram (ECGs) must be obtained in triplicate at designated time points 
and as single assessments at other time points as specified in the Schedule of Activities 
(Section 1.3). The ECG machine must automatically calculate the heart rate and measure 
PR, QRS, QT, and corrected QT (QTc) intervals. At each assessment, a 12-lead ECG 
must be performed by qualified personnel at the site after the participant has at least a 5-
minute rest.  
The QT interval must be corrected for heart rate by Fridericia’s formula (QTcF). Refer to 
the SRM for details regarding ECG procedures. 


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8.2.4. 
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. 
8.2.5. 
Clinical Safety Laboratory Assessments 
• 
Refer to Appendix 2 for the list of clinical laboratory tests to be performed and 
to the SoA for the timing and frequency.  
• 
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 considered clinically significantly abnormal 
during participation in the study or within 30 days after the last dose of study 
treatment should be repeated until the values return to normal or baseline or are 
no longer considered significantly abnormal by the investigator or medical 
monitor.  
• 
If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor 
notified. 
• 
All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the laboratory manual and the SoA.  
8.2.6. 
ECOG Performance Status 
Participant performance status will be assessed at Screening, using the Eastern 
Cooperative Oncology Group (ECOG) scale, provided in Appendix 7. 
8.2.7. 
Visual Function Questionnaire 
The impact of potential ocular toxicity on function and health-related quality-of-life will 
be assessed with the use of a visual function questionnaire, the OSDI.  All participants 
will use the Self-Administered version of the questionnaire, 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 assessments conducted via 
telephone (either during participation in the treatment period or during Follow-up), the 
Interviewer Administered format must be used.  


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The OSDI will be administered to participants in different regions based on the 
availability of translated versions. 
8.2.7.1. 
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. 
8.3. 
Adverse Events and Serious Adverse Events 
The definitions of an AE or SAE can be found in Appendix 3. 
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study treatment or the study, 
or that caused the participant to discontinue the study treatment (see Section 6).  
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All SAEs will be collected from signing of the ICF until 70 days following 
discontinuation of study treatment regardless of initiation of a new cancer 
therapy or transfer to hospice at the time points specified in the SoA (Table 1). 
However, any SAEs assessed as related to study participation (e.g., study 
intervention, protocol-mandated procedures, invasive tests, or change in existing 
therapy) or related to a GSK product will be recorded from the time a participant 
consents to participate in the study up to and including follow up. 
• 
All AEs will be collected from the start of treatment until 70 days following 
discontinuation of study treatment regardless of initiation of a new cancer 
therapy or transfer to hospice at the time points specified in the SoA. 
• 
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 3. 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 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. 


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8.3.2. 
Method of Detecting AEs and SAEs 
• 
The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
Appendix 3. 
• 
Care will be taken not to introduce bias when detecting AE and/or SAE. Open-
ended and non-leading verbal questioning of the participant is the preferred 
method to inquire about AE occurrence.  
8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, non-serious AEs of special interest, 
will be followed until the event is resolved, stabilised, otherwise explained, or the 
participant is lost to follow-up (as defined in Section 7.3). Further information on follow-
up procedures is given in Appendix 3. 
8.3.4. 
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. 
8.3.5. 
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. 
• 
Details of all pregnancies in female participants will be collected after the 
start of study treatment and for 8 months following last dose of belantamab 
mafodotin. 


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• 
Details of all pregnancies for female partners of male participants will be 
collected after the start of study treatment and 5 months following last dose 
of belantamab mafodotin. 
• 
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 4. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, and ectopic pregnancy) are considered 
SAE. 
 
8.3.6. 
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 3 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. 
8.3.7. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs 
An event which is part of the natural course of the disease under study (i.e., disease 
progression or hospitalization due to 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. 
8.3.8. 
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 scale provided in Table 7. 
Guidelines for dose modifications and interruptions for management of common 
toxicities associated with the study treatment(s) are provided in Table 4. Dose 
modifications for belantamab mafodotin corneal events will be based on the GSK scale 
for corneal events in Table 7. 


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8.3.9. 
Ocular Examinations and Procedures 
Participants will be assessed by ophthalmologist (or an optometrist if an ophthalmologist 
is not available) at screening/baseline.  
A full screening/baseline ophthalmic examination for all participants must include for 
both eyes (OU): 
a. Best corrected visual acuity  
b. Documentation of manifest refraction and the method used to obtain best 
corrected visual acuity 
c. Current glasses prescription (if applicable) 
d. Intraocular pressure measurement  
e. Full anterior segment (slit lamp) examination including fluorescein staining of the 
cornea. Anterior segment exam includes: conjunctiva, sclera, cornea, lens and 
anterior vitreous 
f. Dilated funduscopic exam 
The on treatment and follow-up ophthalmic exam should be performed for both eyes 
(OU) as described below and in the SoA (Section 1.3):  
1. Best corrected visual acuity 
2. Documentation of manifest refraction and the method used to obtain best corrected 
visual acuity. 
3. Intraocular pressure measurement (if clinically indicated). 
4. Anterior segment examination of the: conjunctiva, sclera, cornea (including 
fluorescein staining) and lens 
The end of study treatment and last follow-up ophthalmic exam, if required, should match 
the screening/baseline exam. 
Additional examinations should be performed at the discretion of the treating eye 
specialist. 
8.4. 
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 
belantamab mafodotin can no longer be detected systemically (at least 3 
months). 


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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Statistical Hypotheses 
Due to limited sample size and the purpose of the study, no formal statistical hypotheses 
are being tested. Primary objective of the study is to determine safety and tolerability of 
belantamab mafodotin in Chinese Participants with RRMM. Analysis of the data will 
only utilise descriptive methods. 
9.2. 
Sample Size Determination 
The sample size planned arises from the predefined dose escalation criteria for dose 
selection and is not driven by statistical considerations. Based on the 3+3 dose escalation 
design the anticipated size will be up to 6 evaluable participants for each cohort and the 
actual numbers will depend on the safety observed. 
9.3. 
Populations for Analyses 
The ‘All Treated Population’ is defined as all eligible participants who receive at least 1 
dose of study treatment. An incorrect treatment schedule or drug administration or an 
early termination of treatment will not result in exclusion of participants from this 
population.  
The ‘DLT Evaluable Population’ is defined as all the eligible participants who have 
received the 1st dose as planned, and experienced a DLT during the cycle 1 or completed 
the cycle 1. Participants who have been replaced during cycle 1 will be excluded from the 
DLT evaluable population. 
The ‘PK Population’ is defined as those participants in the “All Treated” population 
from whom at least one PK sample was obtained, analyzed, and was measurable. 
9.4. 
Statistical Analyses 
9.4.1. 
Key Elements of Analysis Plan 
Data will be listed and summarized according to the GSK reporting standards, where 
applicable. If data warrant, the response data will be summarized by dose level. Complete 
details will be documented in the Reporting and Analysis Plan (RAP). Any deviations 
from, or additions to, the original analysis plan described in this protocol will be 
documented in the RAP and clinical study report. 
Due to very small numbers per center, data from all participating centers will be pooled 
prior to analysis. 
Demographic and baseline characteristics will be summarized. 


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9.4.2. 
Dose Limiting Toxicity 
The DLT Evaluable Population will be used for evaluation of the number of participants 
experiencing any DLTs of each cohort. 
For primary statistical analysis, the number and proportion of participants in the DLT 
population who experienced DLT during the Cycle 1 of study treatment will be presented 
by dose level.  
9.4.3. 
Safety Analyses 
The All Treated Population will be used for the analysis of safety data (except the DLT 
analysis). All serially collected safety endpoints will be summarized according to the 
scheduled, nominal visit at which they were collected and across all on-treatment time 
points using a “worst-case” analysis. Complete details of the safety analyses will be 
provided in the Reporting and Analysis Plan (RAP). 
9.4.4. 
Extent of Exposure 
The number of participants in all treated population will be summarized according to the 
duration of therapy.  
9.4.5. 
Adverse Events 
Adverse events (AEs) will be coded using the standard MedDRA. Severity of corneal 
events will be graded using the scale provided in Table 7. The severity of other adverse 
events (AEs) will be graded by the investigator according to the National Cancer 
Institute- Common Toxicity Criteria for Adverse Events (NCI-CTCAE) (version 5.0). 
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, serious adverse events (SAEs) and AEs leading to discontinuation of study 
treatment. Adverse events (AEs), if listed in the NCI-CTCAE (version 5.0) will be 
summarized by the maximum grade. Otherwise, the AEs will be summarized by 
maximum intensity. 
The incidence of deaths and the primary cause of death will be summarized. 
9.4.6. 
Clinical Laboratory Evaluations 
Hematology and clinical chemistry data will be summarized using frequencies and 
proportions according to National Cancer Institute-Common Toxicity Criteria for 
Adverse Events (NCI-CTCAE) (version 5.0). Laboratory test results outside the reference 
ranges that do not have associated NCI-CTCAE criteria will be summarized using 
proportions.  
9.4.7. 
Immunogenicity Analyses 
For each participant, the results and titers of anti-belantamab mafodotin binding 
antibodies will be listed for each assessment time point with the time-matched 


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of participants enrolled in this study as described in the Dose Escalation Plan. The DEC 
will be chaired by the GSK medical monitor and membership will include a GSK clinical 
scientist, GSK safety physician, GSK statistician, GSK pharmacokineticist, along with 
additional GSK staff as appropriate and all participating investigators.  
The DEC will review of relevant safety, PK, and PD data generated immediately after all 
participants treated in the same dose cohort have passed the DLT period.  
Dose Escalation Meetings will be scheduled at the conclusion of the DLT assessment 
period for participants enrolled in each cohort to review safety data and determine the 
next dose level appropriate for study.   
In addition, throughout the conduct of the study the DEC may decide to: 
1) Modify the dose escalation of belantamab mafodotin proposed by the 3+3 
model based on clinical judgement.  
2) Investigate alternative dosing regimens  
3) Modify the timing, frequency, and/or type of safety assessments 
performed during study conduct  
4) Approve continuation of belantamab mafodotin study therapy in 
participants who have experienced DLT provided the toxicity did not meet 
study discontinuation criteria and has resolved at the time of re-start.  
5) Request intervention of additional participants at previously completed 
dose levels for the purpose of obtaining additional safety, PK, PD, 
metabolite, or biomarker data (i.e. PK/PD/Metabolite). 
6) Halt enrolment into any cohorts as deemed appropriate based on emerging 
clinical data at any time during the trial. 
Dose escalation decisions will be made with DEC members after review of available 
safety data from at least one cycle of therapy with belantamab mafodotin. Available data 
will be provided to participants prior to each scheduled Dose Escalation Meeting. 
Attendees of Dose Escalation Meetings will include but not limited to DEC members. All 
dose escalation and safety decision will be documented in writing with copies maintained 
by GSK in the Trial Master File and submitted to each site for documentation. Decisions 
with potential impact on the safety of study participants (i.e., unfavorable change in 
risk/benefit assessment) will be promptly communicated to regulatory authorities and 
study sites as appropriate. 
As per current available safety and efficacy information of belantamab mafodotin studies, 
the 3.4 mg/kg dose cohort is converted to an optional cohort in the dose-escalation study 
design. Escalation may not proceed if not supported by emerging clinical data from other 
belantamab mafodotin studies. 
 


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10. 
REFERENCES 
Alley SC, Zhang X, Okeley NM, Anderson M, Law CL, Senter PD, et al. The 
pharmacologic basis for antibody-auristatin conjugate activity. J Pharmacol Exp Ther. 
2009;330(3):932-8. 
Belantamab mafodotin IB [GlaxoSmithKline Document Number RPS-CLIN-004867 
Report Date 14-MAY-2021. 
Dougherty BE, Nichols JJ, Nichols KK. Rasch analysis of the Ocular Surface Disease 
Index (OSDI). Invest Ophthalmol Vis Sci. 2011;52(12):8630-5. 
Eaton JS, Miller PE, Mannis MJ, Murphy CJ. Ocular Adverse Events Associated with 
Antibody-Drug Conjugates in Human Clinical Trials. J Ocul Pharmacol Ther. 2015 
;31(10):589-604 
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide 
burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893-917. 
International Agency For Research on Cancer, GLOBOCAN 2018: Estimated Cancer 
Incidence, Mortality and Prevalence Worldwide in 2018 Available at 
http://gco.iarc.fr/today/data/factsheets/populations/160-china-fact-sheets.pdf Accessed 
Sep-2018 
Jagannath SB. Barlogie JR. Berenson DS, Siegel D, Irwin PG, Richardson R, et al. 
Updated survival analyses after prolonged follow-up of the phase 2, multicenter CREST 
study of bortezomib in relapsed or refractory multiple myeloma. Br J Haematol. 
2008;143(4):537-540. 
Kim K, Lee JH, Kim JS, Min CK, Yoon SS, Shimizu K et al. Clinical profiles of multiple 
myeloma in Asia-An Asian Myeloma Network study. Am J Hematol. 
2014;89(7):751-756. 
Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. 
Annu Rev Immunol. 2013;31:51-72. 
Krysko DV, Garg AD, Kaczmarek A, Krysko O, Agostinis P, Vandenabeele P. 
Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer. 
2012;12(12):860-75. 
Langat DL, Wheaton DA, Platt JS, Sifers T, Hunt JS. Signaling pathways for B cell-
activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in human placenta. 
Am. J. Pathol. 2008; 172:1303-1311. 
Laurent SA, Hoffmann FS, Kuhn PH, Cheng Q, Chu Y, Schmidt-Supprian M, et al. 
gamma-Secretase directly sheds the survival receptor BCMA from plasma cells. Nat 
Commun. 2015;6:7333. 


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Li X, Wulfsohn MS, Koch GG. Considerations on testing secondary endpoints in group 
sequential design. Statistics in Biopharmaceutical Research. 2017 Oct 2;9(4):333-7. 
Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al. Targeting 
CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015; 373 
(13):1207-1219. 
Lonial S, Anderson KC. Association of response endpoints with survival outcomes in 
multiple myeloma. Leukemia. 2014;28(2):258-268. 
Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, Chari A, et al. Belantamab mafodotin 
for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomized, 
open-label, phase 2 study. Lancet Oncol. 2020:21:207-21. 
Moreau PJ, San Miguel P, Sonneveld MV, Mateos E, Zamagni H, Avet-Loiseau R, et al. 
Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and 
follow-up. Annals of Oncology. 2017;0:1-11. 
National Cancer Institute (NCI) CTCAE Version 5, 2017. Available at: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Q 
uick_Reference_5x7.pdf. 
National Comprehensive Cancer Network (2016) "Multiple Myeloma. Version 3.2017 - 
November 28, 2016." NCCN Clinical Practice Guidelines in Oncology (NCCN 
Guidelines), 58. 
Palumbo A and Anderson K. Multiple Myeloma. N Engl J Med. 2011; 364:1046-60. 
Pettit GR, Srirangam JK, Barkoczy J, Williams MD, Boyd MR, Hamel E, et al. 
Antineoplastic agents 365. Dolastatin 10 SAR probes. Anticancer Drug Des. 
1998;13(4):243-77. 
Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. 
International Myeloma Working Group updated criteria for the diagnosis of multiple 
myeloma. The Lancet Oncology. 2014;15: e538-e548 
Rajkumar SV. Multiple myeloma: 2011 update on diagnosis, risk stratification, and 
management. Am J Hematol. 2011b;86:57-65. 
Rajkumar SV. Treatment of multiple myeloma. Nat Rev Clin Oncol. 2011a;8:479-491. 
Rajkumar SV. Updated Diagnostic Criteria and Staging System for Multiple Myeloma. 
Am Soc Clin Oncol Educ Book. 2016;35:e418-23. 
Richardson, PG., Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. A 
phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med. 
2003;348(26):2609-2617. 


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Richardson, PG., Barlogie B, Berenson J, Singhal S, Jagannath S, Irwin D, et al. 
Extended follow-up of a phase II trial in relapsed, refractory multiple myeloma: final 
time-to-event results from the SUMMIT trial. Cancer. 2006;106(6):1316-1319. 
Schiffman RM, Christianson MD, Jacobsen G, Hirsch JD, Reis BL. Reliability and 
validity of the Ocular Surface Disease Index. Arch Ophthalmol. 2000;118(5):615-21. 
Siegel DS, Martin T, Wang M, Vij R, Jakubowiak AJ, Lonial S, et al. A phase 2 study of 
single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory 
multiple myeloma. Blood. 2012;120(14):2817-25. 
Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2016. CA Cancer J Clin. 2016;66:7-30. 
Tai YT, Anderson KC. Targeting B-cell maturation antigen in multiple myeloma. 
Immunotherapy. 2015;7(11):1187-99. 
Tai YT, Li XF, Breitkreutz I, Song W, Neri P, Catley L, et al. Role of B-cell-activating 
factor in adhesion and growth of human multiple myeloma cells in the bone marrow 
microenvironment. Cancer Res. 2006;66(13):6675-82. 
The Criteria Committee of the New York Heart Association (NYHA). Nomenclature and 
Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th Ed. Boston, Mass: 
Little, Brown & Co.; 1994:253-256 
Trudel S, Lendvai N, Popat R, Voorhees PM, Reeves B, Libby EN, et al. Antibody-drug 
conjugate, GSK2857916, in relapsed/refractory multiple myeloma: an update on safety 
and efficacy from dose expansion phase I study. Blood Cancer J. 2019;9:37. 


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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
11.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
11.1.1. 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with: 
• Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines 
• Applicable ICH Good Clinical Practice (GCP) Guidelines 
• Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, Investigator Brochure, and other 
relevant documents (e.g., advertisements) must be submitted to an IRB/IEC by 
the investigator and reviewed and approved by the IRB/IEC before the study is 
initiated.  
• 
Any amendments to the protocol will require 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, and all other 
applicable local regulations 
11.1.2. 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 


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11.1.3. 
Informed Consent Process 
• 
The investigator or his/her representative will explain the nature of the study to 
the participant or his/her legally authorised representative and answer all 
questions regarding the study.  
• 
Participants must be informed that their participation is voluntary. Participants 
or their legally authorised 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 authorised 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 authorised representative.  
• 
Participants who are rescreened are required to sign a new ICF. 
11.1.4. 
Data Protection 
• 
Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred.  
• 
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 authorised personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities. 
11.1.5. 
Dissemination of Clinical Study Data 
• 
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. 


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• 
The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with GSK Policy. 
• 
GSK intends to make anonymized participant-level data from this trial available 
to external researchers for scientific analyses or to conduct further research that 
can help advance medical science or improve participant care. This helps ensure 
the data provided by trial participants are used to maximum effect in the creation 
of knowledge and understanding 
11.1.6. 
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.  
• 
Monitoring details describing strategy (e.g., risk-based initiatives in operations 
and quality such as Risk Management and Mitigation Strategies and Analytical 
Risk-Based Monitoring), methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, 
or on-site monitoring) are provided in the Monitoring Plan. 
• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.  
• 
The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations). 
• 
Study monitors will perform ongoing source data verification to confirm that 
data entered into the CRF by authorised 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 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.  


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11.1.7. 
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 reported on the CRF or 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 
11.1.8. 
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 
11.1.9. 
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. 
 


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11.2. 
Appendix 2: Clinical Laboratory Tests 
Table 9 
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 carbon dioxide 
(CO2) 
Gamma glutamyl 
transferase (GGT) 
Albumin 
Sodium 
Calcium 
Alkaline phosphatase 
Total Protein 
Magnesium 
Phosphorous 
Creatine kinase (CK) 
LDH 
eGFR 
Spot urine (albumin / 
creatinine ratio)5, 6
 
 
Urine1 
Routine Urine Dipstick (Urinalysis required if blood or protein is detected by  dipstick)6 
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- according to 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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PK/ADA  
Pharmacokinetics (PK)2 
Anti Drug Antibodies (ADA)2, 3 
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 disease assessment1 
Bone marrow to confirm sCR by IHC1 
Bone marrow for FISH testing7  
Biomarker Measurements 
 
 
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. Urine dipstick for protein may be used to assess for presence of urine protein. Albumin/creatinine ratio needs to be 
done in any participant with urine dipstick result of ≥1+ (at Screening Visit), or ≥2+ (during study treatment), or with 
positive protein if urine dipstick protein quantification is not available. 
7. FISH testing at least for: t(4;14), t(14;16), 17p13del, and +1q21. BM samples from within 60 days prior to first dose 
are acceptable for FISH analysis. If not available from local laboratory, it can be performed at central laboratory. 
CCI
CCI


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11.3. 
Appendix 3: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
11.3.1. 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study treatment, whether or not considered 
related to the study treatment. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study treatment. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study treatment administration even 
though 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 should 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. 
 
11.3.2. 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
o Results in death 
o 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 should 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, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 


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Is a congenital anomaly/birth defect 
Other situations: 
• 
Medical or scientific judgment should 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 jeopardise the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should 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 5 for liver chemistry follow-up procedures. 
 
11.3.3. 
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 
• 
Valvulopathy 
• 
Pulmonary hypertension 
• 
Cerebrovascular events/stroke and transient ischemic attack 


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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or 
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2 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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11.3.5. 
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. 
 


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11.4. 
Appendix 4: 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 treatment, additional evaluation should be 
considered. 
Women in the following categories are not considered WOCBP 
1 
Premenarchal 
2 
Premenopausal female 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 female 
• 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high follicle stimulating hormone (FSH) level in 
the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or hormonal replacement therapy 
(HRT). However, in the absence of 12 months of amenorrhea, confirmation with 
more than 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 
• 
Vasectomised partner 
• 
Note: Vasectomised 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 treatment. 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 amenorrhoea 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 of a female partner of a 
male study participant who becomes pregnant while participating in this study, and 


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for 6 months following last dose of belantamab mafodotin. This applies only to male 
participants who receive study treatment. 
• 
After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the partner’s 
pregnancy.  
• 
The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to GSK 
• 
Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of fetal 
status (presence or absence of anomalies) or indication for procedure.  
Female Participants who become pregnant 
• 
Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study, for 4months following last dose 
of belantamab mafodotin.  
• 
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 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 treatment 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 
treatment.  
 


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11.5. 
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments and Study treatment Rechallenge Guidelines 
Phase I 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 
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 
• 
Immediately discontinue study 
intervention 
• 
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, stabilise, 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  
• 
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.  
• 
Obtain INR and recheck with each liver 
chemistry assessment until the 
aminotransferases values show downward 
trend 
• 
Blood sample for pharmacokinetic (PK) 
analysis, obtained within 45 days after last 
dose6 
• 
Serum creatine phosphokinase (CPK) and 
lactate dehydrogenase (LDH), gamma 
glutamyl transferase [GGT], glutamate 
dehydrogenase [GLDH], and serum albumin. 
• 
Fractionate bilirubin, if total bilirubin2xULN 
• 
Obtain complete blood count with differential 
to assess eosinophilia 


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MONITORING: 
If ALT≥3xULN AND total bilirubin 
2xULN or INR >1.5:  
 
• 
Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within 24 
hrs 
• 
Monitor participants twice weekly until liver 
chemistries resolve, stabilise or return to 
within baseline 
• 
A specialist or hepatology consultation is 
recommended 
 For All other criteria (bilirubin <2xULN 
and INR 1.5):  
 
• 
Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within 24-
72 hrs  
• 
Monitor participants weekly until liver 
chemistries resolve, stabilise or return to 
within baseline 
• 
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 intake case report form 
If ALT 3xULN AND total bilirubin 2xULN or 
INR >1.5 obtain the following in addition to the 
assessments listed above: 
 
• 
Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative total 
immunoglobulin G (IgG or gamma 
globulins). 
• 
Serum acetaminophen adduct assay should 
be conducted (where available) to assess 
potential acetaminophen contribution to liver 
injury unless acetaminophen use is very 
unlikely in the preceding week. (e.g., where 
the participant has been resident in the 
clinical unit throughout)  
• 
Liver imaging (ultrasound, magnetic 
resonance, or computerised tomography) 
and /or liver biopsy to evaluate liver disease; 
complete Liver Imaging and/or Liver Biopsy 
CRF forms. 
• 
Liver biopsy may be considered and 
discussed with local specialist if available, 
for instance: 
o In patients when serology raises the 
possibility of autoimmune hepatitis (AIH) 
o In patients when suspected drug-
induced liver injury (DILI) 
progresses or fails to resolve on 
withdrawal of study intervention 
o In patients with acute or chronic atypical 
presentation:  
• 
If liver biopsy conducted complete liver 
biopsy form. 
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that participant if ALT 3xULN and bilirubin 2xULN. 


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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 
PK 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. Instructions for sample handling and shipping 
are in the SRM.  
 
Phase I 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, stabilise 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, bilirubin 
<2xULN and INR 1.5, monitor participants twice 
monthly until liver chemistries normalise or return to 
within baseline. 
 
11.5.1. 
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) 


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• 
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. 
11.5.1.1. 
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.1 Clinical outcomes vary by drug with nearly 50% 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: 
• 
Hypersensitivity [Andrade, 2009] 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 rechallenges [Hunt, 2010; Papay, 2009]. 
• 
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.  


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• 
The participant must also provide signed informed consent specifically for the 
rechallenge- with study treatment. Documentation of informed consent must be 
recorded in the study 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 8.3.4. 
11.5.1.2. 
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 11.5.1.1 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. 


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• 
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 8.3.4. 
11.5.2. 
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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11.6. 
Appendix 6: International Myeloma Working Group Uniform 
Response Criteria for Multiple Myeloma (2016) 
Response 
Standard IMWG Criteria1 
sCR2 
• 
CR as defined below plus normal FLC ratio and absence of clonal plasma cells 
in bone marrow  by immunohistochemistry or 8-color, 2 tube multiparametric 
flow cytometry 
CR3 
• 
negative immunofixation of serum and urine and disappearance of any soft 
tissue plasmacytomas and <5% plasma cells in bone marrow aspirates3 
VGPR3 
• 
Serum and urine M-protein detectable by immunofixation but not on 
electrophoresis or  
• 
≥90% reduction in serum M-protein plus urine M-component level <100 mg/24 
h 
PR 
• 
≥50% reduction of serum M-protein plus reduction in 24 hours urinary M-
protein by ≥90% or to <200 mg/24 h 
• 
If the serum and urine M-protein are not measurable, a decrease ≥50% in the 
difference between involved and uninvolved FLC levels is required in place of 
the M-protein criteria. 
• 
If serum and urine M-protein are not measurable, and serum free light assay is 
also not measurable, ≥50% reduction in plasma cells is required in place of 
M-protein criteria, provided baseline bone marrow plasma cell percentage was 
≥30%. 
• 
In addition to the above listed criteria, if present at baseline, a ≥50% reduction 
in the size of soft tissue plasmacytomas4 is also required. 
MR 
• 
25% but 49% reduction of serum M protein and reduction in 24-hour urine M 
protein by 50% to 89% 
• 
In addition to the above criteria, if present at baseline, 50% reduction in the 
size of soft tissue plasmacytomas4 is also required. 
No increase in size or number of lytic bone lesions (development of compression 
fracture does not exclude response). 
SD 
Not recommended for use as an indicator of response; stability of disease is best 
described by providing the time-to-progression estimates. Not meeting criteria for CR, 
VGPR, PR, MR or PD 
PD2 
Any one or more of the following criteria:  
Increase of 25% from lowest confirmed response value in 1 or more of the following: 
• 
Serum M-protein (absolute increase must be 0.5g/dL); 
• 
Serum M-protein increase 1g/dL, if the lowest M-component was 5g/dL; 
• 
Urine M-protein (absolute increase must be 200 mg/24 h;  
• 
In participants without measurable serum and urine M-protein levels, the 
difference; between involved and uninvolved FLC levels (absolute increase 
must be >10 mg/dL); 
• 
In participants without measurable serum and urine M-protein levels and 
without measurable disease by FLC levels, bone marrow plasma cell absolute 
percentage of baseline status (absolute increase must be 10%). 
• 
Appearance of new lesion(s), 50% increase from nadir in SPD of >1 lesion, or 
50% increase in longest diameter of a previous lesion >1 cm in short axis. 
• 
≥50% increase in circulating plasma cells (minimum 200 cells per µL) if this is 
the only measure of disease. 


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CBR = clinical benefit rate; CR = complete response; FLC = free light chain; IMWG = International Myeloma Working 
Group; MR = minimal response; ORR = Objective response rate; PD = progressive disease; PR = partial 
response; sCR = stringent complete response; SD = stable disease; SPD=sum of the products of the maximal 
perpendicular diameters of measured lesions; VGPR = very good partial response.  
Objective Response Rate: Participants achieving sCR, CR, VGPR, and PR. 
Clinical Benefit Rate: Participants achieving sCR, CR, VGPR, PR, and MR. 
1.
All response categories require two consecutive assessments made any time before starting any new therapy 
2.
Clarifications to IMWG criteria for PD: Bone marrow criteria for PD are used only in participants without 
measurable disease by M protein and by FLC levels; “25% increase” refers to M protein, FLC, and bone 
marrow results but does not refer to bone lesions or soft tissue plasmacytomas; also, the “lowest response 
values” do not need to be a confirmed value.  
3.
Clarifications to IMWG criteria for coding CR and VGPR in participants in whom the only measurable disease is by 
serum FLC levels: CR in such participants is a normal FLC ratio of 0.26 to 1.65 in addition to CR criteria 
listed above. VGPR in such participants requires a >90% decrease in the difference between involved and 
uninvolved FLC levels. 
4.
Plasmacytoma measurements should be taken from the CT portion of the PET/CT, or MRI scans, or dedicated CT 
scans where applicable. For participants with only skin involvement, skin lesions should be measured with a 
ruler. Measurement of tumour size will be determined by the SPD. 
Notes:  
x
All category responses require no known evidence of progressive or new bone lesions if radiographic studies 
were performed.  
x
VGPR and CR categories require serum and urine studies regardless of whether disease at baseline was 
measurable on serum, urine, both, or neither. 
CCI


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Reference  
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET et al,. Toxicity and response criteria of the 
Eastern Cooperative Oncology Group. American journal of clinical oncology. 1982 Dec 1;5(6):649-56. 

CCI - This section contained Clinical Outcome Assessment data collection questionnaires or 
indices, which are protected by third party copyright laws and therefore have been excluded.


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11.8. 
Appendix 8: Modified Diet in Renal Disease (MDRD) Formula 
The MDRD formula for calculating the estimated glomerular filtration rate (eGFR) is as 
follows: 
eGFR = 175 × (Scr) -1.154 × (Age) -0.203 × (0.742 if female) × (1.212 if African American) 
GFR is expressed in mL/min/1.73 m2, SCr is serum creatinine expressed in mg/dL, and 
age is expressed in years.  
The link below will auto-calculate the creatinine clearance: http://nephron.org/cgi-
bin/MDRD_GFR/cgi  
 


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11.9. 
Appendix 9: Eye Care Specialist’s Qualifications and 
Requirements 
For examiners with a degree in optometry or ophthalmology, those involved in eye 
evaluations in the protocol must be able to provide comprehensive eye care to patients, 
ranging from routine check-ups to treatment and ongoing management of visual disease. 
This includes, as a minimum, the ability to perform the following activities:  
• Comprehensive eye exams  
• Visual acuity with manual refraction tests and analysis of results 
• Slit lamp tests and analysis of results  
• Intraocular pressure examination 
• Dilated fundoscopic examination 
• Diagnosis and treatment of ocular issues and diseases such as keratopathy or 
glaucoma 
• Communication with patients on the effect of belantamab mafodotin on the eye 
 


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11.10. 
Appendix 10: 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 
ASCT 
Autologous stem cell transplantation  
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 
BIB 
Bioanalysis Immunogenicity and Biomarkers 
BM 
Bone marrow 
BNP 
B-type natriuretic peptide 
BP 
Blood Pressure 
BUN 
Blood urea nitrogen 
C1D1 
Cycle 1 Day 1 
CBR 
Clinical Benefit Rate 
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 
Creatinine phosphokinase 
CR 
Complete response 
CRF 
Case Report Form 
CRP 
C-reactive protein 
CSR 
Clinical study report 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
Coefficient of variation 
DAMPs 
Danger-associated molecular patterns 
DCs 
Dendritic cells 
DEC 
Dose Escalation Committee 


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DICOM 
Digital Imaging and Communications in Medicine 
DILI 
Drug-induced liver injury 
DLT 
Dose limiting toxicities 
DMC 
Data Monitoring Committee 
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 
EOT 
End of treatment 
FISH 
Fluorescence in situ hybridization 
FLC 
Free light chain 
FSH 
Follicle stimulating hormone 
FTIH 
First Time in Human  
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GGT 
Gamma glutamyl transferase 
GSK 
GlaxoSmithKline 
HBV 
Hepatitis B virus 
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 
IB 
Investigator Brochure 
ICD 
Immunogenic cell death 
ICH 
International Conference on Harmonization 
IEC 
Independent Ethics Committee 
IgA 
Immunoglobulin A 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IMWG 
International Myeloma Working Group 
IP 
Investigational product 
IRB 
Institutional review board 
IRR 
Infusion related reaction 
IUD 
Intra-uterine device 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous 
LC 
Light chain  
LDH 
Lactate dehydrogenase 
LLN 
Lower limit of normal (range) 
LVEF 
Left ventricular ejection fraction 


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TLS  
Tumor Lysis syndrome  
Tmax 
Time of maximum observed concentration 
TNF 
Tumor necrosis factor 
UK 
United Kingdom 
ULN 
Upper limit of normal 
UPEP 
Urine protein electrophoresis 
US 
United States 
USP 
United States Pharmacopeia 
V 
Volume of distribution 
VGPR 
Very good partial response 
WBC 
White blood cell 
WFI 
Sterile water for injection 
WOCBP 
Woman of Childbearing Potential  
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
NONE 
 
MedDRA 
 
WinNonlin  


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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 2: 30-OCT-2020 
Overall Rationale for the Amendment: Per current available safety and efficacy 
information of belantamab mafodotin studies, the 3.4 mg/kg dose cohort is converted to 
an optional cohort in the dose-escalation study design. It may be determined not to 
escalate to based on clinical data from other belantamab mafodotin studies. 
Section # and 
Name 
Description of Change 
Brief Rationale 
Section 2.1 
As updated clinical experience 
language for studies BMA117159 and 
205678 has been added to Section 
2.2, the related information has been 
deleted from Section 2.1 
Updated relevant clinical data available 
and included in Section 2.2. 
Section 2.2 
Updated clinical experience language 
for studies BMA117159 and 205678 
Updated relevant clinical data available. 
Section 2.3 
Benefit/Risk 
Assessment  
Risk assessment details have been 
updated based on the updated safety 
profile. 
Program level update. 
Section 1.1, 
Synopsis, 
Section 1.2 
Schema, 
Section 2.3.2 
Benefit 
Assessment, 
Section 4.1.1 
Planned Dose 
Levels, 
Section 9.5.2 Dose 
Escalation 
Committee (DEC) 
A sentence has been added to reflect 
that 3.4 mg/kg dose may not be used 
in the study. 
Per current available safety and efficacy 
information of belantamab mafodotin 
studies, the 3.4 mg/kg dose cohort is 
converted to an optional cohort in the 
dose-escalation study design. It may be 
determined not to escalate to based on 
clinical data from other belantamab 
mafodotin studies. 
Section 1.1 
Synopsis, Section 
9.2 Sample Size 
Determination 
Up to six evaluable participants for 
each dose level. 
To clarify the sample size by dose levels 
since 3.4 mg/kg dose level is an optional 
cohort in the study design. 
Section 1.3 
Schedule of 
activities (SoA) 
Section 6.6.1 
Corneal Supportive 
Care Guideline for 
Belantamab 
Mafodotin 
Modification for ophthalmic exam 
information 
Program level update. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 6.5.2 
Prohibited 
Medication(s) 
Information related to use of vaccine 
has been updated. 
To enhance participants’ safety, the 
period for prohibited medication use of 
live/live-attenuated vaccines has been 
extended 
Section 6.5.3 
Prohibited 
Device(s) 
Information related to the use of 
contact lens has been updated. 
Program level update. 
Section 8 
Information related to imaging has 
been updated. 
For better clarity of the participants who 
need imaging . 
Section 8.1 
Efficacy 
Assessment 
Sentence added that the serum and 
urine immunofixation will be performed 
at the time of first achieving CR or 
suspected PD after CR or sCR 
For better clarity and consistency with 
SoA Table 
Section 7.1.1 Liver 
Chemistry Stopping 
Criteria 
Information of stopping criteria has 
been modified  
Availability of updated standard 
language for protocols 
Section 9.4.10 
Pharmacokinetic 
Analysis 
Additional AUC values added to 
parameter lists 
To add parameters calculated in other 
studies to support comparisons 
Appendix 5: Liver 
Safety: Required 
Actions and Follow-
up Assessments 
and Study 
treatment 
Rechallenge 
Guidelines 
Information of liver safety criteria has 
been modified  
Availability of updated standard 
language for protocols 
Appendix 9 Eye 
Care Specalist’s 
Qualification and 
Requirements 
Added Appendix 9: Eye Care 
Specialist’s Qualifications and 
Requirements.  
Program level update. 
Section 10 
References 
New references were added and 
references were updated 
Addition and update of references was 
done in parallel to changes in the main 
text. 
Throughout the 
protocol 
Changed the use of "subject", in the 
protocol to use "participant" only. 
Clarification of wording 
Whole document 
Minor editorial and document 
formatting revisions 
Minor, therefore have not been 
summarized 
 
Amendment 1: 02-Nov-2019 
Overall Rationale for the Amendment: The Centre of Drug Evaluation (CDE) China 
has recommended that the study participants should be sequentially entered into the 2.5 
mg/kg dose group to observe participants’ tolerance completely and collect PK data, 
based on tolerability results, the subsequent dosing plan should be adjusted as 
appropriate. The safety monitoring and risk management were enhanced based on the 
available data about the product. Ocular examination details were updated as CDE 
suggested to pay attention to corneal examination and collection of patient-reported 


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symptoms during the clinical study based on the occurrence of corneal toxicity of this 
product. The pregnancy data collection and contraception period were revised as toxic 
effects on the fertility could be observed in repeat dose toxicity studies.  
Section # and 
Name 
Description of Change 
Brief Rationale 
Section 4.1.1. 
Planned Dose 
Levels 
The first 3 participants in 2.5 mg/kg 
dose group will receive the study 
treatment sequentially with an 
observation window of 7 days, to 
observe acute toxicities. If the 
participating investigator and the 
coordinating investigator see no 
potential safety concerns from the 
first participant, the participating 
investigator and the coordinating 
investigator may recommend to 
enroll the next participant. If 1 or 
more participants experience a 
DLT, dose will be de-escalated to 
1.9 mg/kg if the current dose cohort 
is 2.5 mg/kg. 
To ensure adequate safety 
observation and data collection, prior 
to adding the next patient at the 
same dose level, based on tolerability 
results. Subsequent dosing plan can 
be adjusted as appropriate. 
Section 1.1 
Synopsis, Section 
1.3. Schedule of 
Activities (SoA), 
Section 3 
Objectives and 
Endpoints, 8.2.7. 
Visual Function 
Questionnaire 
Collection of participant self-
reported symptoms using the OSDI 
has been added. 
Collection of participant self-reported 
symptoms during the clinical study 
based on the occurrence of corneal 
toxicity of this product 
Section 2.3.1. 
Risk Assessment 
Risk assessment details have been 
updated with two new risks 
(embryo-fetal toxicity and impaired 
male fertility) added and the risk of 
‘Potential for overdose specific to 
the preparation of study drug’ 
removed. Changes on corneal 
examination, infusion related 
reaction, neutropenia, potential for 
cardiotoxicity related to an 
inflammatory response, 
hepatotoxicity, nephrotoxicity, and 
potential for other laboratory 
abnormalities were updated. 
Based on the updated safety profile, 
use of belantamab mafodotin in 
pregnant women may cause fetal 
harm and in animal studies, 
belantamab mafodotin treatment has 
resulted in testicular toxicity and 
adverse effects on spermatogenesis. 
GSK does not recommend a specific 
treatment for an overdose as there is 
no specific antidote for the overdose 
of belantamab mafodotin. For the 
treatment of overdose can reach out 
to Section 8.4. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 6.6. Dose 
Modification 
Dose modification guidelines were 
updated for thrombocytopenia, 
febrile neutropenia and added for 
neutropenia 
More details are added in this section 
based on the latest available 
information. 
Section 7.  
Update the wording in the section 
of discontinuation of study 
treatment and participant 
discontinuation/withdraw 
Discontinuation section has been 
updated based on the information 
from the ongoing clinical programme. 
Section 1.1 
Synopsis, Section 
5.1 Inclusion 
Criteria 
Contraception period has been 
extended 
The study drug has not been 
evaluated for reproductive toxicity in 
any of the clinical studies. To protect 
participants from fetal toxicity, 
pregnancy should be avoided for an 
extended period. 
Section 1.3 
Schedule of 
Activities (SoA), 
Section 8.3.5. 
Pregnancy, 
Section 11.4. 
Appendix 4: 
Contraceptive 
Guidance and 
Collection of 
Pregnancy 
Information 
Pregnancy data collection periods 
have been extended and final 
pregnancy test time point has been 
changed, 
To collect additional data to further 
define the safety profile of 
belantamab mafodotin in relation to 
fetal toxicity. 
Section 8.3.9. 
Ocular Subset 
Examinations  
Ocular exam details have been 
updated 
Updated with latest procedure. 
Section 1.3. 
Schedule of 
Activities (SoA), 
Section 2.3.1 
Risk Assessment, 
Section 6.6 Dose 
Modification, 
Section 6.6.1 
Corneal 
Supportive Care 
Guidelines for 
Steroid eye drops administered as 
prophylaxis is no longer mandated 
but can be used if clinically 
indicated at the discretion of an 
eye-care specialist 
Update to the wording on frequency 
of ophthalmologic assessments 
New dose modification guidance 
(based on CTCAE 5.0) 
Based on the data from the ongoing 
clinical programme: 
• Steroid eye drops were not found 
to provide benefit to participants. 
• It has been determined that 
participant symptoms should 
determine the need for 
ophthalmology exams 
The need for dose delay/reduction 
should be determined by participant 


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Section # and 
Name 
Description of Change 
Brief Rationale 
belantamab 
mafodotin 
symptoms (not asymptomatic corneal 
changes) 
Section 9.5.2. 
Dose Escalation 
Committee 
Dose Escalation Committee (DEC) 
details have been added 
The DEC will monitor intervention-
emergent data on an ongoing basis 
throughout study conduct for the 
purpose of ensuring the continued 
safety of participants enrolled in this 
study as described in the Dose 
Escalation Plan. 
Previous Section 
11.1.5. 
Committees 
Structure 
Deleted this section which provided 
information on the Independent 
review committee (IRC) 
IRC is not required for phase 1 
studies, since efficacy is not a 
primary endpoint and can be 
adequately assessed by 
investigators. 
Section 11.2. 
Appendix 2: 
Clinical 
Laboratory Tests 
Removed the wording related to 
results to be stored by third party 
Results will be stored at sites 
Previous Section 
11.8. Appendix 8: 
Corneal Event 
Severity Grading 
and Mitigation 
Strategy 
Deleted the Appendix 
Information on corneal event severity 
grading and mitigation strategy is 
already included under Section 6.6. 
Dose Modification and Section 6.6.1 
Corneal Supportive Care Guidelines 
for Belantamab Mafodotin 
Section 10 
References 
New references were added and 
references were updated 
Addition and update of references 
were because of changes in the main 
text. 
All Sections 
Replaced “GSK2857916” with 
“Belantamab Mafodotin” throughout 
the document 
Updated with generic name 
Minor typographical errors were corrected in the document 
 

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CCI


 
CONFIDENTIAL 
 
208465 
 
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8.8.2. 
ECG ............................................................................................. 23 
9. 
IMMUNOGENICITY / BIOMARKER ANALYSES .................................................... 24 
10. PHARMACOKINETIC ANALYSES ......................................................................... 25 
10.1. 
Drug Concentration Measures .................................................................... 25 
10.1.1. 
Non-compartmental Analysis ....................................................... 25 
10.2. 
Population of Interest .................................................................................. 26 
10.3. 
Statistical Analyses / Methods .................................................................... 26 
10.3.1. 
Statistical Methodology Specification ........................................... 26 
11. PHARMACOKINETIC / PHARMACODYNAMIC ANALYSES ................................. 28 
11.1. 
Exposure-Response for Efficacy and Safety Endpoints .............................. 28 
11.2. 
Concentration-QTc Analyses ...................................................................... 28 
12. PHARMACODYNAMIC AND BIOMARKER ANALYSES ........................................ 29 
13. REFERENCES ....................................................................................................... 30 
14. APPENDICES ........................................................................................................ 31 
14.1. 
Appendix 1: Exclusions from Per Protocol Population ................................. 31 
14.2. 
Appendix 2: Schedule of Activities .............................................................. 32 
14.3. 
Appendix 3: Assessment Windows ............................................................. 36 
14.4. 
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................ 37 
14.4.1. 
Study Phases .............................................................................. 37 
14.4.2. 
Treatment Emergent Flag for Adverse Events ............................. 39 
14.5. 
Appendix 5: Data Display Standards & Handling Conventions .................... 40 
14.5.1. 
Reporting Process ....................................................................... 40 
14.5.2. 
Reporting Standards .................................................................... 40 
14.5.3. 
Reporting Standards for Pharmacokinetic .................................... 41 
14.6. 
Appendix 6: Derived and Transformed Data ............................................... 42 
14.6.1. 
General ........................................................................................ 42 
14.6.2. 
Study Population .......................................................................... 42 
14.6.3. 
Efficacy ........................................................................................ 42 
14.6.4. 
Safety .......................................................................................... 43 
14.6.5. 
Pharmacokinetic .......................................................................... 43 
14.7. 
Appendix 7: Reporting Standards for Missing Data ..................................... 44 
14.7.1. 
Premature Withdrawals ................................................................ 44 
14.7.2. 
Handling of Missing Data ............................................................. 44 
14.8. 
Appendix 8: Values of Potential Clinical Importance ................................... 47 
14.8.1. 
Laboratory Values ........................................................................ 47 
14.8.2. 
ECG Parameters and Vital Signs ................................................. 47 
14.9. 
Appendix 9: Pharmacokinetic / Pharmacodynamic Analyses ...................... 48 
14.9.1. 
Pharmacokinetic / Pharmacodynamic Dataset 
Specification ................................................................................ 48 
14.9.2. 
Pharmacokinetic / Pharmacodynamic Methodology ..................... 48 
14.10. Appendix 10: Pharmacodynamic Biomarkers and Exploratory 
Response Prediction Biomarkers ................................................................ 49 
14.10.1. Pharmacodynamic Biomarkers and Exploratory Response 
Prediction Biomarkers Dataset Specification ................................ 49 


 
CONFIDENTIAL 
 
208465 
 
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14.10.2. Pharmacodynamic Biomarkers and Exploratory Response 
Prediction Biomarkers Methodology............................................. 49 
14.11. Appendix 11: Abbreviations & Trade Marks ................................................ 50 
14.11.1. Abbreviations ............................................................................... 50 
14.11.2. Trademarks ................................................................................. 52 
14.12. Appendix 12: List of Data Displays.............................................................. 53 
14.12.1. Data Display Numbering .............................................................. 53 
14.12.2. Mock Example Shell Referencing ................................................ 53 
14.12.3. Deliverables ................................................................................. 53 
14.12.4. Study Population Tables .............................................................. 54 
14.12.5. Study Population Figures ............................................................. 56 
14.12.6. Efficacy Tables ............................................................................ 57 
14.12.7. Efficacy Figures ........................................................................... 58 
14.12.8. Dose Limiting Toxicity Tables ...................................................... 59 
14.12.9. Dose Limiting Toxicity Figures ..................................................... 60 
14.12.10. Safety Tables ............................................................................... 61 
14.12.11. Safety Figures ............................................................................. 63 
14.12.12. Immunogenicity/Biomarker Tables ............................................... 64 
14.12.13. Immunogenicity Figures ............................................................... 65 
14.12.14. Pharmacokinetic Tables ............................................................... 66 
14.12.15. Pharmacokinetic Figures ............................................................. 67 
14.12.16. Pharmacokinetic / Pharmacodynamic Tables .............................. 68 
14.12.17. Pharmacokinetic / Pharmacodynamic Figures ............................. 69 
14.12.18. Pharmacodynamic Biomarkers and Exploratory Response 
Prediction Biomarkers Tables ...................................................... 70 
14.12.19. Pharmacodynamic Biomarkers and Exploratory Response 
Prediction Biomarkers Figures ..................................................... 71 
14.12.20. ICH Listings ................................................................................. 72 
14.12.21. Non-ICH Listings .......................................................................... 75 
14.13. Appendix 13: Example Mock Shells for Data Displays ................................ 77 
 


 
CONFIDENTIAL 
 
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1. 
INTRODUCTION 
The purpose of this reporting and analysis plan (RAP) is to describe the planned analyses 
to be included in the CSR for Protocol 208465/Amendment 3: 
Revision Chronology: 
Original Protocol 
01-Apr-2019 
Original 
Amendment 1 
02-Nov-2019 
The Centre of Drug Evaluation (CDE) China has 
recommended that the study participants should be 
sequentially entered into the 2.5 mg/kg dose group to observe 
participants’ tolerance completely and collect PK data, based 
on tolerability results, the subsequent dosing plan should be 
adjusted as appropriate. The safety monitoring and risk 
management were enhanced based on the available data 
about the product. Ocular examination details were updated 
as CDE suggested to pay attention to corneal examination 
and collection of patient-reported symptoms during the 
clinical study based on the occurrence of corneal toxicity of 
this product. The pregnancy data collection and contraception 
period were revised as toxic effects on the fertility could be 
observed in repeat dose toxicity studies 
Amendment 2 
30-Oct-2020 
Per current available safety and efficacy information of 
belantamab mafodotin studies, the 3.4 mg/kg dose cohort is 
converted to an optional cohort in the dose-escalation study 
design. It may be determined not to escalate to based on 
clinical data from other belantamab mafodotin studies. 
Amendment 3 
26-Oct-2021 
The protocol has been amended to accommodate the 
updates based on latest information available through 
investigator’s brochure. The study period was extended to 
maintain the study treatment of two ongoing participants who 
are benefitting from the Belantamab mafodotin treatment as 
judged by investigator. 
 
 
 
 


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Objectives 
Endpoints 
Primary 
Primary  
x
To determine safety and 
tolerability of belantamab 
mafodotin in Chinese Participants 
with RRMM 
x
Adverse events (AE), i.e., number (%) of participants with 
DLTs, number (%) of participants with AEs 
Secondary 
Secondary  
x
To evaluate PK profile of 
belantamab mafodotin in Chinese 
Participants with RRMM 
x
ADC, total antibody and cys-mcMMAF PK parameters 
following IV single and repeat dose administration during 
dose escalation as data permit (e.g., AUC, Cmax, tmax) 
x
To evaluate safety and tolerability 
of belantamab mafodotin 
x
Changes in clinical signs and laboratory parameters, 
ocular findings on ophthalmic exam 
x
To evaluate the clinical measures 
of efficacy of belantamab 
mafodotin  
x
ORR, defined as the percentage of participants with a 
confirmed partial response (PR) or better (i.e., VGPR, CR 
and stringent complete response [sCR]), according to the 
International Myeloma Working Group (IMWG) Response 
Criteria. 
x
To assess anti-drug antibody 
(ADA) formation after IV single 
and repeat dose administration of 
belantamab mafodotin 
x
Incidence and titers of ADAs against belantamab 
mafodotin 
x
Participant self-reported 
symptomatic adverse effects by 
evaluation of tolerability of 
belantamab mafodotin 
x
Symptomatic adverse effects and related impacts as 
measured by the OSDI 
Exploratory 
Exploratory 
Abbreviations: IV = intravenous; BCMA = B-cell maturation antigen; MMAF = monomethyl auristatin-F; ORR = overall 
response rate; CR = complete response; DLT=dose-limiting toxicity; VGPR = very good partial response; PR = partial 
response; sCR = Stringent complete response; PK = pharmacokinetics; AUC = area under the curve; Cmax = maximum 
concentration; Tmax = time to maximum; ADA = anti-drug antibody; OSDI = Ocular Surface Disease Index; 
 


CCI
CCI
CCI


 
CONFIDENTIAL 
 
208465 
 
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2.3. 
Study Design 
Overview of Study Design and Key Features 
  
Note: De-escalation to 1.9 mg/kg will be allowed in case of ≥2 DLT at dose 2.5 mg/kg 
As per current available safety and efficacy information of belantamab mafodotin studies, the 3.4 mg/kg dose cohort 
is converted to an optional cohort in the dose-escalation study design. Escalation may not proceed if not supported 
by emerging clinical data from other belantamab mafodotin studies. 
Design 
Features 
• 
Phase I, open-label dose-escalation study to explore safety, PK, tolerability, 
immunogenicity and clinical activity of belantamab mafodotin monotherapy in 
Chinese participants with RRMM. The study will enroll up to 12 evaluable 
participants. This study will include two dose cohorts. Up to six evaluable 
participants are expected for each cohort and the actual numbers will depend on 
the safety observed. Each participant will be involved in the study until participant 
have progressed, died, withdrawn consent, discontinued treatment due to other 
reasons, or have been lost to follow-up. 
• 
Based on the 3+3 dose escalation design the anticipated size will be up to 6 
evaluable participants for each dose level. 
Dosing 
• 
Belantamab mafodotin will be administered via 30-60 min intravenous (IV) 
infusion once every three weeks (21 days = 1 cycle). 
Time 
& 
Events 
• 
Refer to Appendix 2: Schedule of Activities 
Treatment 
Assignment 
• 
Projected dose levels are 2.5 mg/kg and 3.4 mg/kg. De-escalation to 1.9 mg/kg will 
be allowed in case of ≥2 DLT at dose 2.5 mg/kg. The first 3 participants in 2.5 
mg/kg dose group will receive the study treatment sequentially with an observation 
window of 7 days, to observe acute toxicities. 
Interim 
Analysis 
• 
No interim analysis is planned. 
 


 
CONFIDENTIAL 
 
208465 
 
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2.4. 
Statistical Hypotheses / Statistical Analyses 
Due to limited sample size and the purpose of the study, no formal statistical hypotheses 
are being tested. Primary objective of the study is to determine safety and tolerability of 
belantamab mafodotin in Chinese Participants with RRMM. Analysis of the data will only 
utilise descriptive methods. 


 
CONFIDENTIAL 
 
208465 
 
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3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
No interim analysis is planned in this study. 
3.2. 
Final Analyses 
The final planned primary analyses will be performed after the completion of the following 
sequential steps: 
1. All participants have completed the study as defined in the protocol, i.e., when all 
participants have progressed, died, withdrawn consent, discontinued treatment due 
to other reasons, or have been lost to follow-up. 
2. All required database cleaning activities have been completed and final database 
release (DBR) and database freeze (DBF) has been declared by Data Management. 
 
 


 
CONFIDENTIAL 
 
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4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
Screened  
• 
All participants who were screened for eligibility 
• 
Study 
Population 
Enrolled 
• 
All participants who passed screening and entered the 
study. 
• 
Note screening failures (who never passed screening 
even if rescreened) and participants screened but never 
enrolled into the study (Reserve, Not Used) are excluded 
from the Enrolled population as they did not enter the 
study. 
• 
Study 
Population 
All Treated 
 
• 
All eligible participants who receive at least 1 dose of 
study treatment. An incorrect treatment schedule or drug 
administration or an early termination of treatment will not 
result in exclusion of participants from this population. 
• 
Study 
Population 
• 
Safety 
(except 
the 
DLT 
analysis) 
• 
Efficacy 
DLT Evaluable 
• 
All the eligible participants who have received the 1st 
dose as planned, and experienced a DLT during the cycle 
1 or completed the cycle 1. Participants who have been 
replaced during cycle 1 will be excluded from the DLT 
evaluable population. 
• 
Summary 
of 
DLT 
Pharmacokinetic 
(PK) 
• 
All participants in the “All Treated” population from whom 
at least one PK sample was obtained, analyzed, and was 
measurable. 
• 
PK 
Refer to Appendix 12: List of Data Displays which details the population used for each display. 
 


 
CONFIDENTIAL 
 
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4.1. 
Protocol Deviations 
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be summarised 
and listed. 
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan (PDMP) 4.0_04Jun2021. 
o Data will be reviewed prior to freezing the database to ensure all important 
deviations are captured and categorised on the protocol deviations dataset.  
o This dataset will be the basis for the summaries and listings of protocol deviations. 
A listing of all inclusion/exclusion criteria deviations will also be provided.  


 
CONFIDENTIAL 
 
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5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
5.1. 
Study Treatment & Sub-group Display Descriptors 
There are no treatment comparisons. Analysis of the data obtained will only utilise 
descriptive methods. 
5.2. 
Baseline Definitions 
For all endpoints (except as noted in baseline definitions) the baseline value will be the 
latest pre-dose assessment with a non-missing value, including those from unscheduled 
visits. If time is not collected, Day 1 assessments are assumed to be taken prior to first dose 
and used as baseline. For ECG analyses, participant level baseline is defined as the mean 
of triplicate baseline assessments. 
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing. 
Definition 
Reporting Details 
Change from Baseline 
= Post-baseline Value – Baseline 
% Change from Baseline 
= 100 x [(Post-baseline Value – Baseline) / Baseline] 
 
5.3. 
Other Considerations for Data Analyses and Data Handling 
Conventions 
Other considerations for data analyses and data handling conventions are outlined in the 
appendices: 
Section 
Component 
Section 14.3 
Appendix 3: Assessment Windows 
Section 14.4 
Appendix 4: Study Phases and Treatment Emergent Adverse Events 
Section 14.5 
Appendix 5: Data Display Standards & Handling Conventions 
Section 14.6 
Appendix 6: Derived and Transformed Data 
Section 14.7 
Appendix 7: Reporting Standards for Missing Data 
Section 14.8 
Appendix 8: Values of Potential Clinical Importance 
 


 
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6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Study Population Analyses 
The study population analyses will be based on the “All Treated” population, unless 
otherwise specified. The summary of screening failures and reasons for screening failure 
will be based on the “Screened” population, unless otherwise specified. 
Study population analyses including analyses of participant’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications 
will be based on GSK Core Data Standards. Details of the planned displays are presented 
in Appendix 12: List of Data Displays. 
6.2. 
Participant’s Disposition 
A summary of the number of participants in each of the analysis populations described in 
Section 4 will be provided using “Screened” population.  
A summary of participant status and reason for study withdrawal will be provided. This 
display will show the number and percentage of participants who withdrew from the study, 
including the primary reasons for study withdrawal. Reasons for study withdrawal will be 
presented in the order they are displayed in the eCRF. 
A summary of study treatment status will be provided. This display will show the number 
and percentage of participants who are ongoing or discontinued study treatment and a 
summary of the primary reasons for discontinuation of study treatment. Reasons for study 
treatment discontinuation will be presented in the order they are displayed in the eCRF. A 
listing of study treatment discontinuation will be generated. The listing will include last 
dose date, and reasons for study treatment discontinuation. 
6.3. 
Demographic and Baseline Characteristics  
The demographic characteristics (e.g., age, race, ethnicity, sex, baseline height, baseline 
body weight, and baseline BMI) will be summarized and listed. Age, height, weight and 
BMI will be summarized using mean, standard deviation, median, minimum, and 
maximum. The count and percentage will be computed for sex and ethnicity. 
Disease history and characteristics (e.g. time since initial diagnosis in years, stage at initial 
diagnosis, date of initial diagnosis) at initial diagnosis and screening will be listed. 
Summaries of disease characteristics at initial diagnosis and screening will be provided. 
Disease characteristics at screening, including stage, type of multiple myeloma, myeloma 
light chain, and immunoglobulin, and whether or not have extramedullary disease and lytic 
bone lesions will be summarized and listed. 
Genetic characteristics and Cytogenetic risk for multiple myeloma participants at screening 
will be summarized. Genetic characteristics will be listed. A participant is considered as 
having high cytogenetic risk if the participant has any of the following cytogenetics: 
t(4;14), del17p, t(14;16). 


 
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Current medical conditions, such as liver disease medical conditions, cardiovascular risk 
factors and other medical conditions will be summarized and will be sorted by decreasing 
overall frequency. A by-participant listing of medical conditions will also be provided. 
Prior anti-cancer therapy will be listed.  
Prior anti-cancer therapy for multiple myeloma participants will also be summarized by 
type of therapy, and drug class. A summary of multiple myeloma participants’ refractory 
to prior anti-cancer therapy by drug class will be provided. 
6.4. 
Treatment Compliance 
Summaries of study treatment exposure and dose modifications (e.g., number of dose 
reductions, number of dose delays) will further characterize compliance. These analyses 
are described in Section 6.5 ‘Extent of Exposure’. 
6.5. 
Extent of Exposure 
Extent of exposure to Belantamab Mafodotin will be summarized. 
The number of cycles administered to study treatment will be summarised with mean, 
median, standard deviation, minimum, and maximum. The number and percentage of 
participants who received a given number of cycles (<4, 4, and >4 cycles) will be reported. 
The duration of exposure to study treatment in days (from first day to last day of treatment) 
will be calculated and summarized using mean, median, standard deviation, minimum, and 
maximum. A horizontal bar graph of duration of treatment will be produced that displays 
duration of treatment in months for each participant. 
A by participant summary listing of data on exposure to all study treatments will be 
produced. 
Dose reductions will be summarised by number of reductions and reasons for reductions.  
Dose delays will be summarised by number of delays, reasons for the delays, and delay 
duration (days). The number and percentage of the delays for intervals of 1-21, 22-42 and 
>42 days will be computed.  
Duration of delays is defined as period from the expected start date of dose to actual start 
date of current dose. Calculation: (actual start date of current dose - expected start date of 
dose). Expected start date of dose = actual start date of previous dose + 21. 
The summaries of dose modifications will be provided. All the dose reductions and dose 
delays will be listed. 
6.6. 
Concomitant Medications 
Concomitant medications will be coded using GSK Drug coding dictionary, summarized, 
and listed. The summary of concomitant medications will show the number and percentage 
of participants taking concomitant medications by Ingredient. Multi-ingredient products 
will be summarized by their separate ingredients rather than as a combination of 
ingredients. Anatomical Therapeutic Chemical (ATC) classification Level 1 (Body 


 
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System) information will be included in the dataset created but will not appear on the listing 
or summary. 
In the summary of concomitant medications, each participant is counted once within each 
unique ingredient. For example, if a participant takes Amoxycillin on two separate 
occasions, the participant is counted only once under the ingredient “Amoxycillin”. In the 
summary of concomitant medications, the ingredients will be summarized by the base only, 
using CMBASECD and CMBASE. Note: In order to be considered a concomitant 
medication, the concomitant medication must have been taken at some point during the on-
treatment window. 
Blood products or blood supportive care products with onset date within the on-therapy 
window will be included in the summary tables. The frequency and percentage of subjects 
using blood products and blood supportive care products after the start of study medication 
will be provided. Supporting listings will also be provided. 
 


 
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7. 
EFFICACY ANALYSES 
The efficacy analyses will be based on the All Treated population, unless otherwise 
specified. 
Details of the planned displays are provided in Appendix 12: List of Data Displays and 
will be based on GSK data standards and statistical principles. 
Unless otherwise specified, the following endpoints / variables will be summarised using 
descriptive statistics, graphically presented (where appropriate) and listed. 
7.1. 
Objective response rate (ORR) 
ORR is defined as the percentage of participants with a confirmed partial response (PR) or 
better (i.e., VGPR, CR and stringent complete response [sCR]) as assessed according to  
IMWG Uniform Response Criteria for Multiple Myeloma 2016 (See Protocol Appendix 6) 
by the Investigator.  
ORR and the associated 2-sided 95% exact confidence intervals will be provided. A list of 
investigator-assessed response at each visit will be listed. 
The following rule of confirmation will be used to confirm the response (i.e., PR, VGPR, 
CR and sCR): 
• PR: two consecutive response of PR or better at any time before starting any new 
therapy. 
• VGPR: two consecutive responses of VGPR or better at any time before starting 
any new therapy. 
• CR: two consecutive response of CR or better (i.e. sCR) at any time before 
starting any new therapy. 
• sCR: two consecutive responses of sCR at any time before starting any new 
therapy. 
7.1.1. 
Derivation of Confirmed Response  
The derivation of confirmed response shall be based on the algorithm specified in Table 1. 
The date of the first of the two consecutive assessments will be used as the date of the 
confirmed response. 
Table 1 
Response confirmation algorithm 
# 
Response at the First 
Time Point 
Response at Subsequent 
Disease Assessment1 
Confirmed Response at 
the First Time Point 
1 
sCR 
sCR 
sCR 
2 
sCR 
CR 
CR 
3 
CR 
sCR/CR 
4 
sCR/CR 
VGPR 
VGPR 
5 
VGPR 
sCR/CR/VGPR 
6 
sCR/CR/VGPR 
PR 
PR 
7 
PR 
sCR/CR/VGPR/PR 


 
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# 
Response at the First 
Time Point 
Response at Subsequent 
Disease Assessment1 
Confirmed Response at 
the First Time Point 
8 
sCR/CR/VGPR/PR 
MR 
MR 
9 
MR 
sCR/CR/VGPR/PR/MR 
10 
sCR/CR/VGPR/PR/MR 
SD 
SD 
11 
sCR/CR/VGPR/PR/MR 
PD (any reason) 
 
OR 
No subsequent disease 
assessment: subject died or 
discontinued study or 
started new anti-cancer 
therapy before further 
adequate disease assessment 
NE 
12 PD (due to reasons other 
than imaging, i.e., 
plasmacytoma or bone 
lesion) 
PD (any reason) including PD 
after initiation of new anti-
cancer therapy 
 
OR 
No subsequent disease 
assessment: subject died due 
to PD before further adequate 
disease assessment 
(including death due to PD 
after initiation of new anti-
cancer therapy) 
PD 
13 PD (due to reasons other 
than imaging, i.e., 
plasmacytoma or bone 
lesion) 
sCR/CR/VGPR/PR/MR/SD 
 
OR 
No subsequent disease 
assessment: subject died due 
to reasons other than PD 
before further adequate 
disease assessment 
 
OR 
No subsequent disease 
assessment: subject 
discontinued study before 
further adequate disease 
assessment 
NE 
14 sCR/CR/VGPR/PR/MR/PD 
(due to reasons other than 
imaging, i.e., plasmacytoma 
or bone lesion) 
No subsequent disease 
assessment: subject has not 
died, discontinued from study 
or (except for PD) started new 
anti-cancer therapy; but as yet 
has no further adequate 
disease assessments 
Unconfirmed 
sCR/CR/VGPR/PR/MR/PD. 
 
Will be categorized as NE 
for final ORR analysis. 
 
For ORR analysis in IA, the 
UC response (PR or better) 
will be counted as 
responder. 
15 SD 
Any 
SD 


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# 
Response at the First 
Time Point 
Response at Subsequent 
Disease Assessment1 
Confirmed Response at 
the First Time Point 
 
OR 
No subsequent disease 
assessment 
16 PD due to  
imaging (plasmacytoma or 
bone lesion) 
Any 
 
OR 
No subsequent disease 
assessment 
PD 
17 NE or missing 
Any 
 
OR 
No subsequent disease 
assessment 
NE 
1. Subsequent disease assessment is defined as the next adequate (not missing or NE) disease 
assessment following the first timepoint before (or on the same date of) start of new anti-cancer 
therapy except for confirmation of PD, for which PD or death due to PD after new anti-cancer 
therapy are considered for confirmation of PD. No minimal time interval is required for the 
subsequent disease assessment, but a different sample is required for confirmation. 
2. PD due to imaging (i.e., plasmacytoma or bone lesion) does not need to be confirmed. 
3. Where criteria are not mutually exclusive, take the first that applies. 

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8. 
SAFETY ANALYSES 
The primary endpoints are adverse events, i.e., the number (%) of participants with DLTs, 
and the number (%) of participants with AEs. 
The DLT analyses will be based on the DLT Evaluable population, unless otherwise 
specified. 
The safety analyses (except the DLT analysis) will be based on the All Treated population, 
unless otherwise specified. 
8.1. 
Dose Limiting Toxicity Analyses 
The DLTs is one of the primary endpoints, the number and proportion of participants in 
the DLT population who experienced DLT during the Cycle 1 of study treatment will be 
presented. Details of the planned displays are presented in Appendix 12: List of Data 
Displays. 
8.2. 
Adverse Events Analyses 
Adverse events analyses including the analysis of adverse events (AEs), serious adverse 
events (SAEs) and other significant AEs will be based on GSK Core Data Standards. The 
details of the planned displays are provided in Appendix 12: List of Data Displays. 
An overview summary of AEs, including counts and percentages of participants with any 
AE, AEs related to study treatment, Grade 3 or 4 AEs, Grade 3 or 4 AEs related to study 
treatment, AEs leading to permanent discontinuation of study treatment, AE leading to 
dose reductions, AEs leading to dose delays OR interruptions, SAEs, SAEs related to study 
treatment, fatal SAEs, and fatal SAEs related to study treatment will be produced. 
A summary of non-serious AEs will be provided. The summary will be displayed by PT. 
The relationship between PT and Verbatim Text will be displayed. 
Adverse events (AEs) will be coded using the standard Medical Dictionary for Regulatory 
Activities (MedDRA). Severity of corneal events will be graded using the scale provided 
in Table 7 of the Study Protocol. The severity of other AEs will be graded by the 
investigator according to the National Cancer Institute-Common Toxicity Criteria for 
Adverse Events (NCI-CTCAE) (version 5.0).  
A summary of number and percentage of participants with any adverse events by maximum 
grade will be produced. AEs will be sorted by Preferred term (PT) in descending order of 
total incidence. The summary will use the following algorithms for counting the 
participant: 
• 
Preferred term row: Participants experiencing the same AE preferred term several 
times with different grades will only be counted once with the maximum grade. 


 
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• 
Any event row: Each participant with at least one adverse event will be counted only 
once at the maximum grade no matter how many events they have. 
In addition, the frequency and percentage of AEs (all grades) will be summarized and 
displayed in descending order of total incidence by PT only.  
A separate summary will be provided for study treatment-related AEs. A study treatment-
related AE is defined as an AE for which the investigator classifies the relationship to study 
treatment as “Yes”. A worst-case scenario approach will be taken to handle missing 
relatedness data, i.e. the summary table will include events with the relationship to study 
treatment as ‘Yes’ or missing. The summary table will be displayed by maximum grade 
sorted by PT in descending order of total incidence.  
In addition, AEs of maximum grade of 3 or higher will be summarized separately by PT. 
All AEs will be listed. Additionally, a listing of participant IDs for each individual AE will 
be produced.  
The details of the planned displays are provided in Appendix 12: List of Data Displays. 
8.3. 
Adverse Events of Special Interest Analyses 
Adverse events of special interest (AESI) for belantamab mafodotin are corneal events, 
thrombocytopenia and infusion related reactions.  
Summaries of the number and percentage of participants with these events will be provided 
for each type of events separately by preferred term and maximum grade. The time of onset 
and duration of first occurrence of corneal events will be summarized using summary 
statistics mean, standard deviation, median, minimum value, and maximum. The number 
and percentage of participants who have time of onset of first occurrence (1-21, 22-42, 43-
63, >63 days) will be reported. The number and percentage of participants who have 
duration of first occurrence (1-21, 22-42, >42 days) will be reported. 
The summary of event characteristics of corneal events and thrombocytopenia will also be 
provided, including number of participants with any event, number of events, number of 
participants with any event that is serious, number of participants with any event that is 
related to study treatment, number of occurrences (One, Two, Three or more), maximum 
grade and the action taken for the event. The percentage will be calculated in two ways, 
one with number of participants with event as the denominator and the other with total 
number of participants as the denominator. The worst-case approach will be applied at 
participant level for the maximum grade, i.e. a participant will only be counted once as the 
worst case from all the events experienced by the participant. For action taken to an event, 
participant will be counted once under each action, e.g. if a participant has an event leading 
to both study treatment discontinuation and dose reduction, the participant will be counted 
once under both actions. 
A comprehensive list of MedDRA terms based on clinical review will be used to identify 
each type of event. The details of the planned displays are provided in Appendix 12: List 
of Data Displays. 


 
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8.4. 
Serious Adverse Events 
All SAEs will be tabulated based on the number and percentage of participants who 
experienced the event. Separate summaries will also be provided for study treatment-
related SAEs. The summary tables will be displayed in descending order by PT.  
A study treatment-related SAE is defined as an SAE for which the investigator classifies 
the relationship to study treatment as “Yes”. A worst-case scenario approach will be taken 
to handle missing data, i.e. the summary table will include events with the relationship to 
study treatment as ‘Yes’ or missing.  
8.5. 
SAEs are included in the listing of all adverse events. 
Adverse Events Leading to Discontinuation of Study 
Treatment and Dose Modification 
The following categories of AEs will be summarized by PT and separate supportive listings 
will be generated with participant level details for those participants: 
• 
AEs Leading to Permanent Discontinuation of Study Treatment  
• 
AEs Leading to Dose Interruptions or Delays 
• 
AEs Leadings to Dose Reductions 
8.6. 
Pregnancies  
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 recorded as an AE or 
SAE as described in the protocol. If participants and participants’ partner become pregnant 
while on the study, the information will be included in the narratives and no separate table 
or listing will be produced. 
8.7. 
Clinical Laboratory Analyses 
Only local laboratory evaluations including the analyses of Chemistry laboratory tests, 
Haematology laboratory tests, Urinalysis, and liver function tests will be based on GSK 
Core Data Standards. The details of the planned displays are in Appendix 12: List of Data 
Displays.  
Summaries of worst case grade increase from baseline grade will be provided for all the 
lab tests that are gradable by CTCAE v5.0. These summaries will display the number and 
percentage of participants with a maximum post-baseline grade increasing from their 
baseline grade. Any increase in grade from baseline will be summarized along with any 
increase to a maximum grade of 3 and any increase to a maximum grade of 4. Missing 
baseline grade will be assumed as grade 0. For laboratory tests that are graded for both low 
and high values, summaries will be done separately and labelled by direction, e.g., sodium 
will be summarized as hyponatremia and hypernatremia. 


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9. 
IMMUNOGENICITY / BIOMARKER ANALYSES 
For each participant, the anti-belantamab mafodotin (drug) antibody results, titers, and also 
ADC and total antibody concentration will be listed for each assessment time point. The 
frequency and percentage of participants with positive and negative anti-drug antibody will 
be summarized for each assessment time and overall for each participant. The conclusive 
results will be based on the total antibody concentration. The details of the planned displays 
are presented in Appendix 12: List of Data Displays. 
Summary of biomarker change from baseline by scheduled visits using mean, median, 
standard deviation, minimum and maximum will be provided. A listing of biomarker will 
be provided. The details of the planned displays are presented in Appendix 12: List of Data 
Displays. 
 
 


 
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10. 
PHARMACOKINETIC ANALYSES 
The pharmacokinetic analyses will be based on the “Pharmacokinetic (PK)” population, 
unless otherwise specified. 
Concentration-time data collected under protocol amendment 3 will be analysed using 
standard non-compartmental methods; some parameters will be determined for all 
participants and cycles. Full details are presented in Appendix 12: List of Data Displays. 
10.1. 
Drug Concentration Measures 
Refer to Appendix 5: Data Display Standards & Handling Conventions (Section 14.5.3) 
10.1.1. 
Non-compartmental Analysis 
• 
Pharmacokinetic parameters described in Table 2 below, will be determined 
separately for each analyte, as data permit. 
• 
The pharmacokinetic parameters under protocol amendment 3 or later will be 
calculated by standard non-compartmental analysis according to current working 
practices and using Phoenix WinNonlin, version 6.3 or later, as data permit. 
• 
The pharmacokinetic parameters CEOI and Ctrough will be determined directly from 
the concentration-time dataset for the other cycles under protocol amendment 3 and 
for participants enrolled prior to protocol amendment 3, as data permit.  
Note: For the dosing occasions with only predose and end of infusion samples, the 
end of infusion concentration (CEOI) will not be identified as Cmax. 
• 
All calculations of non-compartmental parameters will be based on actual sampling 
times. 
Table 2 
Derived Pharmacokinetic Parameters 
Parameter 
Parameter Description 
AUC(0-t) 
Area under the concentration-time curve from time zero to the time of the last quantifiable 
concentration (C(t)) will be calculated using the linear trapezoidal rule for each incremental 
trapezoid and the log trapezoidal rule for each decremental trapezoid 
AUC(0-) 
Area under the concentration-time curve during the dosing interval (=504h, this parameter 
will be calculated only for ADC and total antibody) 
AUC(0-
168) 
Area under the concentration-time curve from time 0 to 168h (This parameter will be 
calculated only for cys-mcMMAF) 
AUC(0-∞) 
Area under the concentration-time curve extrapolated to infinity will be calculated as:  
AUC = AUC(0-t) + C(t) / lambda_z  
%AUCex 
The percentage of AUC (0-∞) obtained by extrapolation (%AUCex) will be calculated as: 
[AUC(0-inf) – AUC(0-t)] / AUC(0-inf) x 100 
Cmax 
Maximum observed concentration, determined directly from the concentration-time data for 
each cycle.  Cmax will not be derived when only predose and EOI samples were collected. 
tmax 
Time to reach Cmax, determined directly from the concentration-time data for each cycle 


 
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Parameter 
Parameter Description 
C, 
Ctrough 
Trough concentration prior to the next dose for each cycle 
CEOI 
Observed plasma concentration at the end of infusion 
t½ 
Apparent terminal half-life will be calculated as:  
t½ = ln(2) / lambda_z  
tlast 
Time of last observed quantifiable concentration  
CL 
Clearance (This parameter will be calculated only for ADC and total antibody) 
CL/weight 
CL normalized by body weight (This parameter will be calculated only for ADC and total 
antibody) 
Vss 
Volume of distribution at steady state (This parameter will be calculated only for ADC and 
total antibody) 
Vss/weight 
Vss normalized by body weight (This parameter will be calculated only for ADC and total 
antibody) 
z, 
lambda_z 
Terminal phase rate constant  
 
10.2. 
Population of Interest  
The pharmacokinetic analyses will be based on the PK population, unless otherwise 
specified. 
10.3. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 12: List of Data Displays, based 
on GSK data standards and statistical principles. Unless otherwise specified, endpoints / 
variables defined in Section 10.1.1 will be summarised using descriptive statistics 
descriptively (mean, standard deviation, median, minimum, maximum, geometric mean, 
and the standard deviation, CV%, and 95% CI of parameters values) by cycle, graphically 
presented (where appropriate) and listed. 
10.3.1. 
Statistical Methodology Specification 
The following pharmacokinetic statistical analyses will only be performed if sufficient 
data are available. 
10.3.1.1. 
 Concentration-Time Data 
Concentration-time data will be summarized (when appropriate) using mean, median, 
standard deviation, minimum, and maximum, i.e. by planned time point and dose level 
for belantamab mafodotin (ADC, total antibody and cys-mcMMAF). 
Linear and semi-logarithmic individual concentration-time profiles, and mean and 
median profiles (when appropriate) will be plotted for belantamab mafodotin (ADC, total 
antibody and cys-mcMMAF). 


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11. 
PHARMACOKINETIC / PHARMACODYNAMIC 
ANALYSES 
11.1. 
Exposure-Response for Efficacy and Safety Endpoints 
If deemed appropriate and if data permit, exposure-response relationships between 
belantamab mafodotin exposure (e.g., dose, dose intensity, concentration, Cmax, or 
AUC) and clinical activity and/or toxicity (e.g., response, corneal event, AESIs) may be 
explored using population methods. If data permit, the effects of covariates may be 
explored.  Details of these analyses will be reported under a separate RAP, and the 
results of this analysis will be provided in a separate report. 
11.2. 
Concentration-QTc Analyses 
For each ECG assessment, the individual participant’s QTcF change from baseline will 
be calculated and will be merged with time-matched PK concentration values for the 
timepoints at which they are available. QTcF change from baseline (y-axis) will be 
plotted against the PK concentration data (x-axis) separately for each analyte (ADC, total 
mAb, and cys-mc-MMAF). If appropriate, linear regression analyses may be performed 
for each analyte-QTcF plot.  
 
 


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13. 
REFERENCES 
NA. 


 
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14. 
APPENDICES 
14.1. 
Appendix 1: Exclusions from Per Protocol Population 
This study does not have per protocol population. 


 
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14.2. 
Appendix 2: Schedule of Activities 
Study 
Assessments 
Scree
n1 
Cycle 1 
Day 12 
Cycle 1 
Day 2 
Cycle 1 
Day 4 
Cycle 
1 Day 
8 
Cycle 1 
Day 15 
Treatment Period3 Cycle = 21 
days 
End 
of 
Treatment 
Follow-up4 
PD Follow-up5 
D1 of C2 - CX 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Baseline 
Demographics 
X 
 
 
 
 
 
 
 
 
Medical 
History 
including disease 
history 
and 
characteristics 
X 
 
 
 
 
 
 
 
 
Physical Exam 
X 
X 
 
 
 
 
X every 3 weeks 
X 
X 
Safety 
 
Ocular Exam 
X6 
 
 
 
 
 
X7 
X7 
X8 
ECOG 
Performance 
Status 
X 
 
 
 
 
 
X every 3 weeks 
X 
 
Vital Signs (BP, 
HR, 
Body 
Temperature) 9, 10 
X 
X 
 
 
X 
X 
X 
X 
 
Weight9 
and 
Height 
X 
Weight 
only 
 
 
 
 
Weight only 
Weight only 
 
Hematology11 
X 
X 
 
X 
X 
X 
X every 3 weeks 
X 
 
Clinical 
chemistry11 
X 
X 
X 
X 
X 
X 
X every 3 weeks 
X 
X11 
Urine Dipstick11 
X 
X 
 
 
 
 
X every 3 weeks 
X 
X 
eGFR (by MDRD 
formula- 
see Appendix 8) 
X 
X 
 
 
 
 
X every 3 weeks 
X 
 
Spot 
urine 
for 
creatinine/albumin 
ratio12 
X 
X 
 
 
 
 
Cycle: 3, 5, 7 and Every other 
cycle thereafter 
X 
 
CRP 
X 
 
 
 
 
 
X every 3 weeks 
X 
 
HBsAg, 
HBcAb, 
and hepatitis C 
Ab.13 
X 
 
 
 
 
 
 
 
 
Troponin I14 
X 
 
 
 
 
 
 
 
 
BNP15 
X 
 
 
 
 
 
 
 
 
Pregnancy Test 9, 
16 
X 
X 
 
 
 
 
X 
X 
X16 
ECHO17 
X 
 
 
 
 
 
as clinically indicated 
 
 
12-lead ECG9, 18 
X 
X18 
X18 
X18 
X18 
X18 
X. 
X 
 
PK and ADA 
 
PK19 
 
X19 
X19 
X19 
X19 
X19 
X19 
X20 
 
ADA21 
 
X21 
 
 
 
 
X21 
X21 
 
Disease Evaluation 
 
2 Microglobulin 
X 
 
 
 
 
 
 
 
 
Response 
assessment22 
 
 
 
 
 
 
X every 3 weeks 
X23 
X 
 Skeletal survey24 
X 
 
 
 
 
 
As clinically indicated 25 
 
 
Imaging 
for 
Extramedullary 
disease26 
X 
 
 
 
 
 
C5, C9, C13 and C17, 
every12 
weeks 
then 
as 
clinically indicated 26 
X 27 
X 
UPEP 
(Urine 
Protein 
Electrophoresis) 
24 
hr 
urine 
collection 
X 
 
 
 
 
 
X every 3 weeks 
X 
X 
Urine 
Immunofixation 
X 
 
 
 
 
 
At time of first achieving CR or 
suspected PD after CR or 
sCR 
At time of first 
achieving CR 
or suspected 
PD after CR 
or sCR 
At time of first 
achieving CR or 
suspected PD 
after CR or sCR 


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Study 
Assessments 
Scree
n1 
Cycle 1 
Day 12 
Cycle 1 
Day 2 
Cycle 1 
Day 4 
Cycle 
1 Day 
8 
Cycle 1 
Day 15 
Treatment Period3 Cycle = 21 
days 
End 
of 
Treatment 
Follow-up4 
PD Follow-up5 
D1 of C2 - CX 
SPEP 
(Serum 
Protein 
Electrophoresis) 
X 
 
 
 
 
 
X every 3 weeks 
X 
X 
Serum 
immunofixation 
X 
 
 
 
 
 
At time of CR or suspected 
PD after CR or sCR 
At time of CR 
or suspected 
PD after CR 
or sCR 
At time of CR or 
suspected PD 
after CR or sCR 
Serum 
Kappa, 
lambda free LC, 
FLC ratio 
X 
 
 
 
 
 
X every 3 weeks 
X 
X 
Calcium corrected 
for 
albumin 
(serum) 
X 
 
 
 
 
 
X every 3 weeks 
X 
X 
IgG, IgM, IgA 
X 
X 
 
 
 
 
X every 3 weeks 
X 
X  
IgD/E28 
X 
X 
 
 
 
 
X every 3 weeks 
X 
X 
Bone Marrow Aspiration / biopsy 
FISH testing on 
bone marrow29 
X 
 
 
 
 
 
 
 
 
BM for disease 
assessment31 
X 
 
 
 
 
 
At the time of CR (always) or 
at time of suspected PD (only 
if not evident otherwise) 
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 
Bone marrow to 
assess sCR by 
(IHC)32 
 
 
 
 
 
 
X32 
Only if CR 
has 
been 
achieved on 
this visit. 
Only if CR have 
been achieved 
on this visit 
Biomarker 
 
Study treatment 
 
Premedication 
if 
needed 
 
X 
 
 
 
 
X 
 
 
Belantamab 
mafodotin 
administration34 
 
X 
 
 
 
 
X 
 
 
Preservative-free 
artificial tears35 
 
X 
 
 
 
 
Everyday until end of Study 
treatment 
 
 
Adverse Events36 
 
X 
X 
X 
X 
X 
X 
 
Concomitant 
Medications 
X 
X 
X 
 
X 
X 
X 
 
Health Outcomes 
OSDI37 
X 
X 
 
 
 
 
X  every 3 weeks 
X 
X 
Abbreviations: 
ADA = Anti-drug Antibody; ALP = alkaline phosphatase; BM = bone marrow; BNP = B-type natriuretic peptide; BP = blood pressure; C1D1 = Cycle 1 
Day 1, etc.; CK = creatine kinase;  CRP = C-reactive protein; EM = extramedullary; EOI = End of Infusion; FISH = fluorescence in situ hybridization; 
FLC = free light chain; HR= heart rate; Ig = immunoglobulin; PK = Pharmacokinetics; QID = 4 times a day; SOI = start of infusion; SPEP = serum 
protein electrophoresis; UPEP = urine protein electrophoresis; OSDI = Ocular Surface Disease Index. 
 
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 C1D1 unless 
otherwise specified. 
2.
Assessments scheduled on days of dosing must be done prior to drug administration, unless otherwise specified. All other assessments 
can be done r3 days unless otherwise specified. 
3.
Belantamab mafodotin will be administered intravenously on Day 1 (D1) of every 21-day cycle until disease progression, death, 
unacceptable toxicity, withdrawal of consent or end of study. 
4.
The End of treatment (EOT) follow-up visit is to assess any residual AEs or toxicities associated with Study treatment. The visit should 
occur -within 45 days after last dose or before the start any new anti-cancer therapy.  
5.
PD follow-up once every 21 days: Participants who discontinue IP for a reason other than PD, disease evaluations will continue to be 
performed once every 21 days (±7 days) until confirmed PD, death, start of a new anticancer treatment, withdrawal of consent, or end of 
the study whichever occurs first.  
6.
Screening examination will be performed by an ophthalmologist (or an optometrist if an ophthalmologist is not available) within 21 days 
prior to first dose. See Protocol Section 8.3.9 for the list of ophthalmic exam procedures. 
7.
On-study ophthalmic exams to be performed by an ophthalmologist (or an optometrist if an ophthalmologist is not available) pre-dose 
every 3 weeks (schedule of assessment window should be within 5 days prior to dosing, all efforts should be made to schedule as close 
to dosing as possible). After the 6th dose of belantamab mafodotin (no schedule of assessment window needed): If there are no significant 
(Grade 2 or above) ocular symptoms or vision changes the frequency of ophthalmologic exams may be decreased to every 3 months until 
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end of treatment. In case of persistent ocular exam findings, newly developed ocular symptoms or vision changes, further ocular exams 
should be performed at least every cycle until resolution (to Grade 1 or baseline) or more frequently as clinically indicated by the qualified 
eye care specialist(Protocol Appendix 9). See Protocol Section 8.3.9 for the list of ophthalmic exam procedures. 
8. 
Additional exams may be performed by the ophthalmologist (an optometrist if an ophthalmologist is not available), as clinically indicated.  
9. 
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:  ECG, weight, vitals, pregnancy test. Please follow the visit schedule in the SOA above, and perform 
these activities prior to a belantamab mafodotin infusion. 
10. 
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, end of infusion (EOI), and 1 hour post EOI. On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 
minutes prior to SOI), and at EOI. On days where vital sign time points align with PK sampling time points, vital signs must 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.  
11. 
Refer to Protocol Table 9 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 Day 1 of Cycle 1. Creatinine only is required at PD visits (not a full 
chemistry).  
12. 
Creatinine / albumin ratios (spot urine from first void) at screening and C1, C3, C5, C7 and every other cycle thereafter (local labs or 
central if local not available). 
13. 
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 negative- participant is eligible).  
14. 
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 must be measured.  
15. 
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 must be measured. 
16. 
Perform only in women of childbearing 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, follicle stimulating hormone (FSH) and estradiol (as needed in women of non-child bearing potential only) should 
be performed at local lab. See Protocol Section 5.1, Section 8.3.5, and Appendix 4 for more details. 
a. 
Final pregnancy test (serum or urine) must be performed in women of childbearing potential at the EOT Visit, and 8 
months after the last dose of study treatment may be via a urine pregnancy test kit mailed to the participant’s home with 
results reported by telephone.  
17. 
Echocardiography for LVEF performed within 3 months of screening are acceptable as screening value. For participants with an abnormal 
LVEF (per institutional standards), the participant is to follow-up with a cardiologist. 
18. 
ECGs on dosing days: Triplicate ECGs to be performed at pre-dose (within 30 minutes prior to SOI) and EOI at cycle 1. Triplicate ECGs 
should be collected prior to PK sample on Cycle 1 Day 2, Day 4, Day 8 and Cycle 1 Day 15. Single ECG at screening, at all other cycles, 
and End of Study Treatment On days where ECG time points align with PK sampling time points, ECGs must be performed within 30 
minutes prior to PK samples being drawn (PK sample must be taken at the exact nominal time). ECGs will be collected and stored at site. 
See SRM for details on collection regarding ECGs. 
19. 
PK samples to be taken in all participants for belantamab mafodotin ADC, total antibody and cys-mcMMAF measurements on: 
- C1D1 at pre-dose (within 30 minutes prior to SOI), at the end of infusion (EOI) (+5 min), 2 h post-SOI (±15 min), 4 h post-SOI (±15 min), 
8 h post-SOI (±1 h), 24 h post-SOI (±2 h); 
- C1D4 anytime (±1 day);  
- C1D8 anytime (±1 day);  
- C1D15 anytime (±1 day);   
- C1D22 anytime (±1 day) (collect one PK sample only if the dose for the next cycle is delayed; this sample will combined) 
- For C2D1, C4D1, C6D1, C9D1, and C12D1, collect samples at pre-dose (within 30 min prior to SOI) and at the EOI (+5 min);  
- For every six cycles after C12 (e.g., C18, C24, etc.), collect one sample at pre-dose (within 30 min prior to SOI). However, one year after 
the first dose of last subject, PK samples will only be collected for the interpretation of ADA results in the following visits. 
20. 
Collect 1 PK sample at each participant’s final visit.  
21. 
All ADA samples will be collected prior to each infusion at C1, C2, C4, C6, C9, C12, and every 6 cycles thereafter (C18, C24, etc.) until 
end of treatment (dosing days only) and at the last visit. 
22. 
Disease Response Assessment:  Response assessment must be conducted Q3W based on standard disease laboratory tests (serum 
and urine M protein test, FLC, IgD/E, if applicable), Ca corrected for albumin, bone marrow aspirate (in case of CR, or suspected PD if not 
evident otherwise). Assessment based on imaging has to be included in participants with extramedullary disease at indicated time points. 
Response evaluation will be performed according to the IMWG Uniform Response Criteria for Multiple Myeloma 2016.  
23. 
For participants who are discontinuing IP due to PD the confirmation must performed on a different date from a different blood collection 
within 14 days of the original disease progression. This may be performed at the at EOT follow-up visit.  
24. 
Skeletal Survey: Imaging of bones for lytic lesions by a method aligned with the institutional guidance (X-ray, CT, or [Computed 
tomography], or MRI [Magnetic resonance imaging]). Skeletal survey results within 30 days prior to C1D1 are acceptable.  
25. 
Only if clinically indicated or if worsening clinical symptoms suggest PD.  
26. 
Imaging is only required for participants with extramedullary disease (CT, MRI, or PET [Positron Emission Tomography]//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 (i.e., if PET scan was used as baseline, participant needs to be followed by PET 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). Evaluations should be performed by the same method as at screening.  
27. 
In participants with extramedullary MM, if the last radiographic assessment occurred ≥8 weeks prior to the participant’s withdrawal from 
study treatment, and progressive disease has NOT been documented –then a new assessment (presence or absence extramedullary 
disease) should be obtained at the time the participants withdrew from study treatment. 
28. 
Only required for participants with IgD/E myeloma, where serum m-component cannot be followed otherwise 
29. 
FISH testing at least for: t (4;14), t (14;16), 17p13del, and +1q21. FISH results from samples taken within 60 days prior to first dose are 
acceptable. If this cannot be performed at a local lab the samples can be sent to the central lab 


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30.
31.
Bone Marrow for disease assessment performed within 14 days prior to first dose is acceptable.  
32.
Bone marrow biopsy for IHC to confirm sCR after achieving a CR. 
33.
34.
Belantamab mafodotin administration: Study drug administration r3-day window.  
35.
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. 
36.
All related SAEs are to be collected from consent through PD follow-up. 
37.
Additional assessments may be conducted for those participants who experience a worsening in visual function. Participants who 
discontinue participation in the study will continue to be assessed during follow-up until resolution of visual symptoms. Continue to follow 
up with participants via telephone who are still experiencing visual symptoms even after discontinuation 
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14.3. 
Appendix 3: Assessment Windows 
All assessments on study must be performed on a calendar schedule in Appendix 2: 
Schedule of Activities 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, 
and PD follow-up visits have a ±7 days window. 
For analysis endpoints, the analysis visit will be re-mapped by the assessment time 
windows. In general, the summary tables will only be displayed by planned time points 
and visits, unless otherwise specified. 
 


 
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14.4. 
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events 
14.4.1. 
Study Phases 
Assessments and events will be classified according to the time of occurrence relative to 
the start and/or stop date of the study treatment. The earliest and latest exposure treatment 
start and stop dates will be used to determine whether an assessment or event was pre-
treatment, on-treatment or post-treatment. If it is not possible to tell whether an assessment 
or event was on-treatment or not it will be considered as on-treatment. 
Study Phase 
Definition 
Pre-Treatment  
Date ≤ Study Treatment Start Date 
On-Treatment 
Study Treatment Start Date < Date ≤ Study Treatment Stop Date + 70 days 
Post-Treatment 
Date > Study Treatment Stop Date + 70 days 
NOTES:  
• 
Time of study treatment dosing and assessments and events should be considered, if collected, then the study 
phases will be re-defined as following: 
Pre-Treatment: Date < Study Treatment Start Date 
On-Treatment: Study Treatment Start Date ≤ Date ≤ Study Treatment Stop Date + 70 days 
Post- Treatment: Date > Study Treatment Stop Date + 70 days 
 
Concomitant Medication start and end dates will be assigned to study time periods in 
relation to first dose of study treatment as defined below. The start date references time 
flag variables and end date reference time flag variables will be added to the concomitant 
medication datasets, respectively. 
• 
Start relative to treatment: Assign to 'BEFORE' if start date is prior to study 
treatment start date or if subject has not taken any study treatment or (start date is 
missing and end date is before study treatment start date). Else assign to 'DURING' if 
the start date falls into the on-treatment period as defined above or if subject is 
ongoing (not all study treatment discontinuation records completed) or start date is 
missing. Else assign to 'AFTER' if start date is after the on-treatment period. 
• 
End relative to treatment: Assign to 'BEFORE' if end date is prior to study treatment 
start date or if subject has not taken any study treatment. Else assign to 'DURING' if 
start date falls into the on-treatment period or if subject is ongoing (not all study 
treatment discontinuation records completed) or (end date is missing and start 
relative to treatment not 'AFTER'). Else assign to 'AFTER' if start date is after the 
on-treatment period or (end date is missing and start relative to treatment='AFTER').  
Concomitant medication starts relative to treatment and end relative to treatment flags are 
used to select data to include in the Concomitant Medication summaries as follows: 
• Summary of Concomitant Medications: This summary will contain medications 
including those with start date prior to study treatment start date and continue 
(missing end date or end date after study treatment start date) on therapy. Note that 
any medications with start date and end date prior to study treatment start date will be 
excluded. In addition, any medication that was started during post-therapy will be 


 
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excluded. Include concomitant medication records where start relative to treatment in 
('BEFORE','DURING') and end relative to treatment in ('DURING','AFTER'). 
• Summary of Concomitant Medications with On-Therapy Onset: This summary will 
contain medications with start date after study treatment start date. In addition, any 
medication that was started during post-therapy (see above for definition of post-
therapy) will be excluded. Include concomitant medication records where start 
relative to treatment in ('DURING') and end relative to treatment in 
('DURING','AFTER'). 
 


 
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14.4.2. 
Treatment Emergent Flag for Adverse Events 
Flag 
Definition 
Treatment 
Emergent 
• 
Study Treatment Start Date ≤ AE Start Date ≤ Study Treatment Stop Date + 70 
days. 
NOTES:  
• 
If the study treatment stop date is missing, then the AE will be considered to be On-Treatment. 
• 
Time of study treatment dosing and start/stop time of AEs should be considered, if collected. 
 


 
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14.5. 
Appendix 5: Data Display Standards & Handling Conventions 
14.5.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software 9.4 will be used. 
Reporting Area 
HARP Server 
: us 1salx00259 
HARP Compound 
: GSK2857916/mid208465 
Analysis Datasets  
• 
Analysis datasets will be created according to CDISC standards 
Generation of RTF Files 
• 
Rich Text Format (RTF) files will be generated for the final reporting effort for use in writing the CSR. 
14.5.2. 
Reporting Standards 
General 
• 
The current GSK Statistical Display Standards in the GSK Standards Library (IDSL) will be applied for 
reporting, 
unless 
otherwise 
stated 
(Library 
Location: 
https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx): 
• 
4.03 to 4.23: General Principles 
• 
5.01 to 5.08: Principles Related to Data Listings 
• 
6.01 to 6.11: Principles Related to Summary Tables 
• 
7.01 to 7.13: Principles Related to Graphics  
• 
Do not include participant level listings in the main body of the GSK Clinical Study Report. All 
participant level listings should be located in the modular appendices as ICH or non-ICH listings 
Formats 
• 
GSK Statistical Display Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for 
reporting of data based on the raw data collected, unless otherwise stated. 
• 
Numeric data will be reported at the precision collected on the eCRF. 
• 
The reported precision from non eCRF sources will follow the GSK Standard Statistical Display 
Principles but may be adjusted to a clinically interpretable number of DP’s. 
Planned and Actual Time 
• 
Reporting for tables, figures and formal statistical analyses: 
• 
Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated. 
• 
The impact of any major deviation from the planned assessment times and/or scheduled visit days 
on the analyses and interpretation of the results will be assessed as appropriate. 
• 
Reporting for Data Listings:  
• 
Planned and actual time relative to study drug dosing will be shown in listings (Refer to GSK 
Standard Statistical Display Principle 5.05.1). 
• 
Unscheduled or unplanned readings will be presented within the participant’s listings.  
Unscheduled Visits 
• 
Unscheduled visits will not be included in summary tables and/or figures that need to be summarized 
by visits. 
• 
All unscheduled visits will be included in listings. 


 
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Descriptive Summary Statistics 
Continuous Data 
Refer to GSK Standard Statistical Display Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• 
Refer to GSK Standard Statistical Display Principals 7.01 to 7.13. 
 
14.5.3. 
Reporting Standards for Pharmacokinetic 
Pharmacokinetic Concentration Data 
PC Windows Non-
Linear (WNL) File 
PC WNL file (CSV format) for the non compartmental analysis by Clinical 
Pharmacology Modelling and Simulation function will be created according to 
Standards for the Transfer and Reporting of PK Data document. Note: Concentration 
values will be imputed as per GUI_51487 
Descriptive Summary 
Statistics, Graphical 
Displays and Listings 
Refer to the GSK Standard PK Display Standard. 
Refer to the GSK Standard Statistical Display Principle 6.06.1. 
Note: Concentration values will be imputed as per GUI_51487 for descriptive 
summary statistics/analysis and summarized graphical displays only.  
NONMEM/Pop 
PK 
File 
Not applicable. 
NONMEM/PK/PD 
File 
Not applicable. 
Pharmacokinetic Parameter Derivation 
PK Parameter to be 
Derived 
by 
Programmer 
The following PK parameter will be derived by the Programmer:  
• 
Accumulation ratios based on Cycle 1 and Cycle 4 CEOI and Ctrough 
values 
Pharmacokinetic Parameter Data 
Is NQ impacted PK 
Parameters 
Rule 
Being Followed 
Yes, refer to [Standards for Handling NQ Impacted PK Parameters]. 
Descriptive Summary 
Statistics, Graphical 
Displays and Listings 
Refer to GSK Standard PK Display Standard. 
 
 


 
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14.6. 
Appendix 6: Derived and Transformed Data 
14.6.1. 
General 
Multiple Measurements at One Analysis Time Point 
• 
If there are two or more values within a time window (as per Section 14.3) the value closest to the 
target day for that window will be used for summary tables. If values are the same distance from the 
target, then the mean will be taken, but if listed, all data will be presented. 
• 
Participants having both High and Low values for Normal Ranges at any post-baseline visit for safety 
parameters will be counted in both the High and Low categories of “Any visit post-baseline” row of 
related summary tables. This will also be applicable to relevant Potential Clinical Importance summary 
tables. 
Study Day 
• 
Calculated as the number of days from First Dose Date: 
• 
Ref Date = Missing              → Study Day = Missing  
• 
Ref Date < First Dose Date → Study Day = Ref Date – First Dose Date 
• 
Ref Data ≥ First Dose Date → Study Day = Ref Date – (First Dose Date) + 1     
 
14.6.2. 
Study Population 
Age 
• Age will be calculated based on the date of first dose. 
• Only year of birth is collected on the eCRF, therefore day and month of birth are imputed as 
‘30JUN’ in order to derive age. 
• 
Birth date will be presented in listings as ‘YYYY’. 
Body Mass Index (BMI) 
• 
Calculated as Weight (kg) / [Height (m)2] 
Extent of Exposure 
• Number of days of exposure to study drug will be calculated based on the formula:   
Duration of Exposure in Days = min(Last infusionDate+20, Death date) – First infusion 
Date + 1 
• Participants who were enrolled but did not report a treatment start date will be categorised 
as having zero days of exposure.  
• The cumulative dose will be based on the formula: 
Cumulative Dose (mg/kg) = Sum of Dose at Each Cycle 
• Dose intensity will be calculated based on the formula: 
• Dose intensity (mg/kg/3 week) = Cumulative Dose/((last infusion date – first infusion 
date + 21)/21) 
14.6.3. 
Efficacy 
Objective Response Rate ORR 
• ORR will be calculated based on the formula: 
ORR = Number of Participants with a Confirmed Partial Response (PR) or Better / Number of 
Participants in All Treated Population 


 
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14.6.4. 
Safety 
Adverse Events of Special Interest (AESI) 
• 
AESI includes corneal events, thrombocytopenia and infusion related reactions 
Laboratory Parameters 
• 
If a laboratory value which is expected to have a numeric value for summary purposes, has a non-
detectable level reported in the database, where the numeric value is missing, but typically a character 
value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than x in the comment field) is 
present, the number of significant digits in the observed values will be used to determine how much to 
add or subtract in order to impute the corresponding numeric value.  
• 
Example 1: 2 Significant Digits = ‘< x ‘ becomes x – 0.01  
• 
Example 2: 1 Significant Digit = ‘> x’ becomes x + 0.1  
• 
Example 3: 0 Significant Digits = ‘< x’ becomes x – 1  
14.6.5. 
Pharmacokinetic 
PK 
• 
Plasma sample analysis will be performed under the control of GSK Bioanalysis 
Immunogenicity and Biomarkers (BIB) group, the details of which will be included in 
the Study Reference Manual (SRM). Belantamab mafodotin, total antibody, and cys-
mcMMAF plasma concentrations will be determined using the currently validated 
methodology. The actual sampling times, if different from protocol, will be used in the 
PK calculations. Please refer to the rules in Section 14.7.2 for the plasma concentrations 
below Limit of quantification (LOQ). 
• 
Belantamab mafodotin, total antibody, and cys-mcMMAF plasma concentration-time 
data will be analyzed by non-compartmental methods with WinNonlin 6.3 or above and 
derived PK parameters will be summarised and listed. Derived Pharmacokinetic 
parameters will be summarized by cycle and dose level. Mean, standard deviation, 
median, minimum, maximum, geometric mean, and the standard deviation, CV%, and 
95% CI of parameters values will be provided; Individual concentration, linear and semi-
logarithmic individual concentration-time profiles, and mean and median profiles (when 
appropriate) will be provided. 
 


 
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14.7. 
Appendix 7: Reporting Standards for Missing Data 
14.7.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• 
Participant study completion (i.e. as specified in the protocol) was defined as completed 
all scheduled visit and completed exit visit.  
• 
All available data from participants who were withdrawn from the study will be listed and 
all available planned data will be included in summary tables and figures, unless 
otherwise specified.  
• 
The Withdrawal visit will be slotted as per Appendix 3: Assessment Windows or will be 
summarised as the withdrawal visit. 
14.7.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• 
Missing data occurs when any requested data is not provided, leading to blank fields 
on the collection instrument: 
o These data will be indicated by the use of a “blank” in participant listing displays. 
Unless all data for a specific visit are missing in which case the data is excluded 
from the table.  
o Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such. 
Outliers 
• 
Any participants excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report. 
PK 
• 
Concentrations which are below the LLQ (“lower limit of quantification” for the analyte 
in question) are listed as NQ in the raw concentration data provided by DMPK. Several 
derived variables exist for the imputation of these concentrations.  
• 
The following variables exist in the PKCNC dataset for different imputations of the raw 
concentration data; 
PCORRES: 
Original result 
PCSTRESN: 
Original result in standard units 
PCSTIMPN: 
Imputed result for use in the calculation of summary statistics 
PCSTIMSN: 
Imputed result for individual concentration plots 
PCWNLN: 
Imputed result for use in WinNonlin analysis 
• 
The imputation of NQs for variables in the PKCNC file will be based on that defined in 
GUI_51487, under the section “How to Handle Values Below the Quantification Limit”. 
A brief summary is provided in the table below.  
Variable  
Leading 
NQ 
Single 
NQ 
between 
measurable 
concentrations 
More than one 
consecutive 
NQ between 
measurable 
concentrations 
Measurable 
concentrations 
after 
more 
than 
one 
consecutive 
mid-profile 
NQ* 
Trailing NQ 
(consecutive 
NQs in the 
tail) 
PCSTIMPN 
0 
NULL 
0 
NULL 
0 
PCSTIMSN 
0 
NULL 
0 
No Action 
NULL 
PCWNLN 
0 
NULL 
NULL 
NULL 
NULL 


 
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Element 
Reporting Detail 
 
* a mid-profile NQ is defined as any NQ where measurable concentrations exist both before 
and after that NQ in the profile 
14.7.2.1. 
Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant listing displays. 
• 
Imputed partial dates will not be used to derive study day, duration (e.g. duration 
of adverse events), or elapsed time variables. In addition, imputed dates are not 
used for deriving the last contact date in the overall survival analysis dataset.  
• 
Imputed dates will not be displayed in listings. However, where necessary, display 
macros may impute dates as temporary variables for the purpose of sorting data 
in listings only. In addition, partial dates may be imputed for ‘slotting’ data to study 
time periods or for specific analysis purposes as outlined below. 
Adverse Events 
• 
The eCRF allows for the possibility of partial dates (i.e., only month and year) to 
be recorded for AE start and end dates; that is, the day of the month may be 
missing. 
o Missing Start Day: First of the month will be used unless this is before the 
start date of study treatment; in this case the study treatment start date will 
be used and hence the event is considered On-treatment as per Appendix 
4: Study Phases and Treatment Emergent Adverse Events. 
o Missing Stop Day: Last day of the month will be used. 
• 
Completely missing start dates will remain missing, with no imputation applied. 
Consequently, time to onset and duration of such events will be missing. 
• 
Completely missing end dates will remain missing, with no imputation applied. 
Consequently, duration of such events will be missing.  
Concomitant 
Medications/Medical 
History 
• 
 Partial dates for any concomitant medications recorded in the CRF will be 
imputed using the following convention: 
o If the partial date is a start date, a '01' will be used for the day and 'Jan' will 
be used for the month 
o If the partial date is a stop date, a '28/29/30/31' will be used for the day 
(dependent on the month and year) and 'Dec' will be used for the month. 
• 
The recorded partial date will be displayed in listings. 
Covariates for 
efficacy analysis 
(Date of initial 
diagnosis/ Last 
recurrence/ 
Last progression)  
• 
If both month and day are missing, first of January will be used 
• 
If only day is missing, first of the month will be used 
Treatment end date 
• If there is more than one study treatment, imputation of missing treatment end 
date will be applied to all applicable treatments following rules below and 
treatment end date is the latest treatment end date across all study treatments. 
In general, completely missing end dates are not imputed, with the following 
exceptions for imputation of missing treatment end date at interim analyses. 
• For imputation of missing exposure end date at an interim analysis when 
participants are still on treatment, the following conventions will be applied: 


 
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Element 
Reporting Detail 
o If the missing end date is in the last exposure record, the earliest of: the 
date of the data cut-off, the date of withdrawal from the study, or the death 
date will be used  
o If the missing end date is not in the last exposure record, treatment start 
date for the record will be used 
• The imputed treatment end date will be used to calculate cumulative dose and 
duration of treatment as specified in Section 14.6.2. 
• 
If treatment end date is missing for a cycle, treatment start date for the cycle will 
be used. 
 
 
 


 
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14.8. 
Appendix 8: Values of Potential Clinical Importance 
14.8.1. 
Laboratory Values 
Reference ranges for all laboratory parameters collected throughout the study are 
provided by the laboratory. A laboratory value that is outside the reference range is 
considered either high abnormal (value above the upper limit of the reference range) or 
low abnormal (value below the lower limit of the reference range). Note: a high abnormal 
or low abnormal laboratory value is not necessarily of clinical concern. The laboratory 
reference ranges will be provided on the listings of laboratory data. Clinical laboratory 
test results outside of the reference range will be flagged in the listings. 
To identify laboratory values of potential clinical importance, National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0) will be used to 
assign grades to the relevant laboratory parameters. NCI-CTCAE v5.0 can be found at 
http://ctep.cancer.gov/reporting/ctc.html.  
For laboratory data which are not listed in the NCI CTCAE v5.0, a summary of values 
outside the normal range will be provided. 
14.8.2. 
ECG Parameters and Vital Signs 
For ECG and vital signs, outputs per the most updated IDSL standard up to the RAP 
effective date will be provided. 
Unless otherwise specified, ECG displays will be based on central reading. 
 


 
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14.9. 
Appendix 9: Pharmacokinetic / Pharmacodynamic Analyses 
14.9.1. 
Pharmacokinetic / Pharmacodynamic Dataset Specification 
If deemed appropriate and if data permit, dose/exposure - objective response relationships 
between belantamab mafodotin dose/exposure and clinical activity may be explored based 
on pooled data from Study 208465 and overseas studies using population methods. 
Dose/exposure will be assessed based on dose intensity, duration of exposure in days, 
Cmax and AUC. Clinical activity will be assessed based on objective response which is 
defined as the confirmed stringent complete response (sCR), complete response (CR), very 
good partial response (VGPR), and partial response (PR) as assessed by IMWG. The 
response is a binary term (e.g., 0 or 1, 1 = confirmed partial response (PR) or better; 0 = 
other response or NE).  
If deemed appropriate and if data permit, dose/exposure - toxicity relationships between 
belantamab mafodotin dose/exposure and safety activity may be explored using above 
method. Safety activity will be assessed based on Dose-Limiting Toxicity (DLT). The 
response is also a binary term (e.g., 0 or 1, 1 = experienced DLT; 0 = non-experienced 
DLT). 
If data permit, the effects of covariates (e.g., race, age, body weight) may also be explored. 
The analyses will be based on the PK population, unless otherwise specified. 
14.9.2. 
Pharmacokinetic / Pharmacodynamic Methodology 
If deemed appropriate and if data permit, dose/exposure- safety/clinical activity 
relationships will be analysed using logistic regression. Generalized linear mixed model 
(GLMM) will be used which includes the terms of response of safety/clinical activity, dose 
intensity, duration of exposure in days, Cmax and AUC, If data permit, the effects of 
covariates (e.g., race, age, body weight) may also be included.  
In order to determine which terms impact the response of safety/clinical activity 
significantly, the step-by-step method will be used to select the statistical significant terms. 
The results of analyses based on the final model will be presented as estimated effect of 
selected terms, 2-sided 95% confidence intervals (CI), and associated p-values. 


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14.11. 
Appendix 11: Abbreviations & Trade Marks 
14.11.1. 
Abbreviations 
Abbreviation 
Description 
ADA 
Anti-drug antibodies 
ADC 
Antibody drug conjugate 
AE 
Adverse Event 
AUC 
Area under the curve 
BCMA 
B-cell maturation antigen 
BM 
Bone marrow 
BNP 
B-type natriuretic peptide 
BP 
Blood Pressure 
C1D1 
Cycle 1 Day 1 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence interval 
CK 
Creatine kinase 
CL 
Clearance 
Cmax 
Maximum observed concentration 
CR 
Complete response 
CRF 
Case Report Form 
CRP 
C-reactive protein 
CSR 
Clinical study report 
CT 
Computed tomography 
Ctrough 
Trough plasma concentration after repeat dose 
CV 
Coefficient of variation 
DLT 
Dose limiting toxicities 
DP’s 
Decimal Places 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EOI 
End of Infusion 
eCRF 
Electronic case report form 
eGFR 
Estimated glomerular filtration rate 
EOT 
End of treatment 
FISH 
Fluorescence in situ hybridization 
FLC 
Free light chain 
FSH 
Follicle stimulating hormone 
GFR 
Glomerular filtration rate 
GSK 
GlaxoSmithKline 
HCV 
Hepatitis C virus 
HR 
Heart rate 
ICH 
International Conference on Harmonization 
IDSL 
Integrated Data Standards Library (GSK Standards Library) 
IHC 
Immunohistochemistry 
IgA 
Immunoglobulin A 


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Abbreviation 
Description 
IgD 
Immunoglobulin D 
IgE 
Immunoglobulin E 
IgG 
Immunoglobulin G 
IgM 
Immunoglobulin M 
IMWG 
International Myeloma Working Group 
IV 
Intravenous 
LC 
Light chain  
LVEF 
Left ventricular ejection fraction 
MDRD 
Modified diet in renal disease 
MMAF 
Monomethyl auristatin-F 
MRI 
Magnetic resonance imaging 
NE 
Not Evaluable 
ORR 
Objective Response Rate 
OSDI 
Ocular Surface Disease Index 
PD 
Progressive disease 
PDMP 
Protocol Deviation Management Plan 
PET 
Positron Emission Tomography 
PK 
Pharmacokinetics 
PR 
Partial response 
Q3W 
Once every 3 weeks 
QID 
Four times a day 
QTc 
Corrected QT interval (ECG) 
QTcF 
Corrected QT interval Fridericia 
RAP 
Reporting and Analysis Plan 
RNA 
Ribonucleic acid 
RRMM 
Relapsed / refractory multiple myeloma 
RTF 
Rich Text Format 
SAC 
Statistical Analysis Complete 
SAE 
Serious adverse event 
sCR 
Stringent Complete Response 
SCT 
Stem cell transplant 
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 
t½ 
Terminal phase half-life 
Tmax 
Time of maximum observed concentration 
UPEP 
Urine protein electrophoresis 
V 
Volume of distribution 
VGPR 
Very good partial response 
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CCI


 
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14.11.2. 
Trademarks 
 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks 
not 
owned 
by 
the 
GlaxoSmithKline Group of Companies 
HARP 
 
SAS  
 
 
WinNonlin 
 
 


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Section 
Tables 
Figures 
Study Population 
1.010 to 1.xxx 
1.010 to 1.xxx 
Efficacy 
2.010 to 2.xxx 
2.010 to 2.xxx 
Dose Limiting Toxicity 
3.010 to 3.xxx 
3.010 to 3.xxx 
Safety 
4.010 to 4.xxx 
4.010 to 4.xxx 
Immunogenicity 
5.010 to 5.xxx 
5.010 to 5.xxx 
Pharmacokinetic / Biomarker 
6.010 to 6.xxx 
6.010 to 6.xxx 
Section 
Listings 
ICH Listings 
1.010 to xxx 
Other Listings 
30.010 to 30.xxx 
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Section 
Figure 
Table 
Listing 
Study Population 
POP_Fn 
POP_Tn 
POP_Ln 
Efficacy 
EFF_Fn 
EFF_Tn 
EFF_Ln 
Dose Limiting Toxicity 
DLT_Fn 
DLT_Tn 
DLT_Ln 
Safety 
SAFE_Fn 
SAFE_Tn 
SAFE_Ln 
Immunogenicity 
ADA_Fn 
ADA_Tn 
ADA_Ln 
Pharmacokinetic 
PK_Fn 
PK_Tn 
PK_Ln 
Pharmacokinetic / Pharmacodynamic 
PKPD_Fn 
PKPD_Tn 
PK/PD_Ln 
NOTES:  
x
Non-Standard displays are indicated in the ‘GSK Statistical Display Standard / Example Shell’ or ‘Programming 
Notes’ column as ‘[Non-Standard] + Reference.’ 
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Description 
SAC [1] 
Final Statistical Analysis Complete 
NOTES:  
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14.12.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
GSK Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.010 
All Treated 
ES8 
Summary of Subject Status and Reason for Study 
Withdrawal 
 
SAC [1] 
1.020 
Screened 
ES6 
Summary of Screening Status and Screening Failures 
 
SAC [1] 
1.030 
All Treated 
SD1 
Summary of Treatment Status and Reasons for 
Discontinuation of Study Treatment 
 
SAC [1] 
Protocol Deviation 
1.040 
All Treated 
DV1 
Summary of Important Protocol Deviations 
 
SAC [1] 
Population Analysed 
1.050 
Screened 
SP1 
Summary of Study Populations  
 
SAC [1] 
Demographic and Baseline Characteristics 
1.060 
All Treated 
DM1  
Summary of Demographic Characteristics 
 
SAC [1] 
Disease Characteristics 
1.070 
All Treated 
DC2 
Summary of Disease Characteristics 
 
SAC [1] 
1.080 
All Treated 
POP_T1 
Summary of Genetic Characteristics and Cytogenetics Risk 
at Screening 
 
SAC [1] 
Medical Conditions 
1.090 
All Treated 
MH1 
Summary of Current Medical Conditions 
 
SAC [1] 
Prior and Follow-Up Anti-Cancer Therapy 


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Study Population Tables 
No. 
Population 
GSK Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.100 
All Treated 
POP_T3 
Summary of Prior Anti-Cancer Therapy by Drug Class of 
Agents 
 
SAC [1] 
1.110 
All Treated 
POP_T4 
Summary of Subjects Refractory to Prior Anti-Cancer 
Therapy by Drug Class 
 
SAC [1] 
Extent of Exposure 
1.120 
All Treated 
EX1 / EX5 
Summary of Exposure to Belantamab Mafodotin 
 
SAC [1] 
1.130 
All Treated 
OEX6 
Summary of Dose Reductions of Belantamab Mafodotin 
 
SAC [1] 
1.140 
All Treated 
OEX6 
Summary of Dose Delays of Belantamab Mafodotin 
 
SAC [1] 
1.150 
All Treated 
Non-Standard 
Summary of Dose Modifications of Belantamab Mafodotin 
 
SAC [1] 
Prior and Concomitant Medications 
1.160 
All Treated 
CM8 
Summary of Concomitant Medications 
 
SAC [1] 
1.170 
All Treated 
CM8 
Summary of Blood Products 
 
SAC [1] 
1.180 
All Treated 
CM8 
Summary of Blood Supportive Care Products 
 
SAC [1] 
 
 
 


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14.12.5. 
Study Population Figures 
No figures of study population analysis. 
 
 


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Efficacy: Tables 
No. 
Population 
GSK Standard / 
Example Shell 
Title  
Programming 
Notes 
Deliverable 
[Priority] 
Response 
2.010 
All Treated 
Non-Standard 
Summary of Objective Response Rate 
 
SAC [1] 
Time-to Event Endpoint 
2.020 
All Treated 
TTE1a 
Summary of Duration of Response 
 
SAC [1] 
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14.12.7. 
Efficacy Figures 
No figures of efficacy data analysis. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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14.12.8. 
Dose Limiting Toxicity Tables 
Dose Limiting Toxicity: Tables 
No. 
Population 
GSK Standard 
/ 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Dose Limiting Toxicity (DLT) 
3.010 
DLT Evaluable 
AE19 
Summary of Dose Limiting Toxicity During the Cycle 1 of Study 
Treatment 
 
SAC [1] 
 
 


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14.12.9. 
Dose Limiting Toxicity Figures 
No figures of dose limiting toxicity. 
 
 


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14.12.10. Safety Tables 
Safety: Tables 
No. 
Population 
GSK Standard/ 
Example Shell 
Title  
Programming Notes Deliverable 
[Priority] 
Adverse Events (AEs) 
4.010 
All Treated 
AE13 
Adverse Event Overview 
 
SAC [1] 
4.020 
All Treated 
AE3 
Summary of All Adverse Events by Preferred Term 
 
SAC [1] 
4.030 
All Treated 
OAE07 
Summary of All Adverse Events by Preferred Term and Maximum Grade 
 
SAC [1] 
4.040 
All Treated 
OAE07 
Summary of All Treatment-Related Adverse Events by Preferred Term and 
Maximum Grade 
 
SAC [1] 
4.050 
All Treated 
OAE07 
Summary of Non-Serious Adverse Events by Preferred Term and Maximum 
Grade 
 
SAC [1] 
4.060 
All Treated 
AE3 
Summary of Adverse Events of Maximum Grade 3 or Higher by Preferred Term 
 
SAC [1] 
Adverse Events of Special Interest 
4.070 
All Treated 
OAE07 
Summary of Corneal Events by Preferred Term and Maximum Grade 
 
SAC [1] 
4.080 
All Treated 
OAE07 
Summary of Thrombocytopenia by Preferred Term and Maximum Grade 
 
SAC [1] 
4.090 
All Treated 
OAE07 
Summary of Infusion Related Reactions by Preferred Term and Maximum 
Grade 
 
SAC [1] 
4.100 
All Treated 
ESI2b 
Summary of Onset and Duration of the First Occurrence of Corneal Events 
 
SAC [1] 
4.110 
All Treated 
ESI1 
Summary of Characteristics of Corneal Events 
 
SAC [1] 
4.120 
All Treated 
ESI1 
Summary of Characteristics of Thrombocytopenia 
 
SAC [1] 
4.130 
All Treated 
AE3 
Summary of Corneal Events Leading to Dose Modification by Preferred Term 
 
SAC [1] 
Serious and Other Significant Adverse Events 
4.140 
All Treated 
AE3 
Summary of Serious Adverse Events by Preferred Term 
 
SAC [1] 
4.150 
All Treated 
AE3 
Summary of All Treatment-Related Serious Adverse Events by Preferred Term 
 
SAC [1] 


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Safety: Tables 
No. 
Population 
GSK Standard/ 
Example Shell 
Title  
Programming Notes Deliverable 
[Priority] 
4.160 
All Treated 
AE1 
Summary of Adverse Events Leading to Dose Modification by System Organ 
Class and Preferred Term 
 
SAC [1] 
Laboratory: Chemistry  
4.170 
All Treated 
OLB9B 
Summary of Chemistry Worst Grade Changes from Baseline Grade 
 
SAC [1] 
Laboratory: Hematology 
4.180 
All Treated 
OLB9B 
Summary of Hematology Worst Grade Changes from Baseline Grade 
 
SAC [1] 
Laboratory: Hepatobiliary (Liver) 
4.190 
All Treated  
LIVER10 
Summary of Hepatobiliary Laboratory Abnormalities 
 
SAC [1] 
ECG 
4.200 
All Treated 
EG1 
Summary of ECG Findings  
 
SAC [1] 
4.210 
All Treated 
OECG1B 
Summary of Worst-case Increases in Fridericia's QTc 
 
SAC [1] 
 


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14.12.11. Safety Figures 
No figures of safety data analysis. 


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Immunogenicity/Biomarker: Tables 
No. 
Population 
GSK Standard/ 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Immunogenicity 
5.010 
All Treated 
SAFE_T5 
Summary of Anti-Belantamab Mafodotin Antibodies (ADA) 
 
SAC [1] 

CCI


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14.12.13. Immunogenicity Figures 
No figures of immunogenicity. 
 
 


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14.12.14. Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Populatio
n 
GSK Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
PK Concentration Data 
6.010 
PK 
PK01 
Summary of Plasma Belantamab Mafodotin (ADC) PK 
Concentration-Time Data  
 
SAC [1] 
6.011 
PK 
PK01 
Summary of Plasma Belantamab Mafodotin (Total Antibody) PK 
Concentration-Time Data 
 
SAC [1] 
6.012 
PK 
PK01 
Summary of Plasma cys-mcMMAF PK Concentration-Time Data 
 
SAC [1] 
PK Parameter Data 
6.020 
PK 
PK06 
Summary of Derived Belantamab Mafodotin (ADC) PK Parameters PK06 with both transformed 
and untransformed values.  
SAC [1] 
6.021 
PK 
PK06 
Summary of Derived Belantamab Mafodotin (Total Antibody) PK 
Parameters 
PK06 with both transformed 
and untransformed values.  
SAC [1] 
6.022 
PK 
PK06 
Summary of Derived cys-mcMMAF PK Parameter 
PK06 with both transformed 
and untransformed values. 
SAC [1] 
Accumulation Ratio 
6.023 
PK 
PK05 
Summary of Results of Accumulation Ratio Assessment for 
Belantamab Mafodotin (ADC) 
Include Ro(CEOI) and 
Ro(Ctrough) with 95%CI in one 
table.  
SAC [1] 
6.024 
PK 
PK05 
Summary of Results of Accumulation Ratio Assessment for 
Belantamab Mafodotin (Total Antibody) 
Include Ro(CEOI) and 
Ro(Ctrough) with 95%CI in one 
table.  
SAC [1] 
6.025 
PK 
PK05 
Summary of Results of Accumulation Ratio Assessment for cys-
mcMMAF 
Include Ro(CEOI) and 
Ro(Ctrough) with 95%CI in one 
table.  
SAC [1] 
 


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14.12.15. Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
GSK Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
PK Concentration Data 
6.010 
PK 
PK16 
Individual Plasma Belantamab Mafodotin (ADC) Concentration-Time 
Plots (Linear and Semi-Log)  
 
SAC [1] 
6.011 
PK 
PK16 
Individual Plasma Belantamab Mafodotin (Total Antibody) Concentration-
Time Plots (Linear and Semi-Log)  
 
SAC [1] 
6.012 
PK 
PK16 
Individual Plasma cys-mcMMAF Concentration-Time Plots (Linear and 
Semi-Log) 
 
SAC [1] 
6.020 
PK 
PK17 
Mean Plasma Belantamab Mafodotin (ADC) Concentration-Time Plots 
(Linear and Semi-Log) 
 
SAC [1] 
6.021 
PK 
PK17 
Mean Plasma Belantamab Mafodotin (Total Anti-body) Concentration-
Time Plots (Linear and Semi-Log)  
 
SAC [1] 
6.022 
PK 
PK17 
Mean Plasma Belantamab Mafodotin (cys-mcMMAF) Concentration-Time 
Plots (Linear and Semi-Log)  
 
SAC [1] 
6.030 
PK 
PK18 
Median Plasma Belantamab Mafodotin (ADC) Concentration-Time Plots 
(Linear and Semi-Log) 
 
SAC [1] 
6.031 
PK 
PK18 
Median Plasma Belantamab Mafodotin (Total Anti-body) Concentration-
Time Plots (Linear and Semi-Log)  
 
SAC [1] 
6.032 
PK 
PK18 
Median Plasma Belantamab Mafodotin (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log)  
 
SAC [1] 
 
 
 
 


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14.12.16. Pharmacokinetic / Pharmacodynamic Tables 
No tables of Pharmacokinetic / Pharmacodynamic. 
 
 


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14.12.17. Pharmacokinetic / Pharmacodynamic Figures 
No figures of Pharmacokinetic / Pharmacodynamic. 
 
 
 


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14.12.20. ICH Listings 
ICH: Listings 
No. 
Population 
GSK Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.010 
All Treated 
ES2 
Listing of Reasons for Study Withdrawal 
 
SAC [1] 
1.020 
All Treated 
SD2 
Listing of Reasons for Study Treatment Discontinuation 
 
SAC [1] 
1.030 
All Treated 
CP_RA1p 
Listing of Planned and Actual Treatments 
 
SAC [1] 
Protocol Deviations 
1.040 
All Treated 
DV2 
Listing of Important Protocol Deviations  
 
SAC [1] 
1.050 
All Treated 
IE3 
Listing of Subjects with Inclusion/Exclusion Criteria Deviations 
 
SAC [1] 
Demographic and Baseline Characteristics 
1.060 
All Treated 
DM2 
Listing of Demographic Characteristics 
 
SAC [1] 
Prior and Concomitant Medications 
1.070 
All Treated 
CM3 
Listing of Prior and Concomitant Medications 
 
SAC [1] 
Exposure and Treatment Compliance 
1.080 
All Treated 
EX3 
Listing of Exposure Data 
 
SAC [1] 
1.090 
All Treated 
ODMOD10A 
Listing of Dose Reduction 
 
SAC [1] 
1.100 
All Treated 
ODMOD12A 
Listing of Dose Delays 
 
SAC [1] 
Response 
1.110 
All Treated 
Non- 
Listing of Investigator-Assessed Responses 
 
SAC [1] 
1.120 
All Treated 
TT9 
Listing of Duration of Response 
 
SAC [1] 
Adverse Events 
1.130 
All Treated 
AE8 
Listing of All Adverse Events 
 
SAC [1] 


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ICH: Listings 
No. 
Population 
GSK Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.140 
All Treated 
AE7 
Listing of Subject Numbers for Individual Adverse Events 
 
SAC [1] 
1.150 
All Treated 
AE2 
Listing of Relationship Between Adverse Event Preferred Term and 
Verbatim Text 
 
SAC [1] 
Serious and Other Significant Adverse Events 
1.160 
All Treated 
OAE4 
Listing of Adverse Events Leading to Permanent Discontinuation of 
Study Treatment  
 
SAC [1] 
1.170 
All Treated 
OAE4 
Listing of Adverse Events Leading to Dose Reduction of Study 
Treatment 
 
SAC [1] 
1.180 
All Treated 
OAE4 
Listing of Adverse Events Leading to Dose Interruptions of Study 
Treatment 
 
SAC [1] 
1.190 
All Treated 
OAE4 
Listing of Serious Adverse Events 
 
SAC [1] 
1.200 
All Treated 
OAE4 
Listing of Corneal Events 
 
SAC [1] 
1.210 
All Treated 
OAE4 
Listing of Thrombocytopenia 
 
SAC [1] 
All Laboratory 
1.220 
All Treated 
OLB13 
Listing of Laboratory Data with Character Results 
 
SAC [1] 
1.221 
All Treated 
LB5 
Listing of All Laboratory Data for Subjects with Any Value of 
Potential Clinical Importance 
 
SAC [1] 
ECOG 
1.230 
All Treated 
PS5A 
Listing of ECOG Performance Status 
 
SAC [1] 
PK 
1.240 
PK 
PK07 
Listing of Plasma Belantamab Mafodotin (ADC) Pharmacokinetic 
Concentration-Time Data 
 
SAC [1] 
1.250 
PK 
PK07 
Listing of Plasma Belantamab Mafodotin (Total Antibody) 
Pharmacokinetic Concentration-Time Data 
 
SAC [1] 


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ICH: Listings 
No. 
Population 
GSK Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.260 
PK 
PK07 
Listing of Plasma cys-mcMMAF Pharmacokinetic Concentration-
Time Data 
 
SAC [1] 
1.270 
PK 
PK03 
Listing of Derived Belantamab Mafodotin (ADC) PK Parameters 
(Untransformed) 
 
SAC [1] 
1.280 
PK 
PK03 
Listing of Derived Belantamab Mafodotin (Total Antibody) PK 
Parameters (Untransformed) 
 
SAC [1] 
1.290 
PK 
PK03 
Listing of Derived cys-mcMMAF PK Parameters (Untransformed) 
 
SAC [1] 
1.300 
PK 
PK15 
Listing of Belantamab Mafodotin (ADC) CEOI and Ctrough 
Accumulation Ratio 
 
SAC [1] 
1.310 
PK 
PK15 
Listing of Belantamab Mafodotin (Total Antibody) CEOI and Ctrough 
Accumulation Ratio 
 
SAC [1] 
1.320 
PK 
PK15 
Listing of cys-mcMMAF CEOI and Ctrough Accumulation Ratio 
 
SAC [1] 
 


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Non-ICH: Listings 
No. 
Population 
GSK Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
30.010 
Screened 
ES7 
Listing of Reasons for Screening Failure 
 
SAC [1] 
Medical Conditions 
30.020 
All Treated 
MH3 
Listing of Medical Conditions  
 
 
Anti-Cancer Therapy, Radiotherapy and Surgical Procedures
30.030 
All Treated 
AC6 
Listing of Prior Anti-Cancer Therapy  
 
SAC [1] 
Disease Characteristics 
30.040 
All Treated  
DC4 
Listing of Disease Characteristics  
 
SAC [1] 
ECG 
30.050 
All Treated 
OECG5A 
Listing of Fridericia's QTc Values of Potential Clinical Importance 
 
SAC [1] 
Vital Signs 
30.060 
All Treated 
VS4 
Listing of Vital Signs 

SAC [1] 
Anti-Drug Antibody 
30.070 
All Treated 
SAFE_L3  
Listing of Anti-Belantamab Mafodotin Antibody Results 

SAC [1] 
Genetic Characteristics  
30.090 
All Treated 
Non-Standard 
Listing of Genetic Characteristics 

SAC [1] 
Prior and Concomitant Medications 
CCI


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Non-ICH: Listings 
No. 
Population 
GSK Standard / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
30.100 
All Treated 
Non-Standard 
Listing of Blood Products 
 
SAC [1] 
30.110 
All Treated 
Non-Standard 
Listing of Blood Supportive Care Products 
 
SAC [1] 


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14.13. 
Appendix 13: Example Mock Shells for Data Displays 
The data display mock shells will be contained in separate documents which will be available on request.