Conditions: Multiple Myeloma
Keywords: Relapsed / Refractory Multiple Myeloma Antibody-Drug Conjugate belantamab mafodotin Combination therapy Belamaf
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 153
Healthy volunteers: no

Brief summary:
This study will evaluate the safety and tolerability profile of belantamab mafodotin when administered in combination with approved regimens of either Lenalidomide Plus Dexamethasone \[Len/Dex (Treatment A)\] or Bortezomib Plus Dexamethasone \[Bor/Dex (Treatment B)\] in participants with RRMM, i.e., those who have relapsed or who are refractory to at least 1 line of approved therapy.

Participants receiving treatment A, may continue combination treatment until the occurrence of progressive disease (PD), intolerable adverse events (AEs ), consent withdrawal, death or end of study. The participants receiving treatment B, may continue combination treatment for a total of up to 8 cycles. After 8 cycles of combination therapy, the participants will continue treatment with belantamab mafodotin, as a monotherapy until the occurrence of PD, intolerable AEs, consent withdrawal, death or end of study.

Detailed description:

Arms:
arm 1: Participants will receive SINGLE full dose of belantamab mafodotin as 2.5 mg/kg and 1.9 mg/kg on Day 1 of every 28-day cycle as a 30-60 min infusion.

SPLIT: belantamab mafodotin will be administered in two equal divided doses, 2.5 mg/kg SPLIT dose of a 1.25 mg/kg dose on Day 1 and a 1.25 mg/kg dose on Day 8 of each 28-day cycle.

STRETCH: belantamab mafodotin will be administered as 1.9 mg/kg dose on Day 1 of every alternate 28-day cycles (C1, C3, C5, C7 and so on.) Participants will also receive Lenalidomide 25 mg or 10 mg orally daily, on Days 1-21 of each 28 day cycle with Dexamethasone, 40 mg weekly per oral (PO)/intravenously (IV) on Days 1,8,15, \& 22 of each cycle. arm 2: Participants will receive SINGLE full dose of belantamab mafodotin as 3.4 mg/kg; 2.5 mg/kg; 1.9 mg/kg on Day 1 of each 21-day cycle. SPLIT: belantamab mafodotin will be administered in two equal divided doses: 3.4 mg/kg SPLIT as 1.7 mg/kg dose on Day 1 \& 1.7 mg/kg dose on Day 8; 2.5 mg/kg SPLIT dosing as 1.25 mg/kg dose on Day 1 \& 1.25 mg/kg dose on Day 8 of each 21-day cycle. STRETCH: belantamab mafodotin will be administered as single dose of 2.5 mg/kg on Day 1 of every alternate 21-day cycles (C1,C3,C5,C7 \& so on), 1.9 mg/kg administered on Day 1 of every alternate 21-day cycles (C1,C3,C5,C7 and so on). Step Down(S/D) STRETCH=belantamab mafodotin 2.5 mg/kg dose will be administered on Day 1 C1 followed by 1.9 mg/kg starting dose on Day1 of alternate 21-day cycles C3 onwards (C3,C5,C7, \& so on). Bortezomib will be administered at 1.3 mg/m\^2 SC/IV on Days 1,4,8, \& 11 of every 21-day cycle. Dex will be administered at 20 mg PO or IV on Days 1,2,4,5,8,9,11, \& 12 of every 21-day cycle.

Interventions: intervention 1: Belantamab mafodotin intervention 2: Lenalidomide intervention 3: Dexamethasone intervention 4: Bortezomib
Intervention descriptions: intervention 1: Selected doses of belantamab mafodotin will be administered as an infusion. intervention 2: Lenalidomide will be administered as 25 or 10 mg,orally, with belantamab mafodotin and dexamethasone. intervention 3: Dexamethasone will be administered as 20 or 40 mg, orally with belantamab mafodotin. intervention 4: Bortezomib will be administered as 1.3 mg/m\^2, as SC or IV, with belantamab mafodotin and dexamethasone.

Protocol document:
Prot_000.pdf: 
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TITLE PAGE 
Protocol Title: A Phase I/II, Open-label, Dose Escalation and Expansion Study to 
Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-Drug Conjugate 
GSK2857916 Administered in Combination with Lenalidomide Plus Dexamethasone 
(Arm A), or Bortezomib Plus Dexamethasone (Arm B) in Participants with 
Relapsed/Refractory Multiple Myeloma – (DREAMM 6) 
Protocol Number: 207497 / Amendment 04 
Compound Number: GSK2857916 
Brief Title: Phase I/II study of the Antibody-Drug Conjugate GSK2857916 
Administered in Combination with Lenalidomide Plus Dexamethasone (Arm A), or 
Bortezomib Plus Dexamethasone (Arm B) in Participants with Relapsed/Refractory 
Multiple Myeloma 
Study Phase: Phase 1/Phase 2 
Acronym: DREAMM 6 
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 can be found in the Study Reference 
Manual 
Sponsor Signatory: 
Timothy Crossman, BMBS MRes 
Group Sr. Director, Clinical Development Lead  
Approval Date: 30 Jun 2022 
Regulatory Agency Identifying Number(s): 
Registry 
ID 
IND number 
119333 
EudraCT number 
2017-004689-93 
©2022 GSK group of companies or its licensor. All rights reserved. Unauthorized 
copying or use of this information is prohibited.


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Document Identifier 
Amendment 4 
30 Jun 2022 
TMF-14624358 
Amendment 3 
13-Jul-2020 
2017N330850_04 
Amendment 2 
26-Apr-2019 
2017N330850_03 
Amendment 1 (Republished) 
14-May-2018 
2017N330850_02 
Amendment 1 
07-May-2018 
2017N330850_01 
Original Protocol 
28-Feb-2018 
2017N330850_00 
 
Amendment 04: 30 Jun 2022 
Overall Rationale for the Amendment:  
This protocol has been amended to update the end of study definition and to include 
continued access to study intervention (Post Analysis Continued Treatment [PACT]) after 
final analysis. 
Section # and Name Description of Change 
Brief Rationale  
Section 1 Synopsis 
Added additional content to implement 
post analysis continued treatment 
(PACT) phase and clarification of end 
of study definition  
To allow continued treatment of 
study participants who continue 
to derive clinical benefit post the 
final analysis   
Section 3 Schedule 
of Activities 
Added additional content to clarify visit 
schedule for PACT phase 
To allow continued treatment of 
study participants who continue 
to derive clinical benefit post 
final analysis 
Section 4.3.1 Risk 
Assessment 
Updated the summary of risk 
assessment table for the Combination 
Therapy of Belantamab Mafodotin with 
Len/Dex (Arm A) and Belantamab 
Mafodotin with Bor/Dex (Arm B) 
Changes made as per the latest 
IB 
Section 5 Objectives 
and Endpoints 
Included additional exploratory 
objectives  
To match plans for final 
statistical analysis 
Section 6.1 Overall 
Design 
Updated the language of the overall 
design section to differentiate between 
the end of data collection and the end 
of study timepoints 
To allow continued treatment of 
study participants who continue 
to derive clinical benefit post 
final analysis   


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Section # and Name Description of Change 
Brief Rationale  
Section 6.3 
Participant Study 
Completion, Study 
Analysis and End of 
Study 
Updated the language of study analysis 
section to combine the primary and 
final analysis 
Support deliverables for final 
CSR and to implement PACT 
Section 6.4 End of 
Study Definition 
Added additional content to implement 
PACT phase and end of study 
To allow continued treatment of 
study participants who continue 
to derive clinical benefit post 
final analysis 
Section 8.1.4 
Pharmaceutical 
Presentations 
Added additional content to dosage 
form of belantamab mafodotin as a 
lyophilized powder 
To allow continued treatment of 
study participants who continue 
to derive clinical benefit post 
final analysis 
Section 8.1.5 
Preparation of Doses 
Added additional content to preparation 
of belantamab mafodotin in lyophilized 
form 
To allow continued treatment of 
study participants who continue 
to derive clinical benefit post 
final analysis 
Section 8.8 
Treatment After the 
End of the Study 
Clarification around treatment following 
end of the study 
To allow continued treatment of 
study participants who continue 
to derive clinical benefit post 
final analysis 
Section 8.9 
Continued Access to 
Study Intervention 
after Final Data Cut 
New section to align with 
implementation of PACT phase 
To allow continued treatment of 
study participants who continue 
to derive clinical benefit post 
final analysis   
Section 10.2.1 Time 
Period and 
Frequency for 
Collecting AE and 
SAE Information  
Included additional content to align with 
implementation of PACT phase 
To allow continued treatment of 
study participants who continue 
to derive clinical benefit post 
final analysis   
Section 12.4.9 Final 
Analysis 
Updated the language of study analysis 
section to combine the primary and 
final analysis 
Support deliverables for final 
CSR and to implement PACT 
 
 


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TABLE OF CONTENTS 
PAGE 
1. 
SYNOPSIS ............................................................................................................. 10 
2. 
STUDY SCHEMA ................................................................................................... 25 
3. 
SCHEDULE OF ACTIVITIES ................................................................................. 27 
4. 
INTRODUCTION .................................................................................................... 82 
4.1. 
Study Rationale .......................................................................................... 82 
4.2. 
Background ................................................................................................ 83 
4.2.1. 
Current Treatment of Multiple Myeloma ....................................... 83 
4.2.2. 
Role of B-Cell Maturation Antigen in Multiple Myeloma ................ 84 
4.2.3. 
Antibody-Drug Conjugate Belantamab Mafodotin ........................ 84 
4.2.4. 
Clinical Experience with Belantamab Mafodotin ........................... 85 
4.2.4.1. 
Clinical activity in studies with belantamab 
mafodotin monotherapy .............................................. 85 
4.2.4.2. 
Clinical Safety in belantamab mafodotin 
monotherapy studies .................................................. 86 
4.2.4.3. 
Pharmacokinetics and Pharmacodynamic in 
Humans ...................................................................... 88 
4.2.4.4. 
Clinical Summary ....................................................... 89 
4.3. 
Benefit/Risk Assessment ............................................................................ 89 
4.3.1. 
Risk Assessment ......................................................................... 89 
4.3.2. 
Benefit Assessment ..................................................................... 93 
4.3.3. 
Overall Benefit:Risk Conclusion ................................................... 93 
5. 
OBJECTIVES AND ENDPOINTS ........................................................................... 93 
6. 
STUDY DESIGN .................................................................................................... 97 
6.1. 
Overall Design ............................................................................................ 97 
6.1.1. 
Arm A - Belantamab Mafodotin with Len/Dex ............................... 98 
6.1.1.1. 
Part 1 Dose Escalation Phase .................................... 98 
6.1.1.2. 
Dose Escalation Decisions ....................................... 103 
6.1.1.3. 
Part 2 Dose Expansion ............................................. 103 
6.1.2. 
Arm B - Belantamab Mafodotin with Bor/Dex ............................. 104 
6.1.2.1. 
Part 1 Dose Escalation Phase .................................. 104 
6.1.2.2. 
Dose Escalation Decisions ....................................... 105 
6.1.2.3. 
Part 2 Dose Expansion ............................................. 106 
6.1.3. 
Criteria for Belantamab Mafodotin DLT in Part 1 ........................ 107 
6.2. 
Number of Participants ............................................................................. 109 
6.3. 
Participant Study Completion, Study Analysis and End of Study ............... 109 
6.4. 
End of Study Definition ............................................................................. 109 
6.5. 
Scientific Rationale for Study Design ........................................................ 110 
6.6. 
Dose Justification ...................................................................................... 111 
6.6.1. 
Starting Dose of Belantamab Mafodotin ..................................... 111 
6.6.2. 
Alternate Schedule for Belantamab Mafodotin ........................... 112 
6.6.3. 
Standard of Care Dosing ........................................................... 112 
6.6.3.1. 
Len/Dex Dose (Arm A) ............................................. 112 
6.6.3.2. 
Bor/Dex Dose (Arm B) .............................................. 112 


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7. 
STUDY POPULATION ......................................................................................... 113 
7.1. 
Inclusion Criteria ....................................................................................... 113 
7.2. 
Exclusion Criteria ...................................................................................... 116 
7.3. 
Lifestyle Restrictions ................................................................................. 118 
7.4. 
Screen Failures......................................................................................... 119 
8. 
TREATMENTS ..................................................................................................... 119 
8.1. 
Treatments Administered .......................................................................... 119 
8.1.1. 
Belantamab Mafodotin and Len/Dex Combination (Arm A) 
28-day Cycle: SINGLE,SPLIT, and STRETCH Schedules ......... 121 
8.1.1.1. 
Belantamab mafodotin .............................................. 122 
8.1.1.2. 
Len/Dex .................................................................... 122 
8.1.2. 
Belantamab Mafodotin and Bor/Dex Combination (Arm B) 
21-day Cycle: SINGLE and SPLIT Schedules ............................ 123 
8.1.2.1. 
Belantamab Mafodotin .............................................. 124 
8.1.2.2. 
Bor/Dex .................................................................... 125 
8.1.3. 
Belantamab Mafodotin and Bor/Dex Combination (Arm B) 
21-day Cycle: STRETCH and S/D STRETCH Dosing 
Schedule.................................................................................... 125 
8.1.3.1. 
Belantamab mafodotin .............................................. 126 
8.1.3.2. 
Bor/Dex .................................................................... 126 
8.1.4. 
Pharmaceutical Presentation ..................................................... 127 
8.1.4.1. 
Belantamab mafodotin .............................................. 127 
8.1.4.2. 
Lenalidomide ............................................................ 127 
8.1.4.3. 
Bortezomib ............................................................... 127 
8.1.4.4. 
Dexamethasone ....................................................... 128 
8.1.5. 
Preparation of Doses ................................................................. 131 
8.1.5.1. 
Belantamab mafodotin .............................................. 131 
8.1.5.2. 
Lenalidomide ............................................................ 131 
8.1.5.3. 
Bortezomib ............................................................... 131 
8.1.5.4. 
Dexamethasone ....................................................... 132 
8.1.6. 
Treatment Duration .................................................................... 132 
8.1.6.1. 
Arm A ....................................................................... 132 
8.1.6.2. 
Arm B ....................................................................... 132 
8.1.6.3. 
Lack of tolerability in Arm A or B ............................... 132 
8.2. 
Dose Modification ..................................................................................... 132 
8.2.1. 
Dose Modification After Cycle 1 ................................................. 132 
8.2.2. 
Dose Modification Guidelines for Dexamethasone ..................... 144 
8.3. 
Method of Treatment Assignment ............................................................. 145 
8.4. 
Blinding ..................................................................................................... 145 
8.5. 
Preparation/Handling/Storage/Accountability ............................................ 145 
8.6. 
Treatment Compliance .............................................................................. 146 
8.7. 
Concomitant Therapy................................................................................ 146 
8.7.1. 
Permitted Concomitant Medications and Therapies ................... 146 
8.7.2. 
Prohibited Concomitant Medications and Therapies .................. 147 
8.7.3. 
Prohibited Devices ..................................................................... 147 
8.8. 
Treatment After the End of the Study ........................................................ 147 
8.9. 
Continued Access to Study Intervention after Final Data cut ..................... 148 
9. 
DISCONTINUATION CRITERIA ........................................................................... 148 
9.1. 
Discontinuation of Study Treatment .......................................................... 148 


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9.1.1. 
Discontinuation of Individual Components of Combination 
Study Treatment ........................................................................ 149 
9.2. 
Safety Stopping Criteria ............................................................................ 149 
9.2.1. 
Liver Chemistry Stopping Criteria .............................................. 149 
9.2.2. 
Study Treatment Restart or Rechallenge ................................... 150 
9.2.3. 
QTc Interval Stopping Criteria .................................................... 150 
9.2.4. 
Left Ventricular Ejection Fraction (LVEF) Stopping Criteria ........ 151 
9.2.5. 
Corneal Event Stopping Criteria ................................................. 152 
9.2.6. 
Infusion-Related Reaction Management and Stopping 
Criteria ....................................................................................... 152 
9.2.7. 
Allergic and Anaphylactic Reaction Stopping Criteria ................. 152 
9.3. 
Withdrawal from the Study ........................................................................ 152 
9.4. 
Lost to Follow-Up ...................................................................................... 153 
10. STUDY ASSESSMENTS AND PROCEDURES ................................................... 154 
10.1. 
Assessments for Evaluation of Clinical Activity ......................................... 154 
10.1.1. 
Imaging ...................................................................................... 154 
10.2. 
Adverse Events......................................................................................... 155 
10.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................. 155 
10.2.2. 
Method of Detecting AEs and SAEs ........................................... 156 
10.2.3. 
Follow-up of AEs and SAEs ....................................................... 156 
10.2.4. 
Regulatory Reporting Requirements for SAEs ........................... 157 
10.2.5. 
Cardiovascular and Death Events .............................................. 157 
10.2.6. 
Adverse Events of Special Interest ............................................ 157 
10.2.7. 
Pregnancy ................................................................................. 158 
10.2.8. 
Medical Device Incidents (including malfunctions) ..................... 158 
10.3. 
Treatment of Overdose ............................................................................. 158 
10.3.1. 
Belantamab Mafodotin Overdose ............................................... 158 
10.3.2. 
Lenalidomide Overdose ............................................................. 159 
10.3.3. 
Bortezomib Overdose ................................................................ 159 
10.3.4. 
Dexamethasone Overdose ........................................................ 159 
10.4. 
Demographics and Medical History........................................................... 159 
10.5. 
Daily Study Diary ...................................................................................... 160 
10.6. 
Safety Assessments ................................................................................. 160 
10.6.1. 
Physical Examinations ............................................................... 160 
10.6.2. 
ECOG Performance Status ........................................................ 160 
10.6.3. 
Vital Signs .................................................................................. 160 
10.6.4. 
New York Heart Association Functional Scale ........................... 161 
10.6.5. 
Electrocardiograms .................................................................... 161 
10.6.6. 
Echocardiogram......................................................................... 161 
10.6.7. 
Ophthalmic Examinations .......................................................... 161 
10.6.7.1. Ocular Examinations and Procedures....................... 163 
10.6.8. 
Patient-Reported Outcome Version of the Common Term 
Criteria for Adverse Events (PRO-CTCAE) ................................ 163 
10.6.9. 
Visual Function Safety Assessment ........................................... 164 
10.6.9.1. National Eye Institute Visual Function 
Questionnaire-25 ...................................................... 164 
10.6.9.2. The Ocular Surface Disease Index ........................... 164 
10.6.10. Laboratory Assessments ........................................................... 165 
10.6.11. DNA Sampling for Genetic Testing ............................................ 166 
10.6.12. Suicidal Risk Monitoring ............................................................. 167 


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10.7. 
Pharmacokinetics ..................................................................................... 167 
10.7.1. 
Blood Sample Collection for Pharmacokinetics .......................... 167 
10.7.2. 
Pharmacokinetic Sample Analysis ............................................. 168 
10.9. 
Immunogenicity Assessments ................................................................... 170 
 
10.11. Health-Related Quality of Life ................................................................... 171 
10.11.1. European Organisation for Research and Treatment of 
Cancer Quality of Life Questionnaires ........................................ 171 
10.11.1.1. European Organisation for Research and 
Treatment of Cancer Quality of Life 
Questionnaire 30-item Core Module (EORTC 
QLQ-C30) ................................................................. 172 
10.11.1.2. European Organisation for Research and 
Treatment of Cancer Quality of Life 
Questionnaire 20-item Multiple Myeloma 
Module (EORTC QLQ-MY20) ................................... 172 
11. DATA MANAGEMENT ......................................................................................... 172 
12. STATISTICAL CONSIDERATIONS ...................................................................... 173 
12.1. 
Hypothesis(es) .......................................................................................... 173 
12.1.1. 
Arm A – Belantamab Mafodotin with Len/Dex ............................ 173 
12.1.1.1. Part 1 ....................................................................... 173 
12.1.1.2. Part 2 ....................................................................... 173 
12.1.2. 
Arm B – Belantamab Mafodotin with Bor/Dex ............................ 173 
12.1.2.1. Part 1 ....................................................................... 173 
12.1.2.2. Part 2 ....................................................................... 174 
12.2. 
Sample Size Determination ...................................................................... 174 
12.2.1. 
Arm A – Belantamab Mafodotin with Len/Dex ............................ 174 
12.2.1.1. Part 1 ....................................................................... 174 
12.2.1.2. Part 2 ....................................................................... 174 
12.2.2. 
Arm B – Belantamab Mafodotin with Bor/Dex ............................ 174 
12.2.2.1. Part 1 ....................................................................... 174 
12.2.2.2. Part 2 ....................................................................... 175 
12.2.3. 
Sample Size Sensitivity .............................................................. 175 
12.2.4. 
Sample Size Re-estimation or Adjustment ................................. 175 
12.3. 
Populations for Analyses .......................................................................... 175 
12.4. 
Statistical Analyses ................................................................................... 175 
12.4.1. 
Analyses of Clinical Activity ....................................................... 176 
12.4.2. 
Safety Analyses ......................................................................... 176 
12.4.2.1. Exposure Duration .................................................... 176 
12.4.2.2. Adverse Events ........................................................ 176 
12.4.2.3. Clinical Laboratory Evaluations ................................ 177 
12.4.2.4. Other Safety Measures ............................................. 177 
12.4.3. 
Pharmacokinetic Analyses ......................................................... 177 
12.4.3.1. Belantamab mafodotin pharmacokinetic ................... 177 
CCI
CCI


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12.4.3.2. Lenalidomide ............................................................ 178 
12.4.3.3. Bortezomib ............................................................... 178 
12.4.4. 
Pharmacokinetic/PD Analyses ................................................... 178 
12.4.5. 
Translational Research Analyses ............................................... 179 
12.4.5.1. Novel Biomarker(s) Analyses ................................... 179 
12.4.5.2. Genetic Analyses ..................................................... 179 
12.4.6. 
Immunogenicity Assessment ..................................................... 179 
12.4.7. 
Other Analyses .......................................................................... 180 
12.4.8. 
Interim Analyses ........................................................................ 180 
12.4.8.1. Arm A – belantamab mafodotin with Len/Dex ........... 180 
12.4.8.2. Arm B – belantamab mafodotin with Bor/Dex ........... 181 
12.4.9. 
Final Analysis ............................................................................ 181 
13. REFERENCES ..................................................................................................... 182 
14. APPENDICES ...................................................................................................... 187 
14.1. 
Appendix 1: Abbreviations and Trademarks .............................................. 187 
14.1.1. 
Trademark Information ............................................................... 187 
14.1.2. 
Abbreviations and Acronyms ..................................................... 187 
14.2. 
Appendix 2:  Study Governance Considerations and Informed 
Consent Process ...................................................................................... 191 
14.3. 
Appendix 3: Eastern Cooperative Oncology Group (ECOG) 
Functional Status ...................................................................................... 195 
14.4. 
Appendix 4:  Modified Diet in Renal Disease (MDRD) Formula ................. 196 
14.5. 
Appendix 5: New York Heart Association Classification ............................ 197 
14.6. 
Appendix 6: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ..................................... 198 
14.7. 
Appendix 7: Contraceptive Guidance and Collection of Pregnancy 
Information ................................................................................................ 205 
14.8. 
Appendix 8: Corneal Event Grading and Mitigation Strategy ..................... 208 
14.9. 
Appendix 9: Liver Safety: Required Actions, Follow-up 
Assessments, and Study Treatment Rechallenge Guidelines ................... 212 
14.9.1. 
Liver Safety Drug Restart or Re-Challenge Guidelines .............. 214 
14.9.1.1. Rechallenge Following Liver Stopping Events 
that are Possibly Related to Study Treatment ........... 214 
14.9.1.2. Restart Following Transient Resolving Liver 
Stopping Events NOT Related to Study 
Treatment ................................................................. 216 
14.9.1.3. References: .............................................................. 217 
14.10. Appendix 10:  Genetics ............................................................................. 218 
 
14.10.2. Study Population ........................................................................ 219 
14.10.3. Study Assessments and Procedures ......................................... 219 
14.10.4. Informed Consent ...................................................................... 220 
14.10.5. Participant Withdrawal from Study ............................................. 220 
14.10.6. Screen and Baseline Failures .................................................... 220 
14.10.7. Provision of Study Results and Confidentiality of 
Participant’s Genetic Data ......................................................... 220 
14.10.8. Germline Control ........................................................................ 221 
CCI
CCI


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14.10.9. References ................................................................................ 221 
14.11. Appendix 11: Operating Characteristics of Safety Stopping Rule for 
Expansion Cohort ..................................................................................... 222 
14.12. Appendix 12: Eye care specialist’s qualifications and requirements .......... 223 
14.13. Appendix 13: Alternative Health Care Approaches ................................... 224 
14.14. Appendix 14: Protocol Amendment History ............................................... 226 
14.14.1. Protocol Amendment 3 (13-Jul-2020) ........................................ 226 
14.14.2. Protocol Amendment 2 (26-APR-2019) from the Final 
Version (28-FEB-2018) .............................................................. 234 
14.14.3. Protocol Amendment 1 (7-MAY-2018): ...................................... 245 
 


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1. 
SYNOPSIS 
Protocol Title: A Phase I/II, Open-label, Dose Escalation and Expansion Study to 
Evaluate Safety, Tolerability, and Clinical Activity of the Antibody-Drug Conjugate 
GSK2857916 Administered in Combination with Lenalidomide Plus Dexamethasone 
(Treatment Arm A), or Bortezomib Plus Dexamethasone (Treatment Arm B) in 
Participants with Relapsed or Refractory Multiple Myeloma – DREAMM 6. 
Short Title:  Dose Escalation/Dose Expansion Study of GSK2857916 Administered with 
Lenalidomide Plus Dexamethasone (Arm A), or Bortezomib Plus Dexamethasone (Arm 
B) in Participants with RRMM. 
Brief Rationale 
Belantamab mafodotin is a humanized IgG1 antibody drug conjugate (ADC) which binds 
specifically to B-cell maturation antigen (BCMA) (Figure 3) [Tai, 2014; Montes De Oca, 
2019].  Upon binding to the cell surface, belantamab mafodotin is rapidly internalized 
and active drug (cysteine monomethyl auristatin F [cys-mcMMAF]) is released inside the 
cell.  Belantamab mafodotin has been produced in an afucosylated form to generate an 
enhanced ADCC/ADCP response upon binding to FcRIIIa receptors on the surface of 
human effector cells.  Importantly, BCMA expression is maintained at the cell surface 
over time following belantamab mafodotin binding and internalization due to rapid 
BCMA receptor recycling and/or new protein synthesis. 
We hypothesize that the combination of belantamab mafodotin with standard of care 
(SoC) therapies (lenalidomide/dexamethasone [Len/Dex] or bortezomib/dexamethasone 
[Bor/Dex]) may potentially result in additive or enhanced effects and could potentially 
translate into deeper and longer responses for relapsed/refractory multiple myeloma 
(RRMM) participants treated with either Len/Dex or Bor/Dex alone. While there are 
some potential overlaps in the pattern of identified toxicities (primarily hematologic), 
they are expected to be manageable. Given the single agent activity of belantamab 
mafodotin in RRMM, the combination therapy with these agents remains an attractive 
option to explore for RRMM.  
This study will evaluate the safety and tolerability profile of belantamab mafodotin when 
administered in combination with approved SoC regimens of either Len/Dex (Arm A) or 
Bor/Dex (Arm B) in participants with RRMM, i.e., those who have relapsed or who are 
refractory to at least 1 line of approved therapy. Part 1 of the study is a dose escalation 
phase to evaluate the safety and tolerability of up to 3 dose levels and up to 2 dosing 
schedules of belantamab mafodotin in combination with the two SoC regimens. Part 2 
will further evaluate the safety and preliminary clinical activity of belantamab mafodotin 
at selected dose levels and alternate dosing schedules in combination with Len/Dex or 
Bor/Dex. 
Overall Objectives and Endpoints 
The primary and secondary objectives, along with the corresponding endpoints for study 
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Objectives 
Endpoints 
Primary 
Dose Escalation 
Determine safety, tolerability of 
belantamab mafodotin in combination with 
either Len/Dex (Arm A) or Bor/Dex (Arm 
B) to establish a recommended dose 
range and schedule to evaluate in Dose 
Expansion for participants with RRMM 
 
Dose Escalation and Expansiona 
Select the dose(s) and dosing schedule for 
further investigation based on safety and 
tolerability of belantamab mafodotin in 
combination with either Len/Dex (Arm A) 
or Bor/Dex (Arm B) for participants with 
RRMM     
 
Number (%) of participants with dose-limiting 
toxicities (DLTs). 
Number (%) of participants with adverse events 
(AEs), changes in clinical signs and laboratory 
parameters. 
 
 
A comprehensive determination based on 
safety and serious adverse events (SAEs)/AEs.  
Dose Expansion 
To determine preliminary clinical activity of 
belantamab mafodotin in combination with 
either Len/Dex (Arm A) or Bor/Dex (Arm 
B) for participants with RRMM     
 
A specific determination based on ORR defined 
as percentage (%) of participants achieving 
PR as defined by the IMWG Uniform 
Response Criteria for MM [Kumar, 2016]. 
Secondary 
Dose Escalation and Expansion 
To evaluate the pharmacokinetics profile 
of belantamab mafodotin when 
administered in combination with Len/Dex 
(Arm A) or Bor/Dex (Arm B) in participants 
with RRMM 
Belantamab mafodotin PK parameters, as data 
permit  
To evaluate the pharmacokinetics profile 
of lenalidomide when administered in 
combination with belantamab mafodotin 
and dexamethasone 
Lenalidomide PK parameters, as data permit in 
Cycle 1 
To evaluate the pharmacokinetics profile 
of bortezomib when administered in 
combination with belantamab mafodotin 
and dexamethasone 
Bortezomib PK parameters, as data permit in 
Cycle 1 
To assess anti-drug antibodies (ADAs) 
against belantamab mafodotin 
Incidence and titers of ADAs against 
belantamab mafodotin pre-dose in Cycle 1 and 
selected subsequent cycles 
To evaluate the effect and tolerability of 
belantamab mafodotin in combination with 
Len/Dex (Arm A) or Bor/Dex (Arm B) on 
Changes from baseline in symptoms and 
related impacts as measured by OSDI, NEI-
VFQ-25 and PRO CTCAE 


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Objectives 
Endpoints 
symptomatic adverse events in 
participants with RRMM 
To further characterize safety of 
belantamab mafodotin administered in 
combination with Len/Dex (Arm A) or 
Bor/Dex (Arm B) in participants with 
RRMM 
Incidence of AEs, including SAEs and AEs of 
special interest (corneal events, 
thrombocytopenia and infusion related 
reactions). 
 
Ocular findings on ophthalmic exam 
To evaluate the effect of belantamab 
mafodotin in combination with Len/Dex 
(Arm A) or Bor/Dex (Arm B) on health-
related quality of life in participants with 
RRMM 
Changes from baseline in health-related quality 
of life as measured by the EORTC QLQ-C30 
and QLQ-MY20 
a. 
Data from the both the Escalation and Expansion cohorts will be used to evaluate this composite endpoint. 
 
Overall Study Design 
This is a Phase I/II, open-label, dose escalation and expansion study to select the dose 
and dosing schedule of belantamab mafodotin when given in combination with Len/Dex 
(Arm A) on a 28-day cycle, or with Bor/Dex (Arm B) on a 21-day cycle, and to evaluate 
safety and clinical activity of the combination treatments in participants with RRMM. 
The study will consist of two parts.  
Part 1 is a dose escalation phase to evaluate the safety and tolerability of belantamab 
mafodotin in combination with two SoC regimens: Arm A – belantamab mafodotin with 
Len/Dex, and Arm B – belantamab mafodotin with Bor/Dex. 
Part 2 is a dose expansion phase to further evaluate the safety and clinical activity of 
belantamab mafodotin in combination with Len/Dex (Arm A) and Bor/Dex (Arm B). 
The overall study design is summarized in Schematic of Study Structure figures (Figure 1 
and Figure 2). 
Dosing Schedules 
SINGLE Dosing Schedule (both Arm A and Arm B): belantamab mafodotin will be 
administered as a SINGLE full dose on Day 1 of each 28-day (Arm A) or 21-day (Arm 
B) cycle.   
SPLIT Dosing Schedule (both Arm A and Arm B): belantamab mafodotin will be split 
into two equal halves and each half dose will be administered on Day 1 and Day 8 of 
each 28-day (Arm A) or 21-day (Arm B) cycle. 


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In protocol amendment 3, the following new schedules are being introduced to evaluate 
the safety and clinical activity of belantamab mafodotin with Len/Dex (Arm A) or Bor/ 
Dex (Arm B): 
Arm A only: 
• STRETCH Dosing Schedule: A STRETCH dosing schedule for the 1.9 mg/kg 
dose level might be considered for Arm A if emerging data suggests that this 
schedule may further optimize the tolerability or offers an improved benefit/risk 
profile. In STRETCH schedule, belantamab mafodotin will be administered on 
Day 1 of alternate 28-day cycles with any 2 consecutive planned belantamab 
mafodotin doses at least 56 (3) days apart. The treatment cycle duration will 
remain at 28 days (4 weeks). 
Arm B only: 
• STRETCH Dosing Schedule: belantamab mafodotin will be administered on Day 
1 of alternate cycles with any two consecutive planned doses at least 42 (3) days 
apart. The treatment cycle duration will remain at 21 days (3 weeks). 
• Step-Down (S/D) STRETCH Dosing Schedule: belantamab mafodotin will be 
administered as a full 2.5 mg/kg dose on Day 1 of Cycle 1 followed by 
subsequent planned doses of 1.9 mg/kg S/D dose starting on Day 1 of alternate 
21-day cycles (C3, C5, C7, and so on) with any two consecutive planned doses at 
least 42 (3) days apart. The treatment cycle duration will remain at 21 days 
(3 weeks). 
Number of Participants 
Overall, it is estimated that approximately 152 treated participants will be enrolled in this 
two-part study; approximately 27 participants in Part 1 and approximately 125 
participants in Part 2. 
• 
Part 1 (dose escalation phase): Up to 27 DLT-evaluable participants with RRMM 
(approximately 14 participants in Arm A and approximately 13 participants in Arm 
B) will be evaluated. 
• 
Part 2 (dose expansion phase): Approximately 125 participants with RRMM 
(approximately 31 participants in Arm A and approximately 94 participants in Arm 
B will be evaluated to further assess the safety and preliminary clinical activity of the 
combination treatments. 
At the time of Amendment 3 more participants have been added to Part 1 (both Arm A 
and Arm B) for the study due to non-DLT evaluable participants and the requirement for 
an additional replacement participant to assure an adequate assessment of DLTs. Two 
participants were added to Part 2 (Arm A and Arm B) as a replacement for participants 
who either received an incorrect dose or failed to complete a full cycle. 
 


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Arm A – Belantamab mafodotin in combination with Len/Dex 
Part 1: Dose Escalation 
The modified Toxicity Probability Interval (mTPI) design [Ji, 2010] will be used to guide 
dose escalation in Part 1 with a slight modification (Figure 1). Up to 2 dose levels of 
belantamab mafodotin (1.9 mg/kg [dose level -1]; 2.5 mg/kg [dose level 1] and 
alternative dosing schedules are planned to be evaluated in combination with the fixed 
dose of the Len/Dex treatments. Based on emerging data from Arm A, the first dose 
investigated in Protocol Amendment 2 was 1.9 mg/kg (Dose Level -1). The design 
assumes the true underlying toxicity rate for maximum tolerated dose (MTD) of 
belantamab mafodotin falls within the range from 25% to 35% and centers at 30%. 
Cohorts will be recruited in blocks of 3 participants. Participants will be treated in a 
staggered approach with at least 1 day between each participant’s first dose of 
belantamab mafodotin to minimize the risk of inadvertently exceeding the MTD in 
multiple participants.  
Up to 2 dose levels of belantamab mafodotin will be evaluated starting with 1.9 mg/kg. 
Data from at least 3 DLT-evaluable participants are required before a decision is made to 
escalate to the next dose level.  
Part 2: Dose Expansion 
Data from at least 3 DLT-evaluable participants are not required for enrollment of more 
participants at the same dose level in Part 2.  
Once Part 2 expansion is open for each dosing schedule, up to 12 participants will be 
enrolled in each cohort, unless enrollment is stopped based on emerging data.  
Since the implementation of amendment 2, Part 1 has been completed and Part 2 has 
since been enrolling participants to further evaluate the safety profile and to evaluate the 
preliminary clinical activity of belantamab mafodotin in combination with Len/Dex at the 
2.5 mg/kg dose level with 2 dosing schedules (2.5 mg/kg SINGLE and 2.5 mg/kg 
SPLIT). 
In Amendment 3, in Part 2, an alternate dosing schedule of STRETCH (Q8W) dosing 
may be explored for the 1.9 mg/kg dose level if emerging data (from either this study or 
across the program) suggests that this schedule may further optimize the tolerability or 
offers an improved benefit/risk profile. To enable this, a potential extended dosing 
schedule has been introduced via amendment 3, where belantamab mafodotin at 1.9 
mg/kg will be administered once every 8 weeks (STRETCH) and will be evaluated 
dependent on emerging data. The cycle duration will remain 28 days/4 weeks. Up to 12 
participants will be enrolled in this new cohort. 
Safety data from all enrolled participants will be closely monitored while the study is 
ongoing. The observed number of participants permanently discontinuing study treatment 
within the first two cycles due to AEs related to belantamab mafodotin will be compared 
against defined safety stopping rules. Enrollment may stop for a given dose level/dosing 
schedule if the safety stopping rules are met. 


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Arm B – Belantamab mafodotin in combination with Bor/Dex 
Part 1: Dose Escalation 
A mTPI design will be implemented [Ji, 2010] to guide dose escalation in Part 1 (Figure 
2). Up to 2 dose levels of belantamab mafodotin (2.5 mg/kg [dose level 1]; 3.4 mg/kg 
[dose level 1]; 1.9 mg/kg [dose level +1]), starting with 2.5 mg/kg, are planned to be 
evaluated in combination with a fixed dose of Bor/Dex. Cohorts will be recruited in 
blocks of 3 participants. Participants will be entered in a staggered approach with at least 
1 day between each participant’s first dose of belantamab mafodotin to minimize the risk 
of inadvertently exceeding the MTD in multiple participants. A maximum of 6 
participants will be assigned to each dose. 
Evaluation of the available safety data over the first cycle of treatment for each 
participant enrolled in that dose level is required from at least 3 participants before a 
decision is made to enroll additional participants at the same or the subsequent dose level. 
Part 2: Dose Expansion  
Part 2 is a dose expansion phase to further evaluate the safety and clinical activity of 
belantamab mafodotin in combination with Bor/Dex. 
Since the implementation of amendment 2, Part 2 has been enrolling in multiple 
expansion cohorts to further evaluate the safety profile and to evaluate the preliminary 
clinical activity of belantamab mafodotin in combination with Bor/Dex at 2 dose levels 
and alternate dosing schedules (2.5 mg/kg SPLIT, 2.5 mg/kg SINGLE, 3.4 mg/kg SPLIT, 
3.4 mg/kg SINGLE). Enrollment of each cohort was conducted in blocks of 3 participants 
until 12 participants each at 2.5 mg/kg SPLIT, 2.5 mg/kg SINGLE, 3.4 mg/kg SPLIT and 
up to 9 participants at 3.4 mg/kg SINGLE were enrolled. 
In Amendment 3, four new cohorts are being introduced (1.9 mg/kg SINGLE, 2.5 mg/kg 
STRETCH, S/D STRETCH and 1.9 mg/kg STRETCH). Enrollment for each cohort will 
be conducted in blocks of 3 participants until up to 12 participants are enrolled in each of 
the 4 new dosing cohorts.  
Safety data from all enrolled participants will be closely monitored while the study is 
ongoing. The observed number of participants permanently discontinuing study treatment 
within the first two cycles due to AEs related to belantamab mafodotin will be compared 
against defined safety stopping rules. Enrollment may stop for a given dose level and 
higher dose level(s) if the safety stopping rules are met. 
Treatment Groups and Treatment Duration 
Arm A – Belantamab mafodotin in combination with Len/Dex 
In Arm A, belantamab mafodotin is given in up to 2 dose levels and up to 3 dosing 
schedules in combination with Len/Dex on a 28-day cycle (Table 1).  


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Table 1 
Arm A Dosing Regimens 
Arm A 
Part 
Dose 
Level 
Cohort  
Dose of 
Belantamab 
Mafodotin 
Schedule of 
Belantamab 
Mafodotin 
SoA  
Len/Dex 
treatment 
28-day 
Cycle 
1 
-1 
1.9 mg/kg 
SINGLE 
 1.9 mg/kg IV  
Day 1 of every 
28-day cycle 
Table 5 
Lenalidomide 
25mg PO QD, 
D1-D21; 
Dexamethasone 
20mg PO or IV 
on D1, 8, 15, 22 
2 
 
1.9 mg/kg 
STRETCH 
Day 1 of alternate 
28-day cycles 
(i.e. C1, C3, C5, 
C7 and so on) 
1 and 
2 
1 
2.5 mg/kg 
SINGLE 
 2.5 mg/kg IV  
Day 1 
Table 5 
2.5 mg/kg 
SPLIT 
 1.25 mg/kg IV  
Day 1 and Day 8 
Table 6 
 
For SINGLE dosing schedule, belantamab mafodotin will be administered FIRST (prior 
to Len/Dex) as a single full dose on Day 1 (D1) of every 28-day cycle as a 30-60 min 
infusion, followed by a 1 to 2 h rest period.   
• 2.5 mg/kg SINGLE dosing schedule will administer a 2.5 mg/kg dose on Day 1 of 
each 28-day cycle  
• 1.9 mg/kg SINGLE dosing schedule will administer a 1.9 mg/kg dose on Day 1 of 
each 28-day cycle 
For SPLIT dosing schedule, belantamab mafodotin will be administered FIRST (prior 
to Len/Dex) in the clinic in two equal divided doses - one on Day 1 and the other on Day 
8 of each 28-day cycle as a 30-60 min infusion, followed by a 1 to 2 h rest period.  
• 2.5 mg/kg SPLIT dosing schedule will administer a 1.25 mg/kg dose on Day 1 
and a 1.25 mg/kg dose on Day 8 of each 28-day cycle  
For STRETCH dosing schedule, belantamab mafodotin will be administered FIRST 
(prior to Len/Dex) as a single dose on Day 1 of every alternate 28-day cycle as a 30-60 
min infusion, followed by 1 to 2 h rest period. If a planned dose of belantamab mafodotin 
was held/missed for any reason, the next dose can be administered at Day 1 of the next 
planned 28-day cycle, as long as the interval between 2 consecutive doses is at least 56 
(3) days.  
• 1.9 mg/kg STRETCH will administer a 1.9 mg/kg dose administered on Day 1 of 
every alternate 28-day cycles (C1, C3, C5, C7 and so on.)  
Lenalidomide will be administered as 25 mg PO daily on Days 1-21 of each 28-day cycle 
in participants with estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2. The 
dose of lenalidomide will be reduced to 10 mg daily on Days 1 to 21 of each 28-day cycle 
in participants with eGFR 40-60 mL/min/1.73 m2.  


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Dexamethasone will be given 40 mg weekly PO or IV on Day 1, 8, 15 and 22 of each 
cycle. For participants >75 years of age, with body mass index (BMI) <18.5 kg/m2, the 
dose of dexamethasone can be reduced to 20 mg at the discretion of the investigator. 
On days when only lenalidomide and dexamethasone are taken at home, they should be 
taken in the morning approximately at the same time each day. On lenalidomide and 
belantamab mafodotin co-administration days, lenalidomide should be administered after 
administration of belantamab mafodotin. On days when lenalidomide pharmacokinetic 
(PK) samples will be collected, participants will be required to take their morning dose in 
the clinic. For Cycle 1, the 24 h post-dose lenalidomide PK sample must be collected 
before lenalidomide dosing on Cycle 1 Day 2. 
Participants who are assigned to Arm A may continue combination treatment until the 
occurrence of progressive disease (PD), intolerable AEs, consent withdrawal, death, or 
end of study. In case of intolerable AEs related to Len/Dex in combination, the 
participant may be allowed to continue on belantamab mafodotin monotherapy.   
Arm B – Belantamab mafodotin in combination with Bor/Dex 
In Arm B, belantamab mafodotin is given up to 3 dose levels and up to 4 dosing 
schedules in combination with Bor/Dex on a 21-day cycle (Table 2).  
Table 2 
Arm B Dosing Regimens 
Arm B 
Part Dose 
Level 
Cohort 
Dose of 
Belantamab 
Mafodotin 
Schedule of 
Belantamab 
Mafodotin 
SoA  
Bor/Dex 
treatment 
(Cycle 1-8) 
21-day 
Cycle 
1 and 
2 
1 
2.5 mg/kg 
SINGLE 
2.5 mg/kg IV  
Day 1 
Table 7 
Bortezomib 
1.3mg/m2 SC or IV 
on D1, D4, D8, 
D11;  
Dexamethasone 
20mg PO or IV on 
D1, D2, D4, D5, 
D8, D9, D11, D12)  
2 
 
2.5 mg/kg 
SPLIT 
1.25 mg/kg IV  
Day 1, Day 8 
Table 8 
1 and 
2 
2 
3.4 mg/kg 
SINGLE 
 3.4 mg/kg IV  
Day 1 
Table 7 
2 
 
3.4 mg/kg 
SPLIT 
 1.7 mg/kg IV  
Day 1, Day 8 
Table 8 
2 
 
2.5 mg/kg 
STRETCH 
 2.5 mg/kg IV  
Day 1 in every 
alternate cycle 
(i.e. C1, C3, C5, 
C7 and so on) 
Table 9 
2 
 
S/D 
STRETCH 
Cycle 1:  2.5 
mg/kg IV  
Cycle 3+:  1.9 
mg/kg IV  
Day 1 in every 
alternate cycle 
Table 9 
2 
 
1.9 mg/kg 
SINGLE 
1.9 mg/kg IV 
Day 1 
Table 7 
2 
 
1.9 mg/kg 
STRETCH 
1.9 mg/kg IV 
Day 1 in every 
alternate cycle 
Table 9 
 
For SINGLE dosing schedule, belantamab mafodotin will be administered FIRST (prior 
to Bor/Dex) as a single full dose on Day 1 (D1) of every 21-day cycle as a 30-60 min 
infusion, followed by 1 to 2 h rest period.  


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• 3.4 mg/kg SINGLE dosing schedule will administer a 3.4 mg/kg dose on Day 1 of 
each 21-day cycle 
• 2.5 mg/kg SINGLE dosing schedule will administer a 2.5 mg/kg dose on Day 1 of 
each 21-day cycle 
• 1.9 mg/kg SINGLE dosing schedule will administer a 1.9 mg/kg dose on Day 1 of 
each 21-day cycle  
For SPLIT dosing schedule, belantamab mafodotin will be administered FIRST (prior 
to Bor/Dex) in the clinic in two equal divided doses - one on Day 1 and the other on Day 
8 of each 21-day cycle as a 30-60 min infusion, followed by a 1 to 2 h rest period.  
• 3.4 mg/kg SPLIT dosing schedule will administer a 1.7 mg/kg dose on Day 1 and 
a 1.7 mg/kg dose on Day 8 of each 21-day cycle 
• 2.5 mg/kg SPLIT dosing schedule will administer a 1.25 mg/kg dose on Day 1 
and a 1.25 mg/kg dose on Day 8 of each 21-day cycle 
For STRETCH dosing schedule, belantamab mafodotin will be administered FIRST 
(prior to Bor/Dex) as a single dose on Day 1 of every alternate 21-day cycle as a 30-60 
min infusion, followed by 1 to 2 h rest period. If a planned dose of belantamab mafodotin 
was held/missed for any reason, the next dose can be administered at Day 1 of the next 
planned 21-day cycle, as long as the interval between 2 consecutive doses is at least 42 
(3) days. 
• 2.5 mg/kg STRETCH will administer a 2.5 mg/kg dose on Day 1 of every 
alternate 21-day cycles (C1, C3, C5, C7 and so on)  
• 1.9 mg/kg STRETCH will administer a 1.9 mg/kg dose administered on Day 1 of 
every alternate 21-day cycles (C1, C3, C5, C7 and so on)  
For Step-Down (S/D) STRETCH dosing schedule, belantamab mafodotin will be 
administered FIRST (prior to Bor/Dex) as a 2.5 mg/kg dose on Day 1 of Cycle 1 
followed by subsequent planned doses of 1.9 mg/kg starting on Day 1 of alternate 21-day 
cycles (C3, C5, C7, and so on), as a 30-60 min infusion, followed by 1 to 2 h rest period. 
Bortezomib will be administered at 1.3 mg/m2 SC or IV (depending on participants’ and 
institutional preference) on Days 1, 4, 8, and 11 of every 21-day cycle for a total of up to 
8 cycles. The administration of bortezomib will be after belantamab mafodotin 
administration, approximately after 1 h and after assuring that participant is clinically 
stable. 
Dexamethasone will be administered at 20 mg PO or IV on Days 1, 2, 4, 5, 8, 9, 11, and 
12 of every 21-day cycle. Dexamethasone dose may be reduced at the investigator’s 
discretion for participants >75 years of age with BMI <18.5 kg/m2. Dexamethasone will 
be given for a total of up to 8 cycles.   
Participants completing 8 cycles of combination therapy will continue treatment with 
belantamab mafodotin as monotherapy until PD, intolerable AEs, consent withdrawal, 
death, or end of study. In case of intolerable AEs related to Bor/Dex in combination, the 
participant may be allowed to continue on belantamab mafodotin monotherapy. 


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Study Population 
The study will enroll adult participants with RRMM, who have undergone stem cell 
transplant (SCT), or are considered transplant ineligible, and who have been previously 
treated with at least 1 prior line of therapy, and who have documented evidence of 
disease progression during or after their most recent therapy.  
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
1. Capable of giving signed informed consent which includes compliance with the 
requirements and restrictions listed in the informed consent form (ICF) and in this 
protocol. 
2. Male or female, 18 years or older (at the time consent is obtained). 
3. Have confirmed diagnosis of Multiple Myeloma as defined by the International 
Myeloma Working Group (IMWG) criteria [Rajkumar, 2016]. 
4. Eastern Cooperative Oncology Group (ECOG) performance status:  
• For Arm A only: 0 to 1  
• For Arm B only: 0 to 2  
5. Have undergone autologous SCT, or are considered transplant ineligible 
6. Have been previously treated with at least 1 prior line of MM therapy and must have 
documented disease progression during or after their most recent therapy. 
7. Must have at least ONE aspect of measurable disease, defined as one of the 
following:  
a. Urine M-protein excretion ≥200 mg/24 h, or 
b. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or 
c. Serum free light chain (FLC) assay:  involved FLC level ≥10 mg/dL (≥100 mg/L) 
and an abnormal serum free light chain ratio (<0.26 or >1.65). 
8. Participants with a history of autologous SCT are eligible for study participation 
provided the following eligibility criteria are met: 
a. 
Autologous SCT was >100 days prior to study enrollment 
b. No active bacterial, viral, or fungal infection(s) present 
c. 
Participant meets the remainder of the eligibility criteria outlined in this protocol 
9. All prior treatment-related toxicities (defined by National Cancer Institute Common 
Toxicity Criteria for Adverse Events (NCI-CTCAE, Version 4.03, 2010) must be 
Grade 1 at the time of enrollment, except for alopecia. Patients with Grade 2 
neuropathy can be enrolled into Len/Dex treatment arm, but not into Bor/Dex 
treatment arm. 


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10. Adequate organ system functions as defined by the laboratory assessments listed in 
the table below (Adequate Organ System Function based on Safety Assessments). 
Adequate Organ System Function based on Safety Assessments 
Organ System and Laboratory 
Tests 
Laboratory Values 
Hematologic 
Absolute neutrophil count (ANC)a 
1.5 × 109/L 
Hemoglobin 
8.0 g/dL 
Platelets 
75 × 109/L 
Hepatic 
Total bilirubin 
≤1.5 × ULN; (Isolated bilirubin >1.5 × ULN is acceptable if bilirubin 
is fractionated and direct bilirubin is <35%) 
Alanine aminotransferase (ALT) 
2.5 × ULN 
Renal 
eGFRb 
40 mL/min/1.73 m2 
Spot urine (albumin/creatinine ratio 
from spot urine) 
500 mg/g (56 mg/mmol) 
Cardiac 
Left Ventricular Ejection Fraction 
(LVEF) by ECHO 
40%  
Note: Laboratory results obtained during Screening should be used to determine eligibility criteria.  In situations 
where laboratory results are outside the permitted range, the investigator may re-test the participant and the 
subsequent within range screening result may be used to confirm eligibility. 
a. 
Without growth factor support for the past 14 days, excluding erythropoietin 
b. 
As calculated by Modified Diet in Renal Disease (MDRD) formula 
 
11. Female Participants: 
Contraceptive use by women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies. 
A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least 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 belantamab 
mafodotin and agrees not to donate eggs (ova, oocytes) for the purpose of 
reproduction during this period.  
The investigator should evaluate the effectiveness of the contraceptive method in 
relationship to the first dose of study intervention. 


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The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
Additional Inclusion Criteria for WOCBP Participants Assigned to Arm A 
Due to lenalidomide being a thalidomide analogue with risk for embryo-fetal toxicity and 
prescribed under a pregnancy prevention/controlled distribution program, WOCBP 
participants will be eligible if they commit either to abstain continuously from 
heterosexual sexual intercourse or to use two methods of reliable birth control (one 
method that is highly effective), beginning 4 weeks prior to initiating treatment with 
lenalidomide, during therapy, during dose interruptions and continuing for 4 weeks 
following discontinuation of lenalidomide treatment. Thereafter, WOCBP participants 
must use a contraceptive method that is highly effective (with a failure rate of <1% per 
year) for a further 3 months, and agree not to donate eggs (ova, oocytes) for the purpose 
of reproduction during this period. 
Two negative pregnancy tests must be obtained prior to initiating lenalidomide therapy. 
The first test should be performed within 10-14 days and the second test within 24 hours 
prior to prescribing lenalidomide therapy. 
Additional Inclusion Criteria for WOCBP Participants Assigned to Arm B 
WOCBP assigned to Arm B 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 belantamab mafodotin or 7 months from the 
last dose of bortezomib, whichever is longer. 
12. Male Participants: 
Contraceptive use by men should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies.  
Male participants are eligible to participate if they agree to the following: 
• Arm A: from the time of first dose of study until 6 months after the last dose 
of belantamab mafodotin or 4 weeks from last dose of lenalidomide, 
whichever is longer, to allow for clearance of any altered sperm. 
• Arm B: from the time of first dose of study until 6 months after the last dose 
of belantamab mafodotin or 4 months from the last dose of bortezomib, 
whichever is the longer, to allow for clearance of any altered sperm. 
Refrain from donating sperm and 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: 


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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. Male participants should 
also use a condom with pregnant females. 
If the female partner of the male participant is pregnant at the time of enrollment, or 
becomes pregnant during the trial, the male participant must agree to remain abstinent 
(if it is consistent with their preferred and usual lifestyle) or use a male condom. 
Exclusion Criteria 
A participant will not be eligible for inclusion in this study if any of the following criteria 
apply: 
1. Systemic anti-myeloma therapy (including systemic steroids) within 14 days, or 
plasmapheresis within 7 days prior to the first dose of study drug. 
2. Use of an investigational drug within 14 days or five half-lives (whichever is longer) 
preceding the first dose of study drug.  
3. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose 
of study drugs. 
4. Prior allogenic stem cell transplant.  
Note: Participants who have undergone syngeneic transplant will be allowed only if 
they have no history and no currently active, graft versus host disease (GvHD) 
5. Evidence of active mucosal or internal bleeding. 
6. Any major surgery within the last four weeks. 
7. 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 fulfill criteria given in table of 
Adequate Organ System Function based on Safety Assessments. 
8. 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.  
9. Current active liver or biliary disease (with the exception of Gilbert's syndrome or 
asymptomatic gallstones, or otherwise stable chronic liver disease per investigator's 
assessment). 
10. Participants with invasive malignancies other than multiple myeloma are excluded, 
unless the second malignancy has been considered medically stable for at least 2 
years. The participant must not be receiving active therapy, other than hormonal 
therapy for this disease. 
Note: Participants with curatively treated non-melanoma skin cancer are allowed 
without a 2-year restriction  
11. Evidence of cardiovascular risk including any of the following: 


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a. Evidence of current clinically significant untreated arrhythmias, including 
clinically significant ECG abnormalities including 2nd degree (Mobitz Type II) or 
3rd degree atrioventricular (AV) block. 
b. History of myocardial infarction, acute coronary syndromes (including unstable 
angina), coronary angioplasty, or stenting or bypass grafting within 3 months of 
Screening. 
c. Class III or IV heart failure as defined by the New York Heart Association 
functional classification system. 
d. Uncontrolled hypertension. 
12. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to 
drugs chemically related to belantamab mafodotin, or any of the components of the 
study treatment. 
13. Pregnant or lactating female. 
14. Active infection requiring treatment. 
15. Known HIV infection. 
16. 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) 
17. 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. 
Hepatitis RNA testing is optional and participants with negative Hepatitis C 
antibody test are not required to also undergo Hepatitis C RNA testing  
18. Current corneal disease except for mild punctate keratopathy. 
Note: Participants with mild punctate keratopathy are allowed.   
Additional Exclusion Criteria for Participants Assigned to Arm A (belantamab 
mafodotin plus Len/Dex) 
19. Participants unable to tolerate antithrombotic prophylaxis must be excluded.  
20. Discontinuation of prior treatment with lenalidomide due to intolerable adverse 
events.  
Additional Exclusion Criteria for Participants Assigned to Arm B (belantamab 
mafodotin plus Bor/Dex) 
21. Unacceptable adverse effects from previous bortezomib treatment. 
22. Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain from previous 
bortezomib treatment. 
23. Intolerance or contraindications to anti-viral prophylaxis. 
Lifestyle Restrictions 
The following lifestyle restrictions apply while the participants are in the study:  


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• Contact lenses are prohibited while on the study treatment (from first dosing to 
the end of study treatment). Contact lens use may be restarted after the end of 
study treatment and a consultation with a qualified eye care specialist confirms 
there are no other contraindications. 
Use of bandage contact lenses is permitted during study treatment as directed by a 
qualified eye care specialist. 
• Participants must not donate blood while receiving study treatment; participants in 
Arm A must not donate blood for 28 days following discontinuation of 
lenalidomide. 
• Intraocular pressure may become elevated with dexamethasone treatment in some 
individuals. Intraocular pressure should be monitored. 
Final Analysis and End of Study Definitions:  
Participants in all arms will be treated until confirmed PD, death, start of a new 
anticancer treatment, withdrawal of consent, or end of the study, whichever occurs first. 
Following 12 months post last subject first dose, the final analysis will occur and the 
study will move into the post analysis continued treatment (PACT) phase. At that time, 
the collection of new data for all recruited participants who no longer receive study 
treatment will stop entirely and the clinical trial database will be closed. Those 
participants still benefiting from study drug in the opinion of their treating physician may 
continue to receive study drug (s).  In case the participant meets stopping criteria for 
belantamab mafodotin, the participant will discontinue all treatment and will continue to 
be monitored as per standard of care at the participant’s particular study site. SAEs, AEs 
leading to treatment discontinuation, overdose, pregnancy cases, and pre-specified ocular 
data will be reported directly to GSK. The end of study is defined when the last patient 
had their last visit (last subject last dose plus 70 days SAE reporting period). 
 
 


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2. 
STUDY SCHEMA 
Figure 1 
Schematic of Study Structure for Arm A (Belantamab Mafodotin with 
Len/Dex) 
 
a. 
Belantamab mafodotin (GSK2857916) SINGLE = full assigned dose of belantamab mafodotin administered on 
Day 1 of any 28-day cycle. 
b. 
Lenalidomide (25 mg on Days 1-21) + Dexamethasone (40 mg on Days 1, 8, 15, and 22) of any 28-day cycle. 
c. 
Belantamab mafodotin 2.5 mg/kg SPLIT= 1.25 mg/kg on Day 1 and 1.25 mg/kg on Day 8 of any 28-day cycle. 
d. *Belantamab mafodotin 1.9 mg/kg STRETCH = belantamab mafodotin 1.9 mg/kg dose administered on Day 1 of 
alternate 28-day cycles i.e. Q8W (C1, C3, C5, C7 and so on)- this cohort may be evaluated if emerging data 
suggests that this schedule may further optimize the tolerability or offers an improved benefit/risk profile. 
All participants will be operated under Amendment 03. 
Note: Combination therapy continued until PD, death, intolerable toxicity, consent withdrawn. Cohorts followed up for 
 and 
 
DE=Dose Escalation decision 
 
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Figure 2 
Schematic of Study Structure for Arm B (Belantamab Mafodotin with 
Bor/Dex) 
 
 
a. 
Belantamab mafodotin (GSK2857916) SINGLE = full assigned dose of belantamab mafodotin (1.9 mg/kg, 2.5 
mg/kg or 3.4 mg/kg) administered on Day 1 of any 21-day cycle. 
b. 
Bortezomib (1.3 mg/m2 on Days 1, 4, 8, and 11) + Dexamethasone (20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12) of 
any 21-day cycle. 
c. 
Belantamab mafodotin 2.5 mg/kg SPLIT= 1.25 mg/kg on Day 1 and 1.25 mg/kg on Day 8 of any 21-day cycle. 
d. 
Belantamab mafodotin 3.4 mg/kg SPLIT= 1.7 mg/kg on Day 1 and 1.7 mg/kg on Day 8 of any 21-day cycle. 
e. 
Belantamab mafodotin STRETCH= belantamab mafodotin 1.9 mg/kg or 2.5 mg/kg dose administered on Day 1 of 
alternate 21-day cycles i.e. Q6W (C1, C3, C5, C7 and so on). 
f. 
Belantamab mafodotin Step-Down (S/D) STRETCH = belantamab mafodotin 2.5 mg/kg dose at C1D1 followed 
by 1.9 mg/kg step-down dose on Day 1 of alternate 21-day cycles C3 onwards (C3, C5, C7, and so on). 
All participants will be operated under Amendment 03.  
#New cohorts in Amendment 3. 
Note: Combination therapy continued for up to 8 combination cycles; belantamab mafodotin further continued until PD, 
death, intolerable toxicity, consent withdrawn. Cohorts followed up for 
 and
 
DE=Dose Escalation decision; 
; PD=Progressive Disease; 
; 
S/D=Step-down. 
 
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3. 
SCHEDULE OF ACTIVITIES 
The two treatment arms use different cycle lengths to accommodate the approved 
standard of care (SoC) regimens for lenalidomide plus dexamethasone (Len/Dex; Arm A, 
28-day cycle) and bortezomib plus dexamethasone (Bor/Dex; Arm B, 21-day cycle) in 
combination with belantamab mafodotin. 
The different schedule of activities (SoA) tables are identified (Table 3): 


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Table 3 
List of Schedule of Activities Tables 
Study Phase 
Arm 
Dosing schedule 
Table 
Screening 
All 
All 
Table 4 
 
On-Treatment 
Arm A 
SINGLEa and STRETCHb  
Table 5 
SPLITc 
Table 6 
 
On-Treatment 
Arm B 
SINGLEa 
Table 7 
SPLITc 
Table 8 
STRETCHb and S/D STRETCHd 
Table 9 
 
End of Treatment 
All 
All 
Table 10 
a. 
SINGLE Dosing Schedule: belantamab mafodotin will be administered as a SINGLE full dose on Day 1 of 
each 28-day (Arm A) or 21-day (Arm B) cycle. 
b. 
STRETCH Dosing Schedule: belantamab mafodotin will be administered as a SINGLE full dose on Day 1 of 
every alternate 28-day (Arm A) or 21-day (Arm B) cycle. In Arm A, Len/Dex will continue to be administered 
every 28-day cycle as per SoC. In Arm B, Bor/Dex will continue to be administered every cycle for the first 8 
cycles (21-day cycles) as. per SoC. 
c. 
SPLIT Dosing Schedule: belantamab mafodotin will be split into two equal halves and each half dose will be 
administered on Day 1 and Day 8 of each 28-day (Arm A) or 21-day (Arm B) cycle.  
d. 
Step-Down (S/D) STRETCH Dosing Schedule: belantamab mafodotin will be administered as a SINGLE full 
dose on Day 1 of every alternate 28-day (Arm A) or 21-day (Arm B) cycle. The dose of belantamab 
mafodotin will be 2.5 mg/kg in C1 followed by a step-down dose of 1.9 mg/kg on Day 1 of every alternate 
cycle from C3 onwards (C3, C5, C7 and so on). In Arm A, Len/Dex will continue to be administered every 
28-day cycle as per SoC. In Arm B, Bor/Dex will continue to be administered every cycle for the first 8 cycles 
(21-day cycles) as per SoC. 
 
PACT Phase: All participants who continue to receive study treatment during the PACT 
phase will be monitored and receive follow-up care in accordance with standard local 
clinical practice. Assessments will revert to the standard of care at the participant’s 
particular study site and only SAEs, AEs leading to discontinuation of study treatment, 
overdoses, prespecified ocular data, and pregnancies will be reported directly to the 
Sponsor via paper forms (see Section 9 and Section 10.2). For participant discontinuing 
treatment in the PACT phase, no end of treatment visit is required.


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Table 4 
Schedule of Activities – SCREENING Assessments for Arm A (belantamab mafodotin in combination with 
lenalidomide plus dexamethasone) and Arm B (belantamab mafodotin in combination with bortezomib plus 
dexamethasone) 
Study Assessments1 
Screen 
Notes (Screening Arm A and Arm B) 
Informed Consent 
X 
1. 
All assessments apply to Part 1 and 2 unless stated otherwise. All screening assessments must be performed 
within 21 days prior to first dose unless otherwise specified. Informed consent form must be signed before any 
study-specific assessments are performed. Screening Assessments do not need to be repeated on Cycle 1 Day 
1 (C1D1), unless otherwise specified. 
2. 
Any SAEs assessed as related to study participation (e.g., protocol-mandated procedures or invasive tests) will 
be recorded from the time a participant consents to participate in the study through 
follow-up. See Section 
10.2.1 for details. 
3. 
Screening ocular examinations to be performed by a qualified eye care specialist within 21 days prior to first 
dosing. See Section 10.6.7.1 for list of ophthalmic exam procedures and Appendix 12 for qualifications and 
requirements of the eye care specialist. 
4. 
Refer to Section 10.6.10 for a comprehensive list of lab tests that must be collected for all participants. If labs 
are completed within 72 h prior to the first dose, this assessment need not be repeated on C1D1. 
5. 
Albumin/creatinine ratio (Spot urine from first void) will be performed at local lab, if local testing is not available 
then by central laboratory. 
6. 
Hep C RNA testing is optional but may be done to determine participant eligibility, if Hep C antibody is positive. 
If Hep C RNA is positive, participant is ineligible. See Section 7 Study Population for details. 
7. 
Perform only in women of child-bearing potential (WOCBP). WOCBP in Arm A: Two negative serum pregnancy 
tests must be obtained prior to initiating treatment; one may be performed within 14 days of C1D1, but the 
second must be performed within 24 h of C1D1. WOCBP in Arm B: A serum pregnancy test must be performed 
at screening; if the test is completed within 72 hours prior to the first dose of belantamab mafodotin, this 
assessment does not have to be repeated on C1D1. For questionable cases, follicle stimulating hormone (FSH) 
and estradiol (as needed in WOCBP only) should be performed at local lab. 
8. 
Single ECG on Screening.  All ECGs will be collected centrally (refer to SRM for details). 
9. 
ECHO to be performed locally. Screening ECHO may be performed up to 30 days prior to C1D1.  
10. Only in participants with IgD/IgE myeloma. 
11. Imaging is only required for participants with extramedullary disease by either CT, MRI, or PET/CT per local 
guidance. Screening assessment may be performed up to 30 days prior to C1D1. Needs to be performed by the 
same method throughout the study as was done at baseline (i.e. if CT/PET scan was used as baseline, 
participant needs to be followed by CT/PET scans). Selected target lesion needs to be measured and followed 
over time. Plasmacytoma measurements should be taken from the CT portion of the PET/CT, or MRI scans, or 
dedicated CT scans where applicable. For participants with only skin involvement, skin lesions should be 
Baseline Demographics 
X 
Medical History, disease history and 
characteristics  
X 
ECOG Performance Status 
X 
Adverse Events/SAEs2 
X 
Concomitant Medications 
X 
 
Safety 
Physical Exam 
X 
Ocular Exam3 
X 
Vital Signs (BP, Heart rate, Body 
Temperature) 
X 
Body Weight (BW) and Height 
X 
Hematology4 
X 
Clinical chemistry4 
X 
HbA1c 
X 
C-reactive protein (CRP)4 
X 
Urinalysis (dipstick)4  
X 
Estimated Glomerular Filtration Rate 
(eGFR) by MDRD formula 
X 
Spot urine for albumin/creatinine ratio5 
X 
HbsAg, HbcAb, and Hepatitis C 
antibody. Hepatitis C RNA optional6 
X 
Pregnancy Test for WOCBP7 
X 
12-lead ECG8 
X 
ECHO – LVEF9 
X 
Disease Evaluation 
β2 microglobulin 
X 
SPEP (Serum Protein Electrophoresis) 
X 
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Study Assessments1 
Screen 
Notes (Screening Arm A and Arm B) 
Serum Kappa, lambda free LC, FLC 
ratio 
X 
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). 
12. Imaging of bones for lytic lesions by method aligned with institutional guidance (X-ray, CT or MRI). Survey 
results within 30 days prior to C1D1 date are acceptable. 
13. BM aspirate/biopsy within 28 days prior to first dose is acceptable. 
14. Fluorescence-in-situ hybridization (FISH) testing to be performed locally at least for: t(4;14), t(14;16), amp(1q), 
del(1p) and del(17p13). If participant is known to have tested positive for t(4;14) or  t(14;16) on previous tests 
regardless of timeframe, FISH for these translocations does not need to be repeated. FISH results for amp(1q), 
del(1p) and del(17p13) from samples taken within 60 days prior to first dose are acceptable. If testing cannot be 
performed at a local lab the samples can be sent to the central lab. 
15. 
 to be performed by the central lab at the time of first achieving VGPR or better. 
Thereafter, 
testing should be repeated every 6 months until PD or CR. In case of deepening of response 
from VGPR to CR, or achieving CR without prior VGPR, 
 testing should be performed at the time of 
achieving suspected CR and repeated every 6 months until PD. Whenever possible, a further BM aspirate 
sample may be taken at the same time for biomarker analysis. 
16. Samples will be submitted to central lab for BCMA analysis, any remaining bone marrow aspirate sample will be 
used for biomarker research.  
 
Serum Immunofixation 
X 
UPEP (Urine Protein Electrophoresis) 
(on 24 h collected urine) 
X 
Urine Immunofixation 
X 
Ca corrected for Albumin (Serum) 
X 
IgG, IgM, IgA 
X 
IgD/IgE10 
X 
Imaging for extramedullary disease11 
X 
Skeletal Survey12 
X 
 
Bone Marrow Tests 
BM aspirate/biopsy for Disease 
Assessment13 
X 
BM for FISH testing14 
X 
BM for 
 
testing15 
X 
BM aspirate for BCMA expression and 
biomarker research15,16 
X 
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Table 5 
Schedule of Activities – On-Study Assessments for Arm A (belantamab mafodotin in combination with 
lenalidomide plus dexamethasone) [28-Day Cycle] - belantamab mafodotin SINGLE and STRETCH Dosing 
Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
ECOG Performance Status 
 
 
X 
 
1. 
All assessments apply to Part 1 and 2 of the study, unless 
stated otherwise. 
2. 
Screening assessments do not need to be repeated on Cycle 
1 Day 1 (C1D1), unless otherwise specified. 
3. 
All assessments starting at week 5 can be performed within 3 
days prior to the scheduled date, unless otherwise specified. 
4. 
Assessments scheduled on days of dosing should be done 
prior to drug administration, unless otherwise specified. 
Physical Exam must be conducted within 72 h prior to 1st 
dose of study drugs administrated in that cycle. Body weight 
at C1D1 (prior to dosing) will be used for dose calculation of 
belantamab mafodotin.  Body weight to be measured prior to 
each dose. If the change of body weight is greater than 10%, 
Adverse Events / SAEs5 
X 
X 
Ongoing 
Ongoing 
Concomitant Medications 
X 
X 
Ongoing 
Ongoing 
Safety 
Physical Exam 
X 
X 
X 
X4 
Ocular Exam6 
 
X 
X 
X 
Vital Signs (BP, Heart rate, 
Body Temperature)7 
X 
X 
 
X 
Body Weight (BW) and Height 
BW only 
BW only 
 
BW only 
Hematology8,9 
X 
X 
X 
X 
Clinical chemistry8 
X 
X 
X 
X 
HbA1c 
As clinically indicated 
C-reactive protein (CRP)8 
 
X 
X 
 
Urinalysis (dipstick)8 
X 
X 
X 
 


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Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
Estimated Glomerular 
Filtration Rate (eGFR) by 
MDRD formula 
X 
X 
X 
 
the dose should be re-calculated based on the actual body 
weight at the time of dosing.  
5. 
All AEs will be assessed for at least 70 days after the last 
dose regardless of initiation of new anticancer therapy. All 
related SAEs are to be collected from consent through 
 
follow-up. For reporting of ocular events see the guidance 
provided in Appendix 8. 
6. 
Participants will be assessed by a qualified eye care specialist 
(Appendix 12) on Day 1 of every cycle prior to dosing up to 
Dose 6 of belantamab mafodotin (assessment window of up 
to 5 days prior to dosing, but all effort should be made to 
schedule as close to belantamab mafodotin dosing as 
possible). If there are no significant ocular examinations 
findings, patient’s symptoms or vision changes at the time of 
Dose 6 exam, participants may have their ophthalmologic 
exams decreased to once every 3 months. If a participant 
subsequently develops vision changes or other ocular 
symptoms, the participant should be promptly evaluated by a 
qualified eye care specialist. In case of persistent ophthalmic 
Spot urine for 
albumin/creatinine ratio10 
 
X 
X 
 
Pregnancy Test for WOCBP11 
X 
X 
X 
X 
12-lead ECG12 
X 
X 
 
X 
ECHO – LVEF13 
 
 
Every 12 
weeks  
(At weeks 13, 
25, 37, 49 etc) 
 
 
Disease Evaluation [every 4 weeks (3 days) even if the cycle is delayed]14 
SPEP (Serum Protein 
Electrophoresis) 
 
X 
X 
 
Serum Kappa, lambda free 
LC, FLC ratio 
 
X 
X 
 
Serum Immunofixation15 
 
 
At time of 
suspected CR 
 
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Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
then until 
suspected PD 
exam findings, newly developed ocular symptoms or vision 
changes at Dose 6 exam, the participants will have further 
ophthalmologic exams, at least every cycle until resolution (to 
Grade 1 or baseline) or more frequently as clinically indicated 
by the qualified eye care specialist. See Section 10.6.7.1 for 
full details of ocular exam procedures. 
7. 
On each belantamab mafodotin dosing day, vital signs must 
be assessed within 30 min prior to Start of Infusion (SOI), 
within 15 min after End of Infusion (EOI), and at 1 h (15 min) 
after EOI. On days where vital sign assessments align with 
PK sampling time points, vital signs should be assessed prior 
to belantamab mafodotin PK samples being drawn. 
8. 
Hematology and clinical chemistry must be repeated if not 
done within 24 h prior to 1st dose of study drugs administered 
in that cycle. Refer to Table 27 for comprehensive list of lab 
tests. 
9. 
To be performed up to 24 h before D1, D8, D15, D22 in C1 
and C2; then up to 24 h before D1, D15 in C3 to C8 and then 
up to 24 h before D1 of each cycle from C9 onwards, or more 
UPEP (Urine Protein 
Electrophoresis) 
(on 24 h collected urine) 
 
X 
X 
 
Urine Immunofixation15 
 
 
At time of 
suspected CR 
then until 
suspected PD 
 
Ca corrected for Albumin 
(Serum) 
 
X 
X 
 
IgG, IgM, IgA 
 
X 
X 
 
IgD/IgE16 
 
X 
X 
 
Imaging for extramedullary 
disease17 
 
 
Week 13, 25, 
37, 49 and 
then if clinically 
indicated 
 
Skeletal Survey18 
 
As clinically 
indicated 
As clinically 
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Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
Whole body PET/CT 
 
 
Only once at 
time of 
achieving CR 
or sCR 
(whichever 
comes first) 
according to 
IMWG 2016 
 
frequently, if clinically indicated. On D1 of any planned cycle, 
Absolute Neutrophil Count (ANC) must be ≥1.0×109/L to 
administer treatment.  
10. Albumin/creatinine ratio (Spot urine from first void) every 4 
weeks 3 days (local lab, if not available then central 
laboratory testing). 
11. Perform only in women of childbearing potential. Two 
negative serum pregnancy tests must be obtained prior to 
initiating therapy with lenalidomide; one may be performed 
within 10-14 days of C1D1, but the second must be 
performed within 24 h of C1D1. After the first dose of 
belantamab mafodotin, pregnancy test will be done weekly 
during the first month, then monthly thereafter in females with 
regular menstrual cycles or every 2 weeks in females with 
irregular menstrual cycles. Subsequent pregnancy test on 
dosing days may be either serum or urine test. Each 
pregnancy test must be performed within 24 h prior to dosing. 
12. SINGLE ECG performed pre-infusion on belantamab 
mafodotin dosing days. On days when belantamab mafodotin 
Response assessment by 
IMWG19 
 
X 
X 
 
Bone Marrow Tests 
BM aspirate/biopsy for 
Disease Assessment20, 24 
 
 
 At time of 
suspected CR 
or at time of 
suspected PD 
(only if PD not 
evident 
otherwise) 
 


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Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
BM biopsy to confirm sCR by 
IHC 
 
 
 Upon 
achieving CR 
  
 
PK sampling is performed, PK samples should be drawn 
shortly after ECG. TRIPLICATE ECGs will be performed as 
described below with SINGLE ECG performed at all other 
times.  All ECGs will be collected centrally (refer to SRM for 
details). 
Belantamab mafodotin Dose 1 (Cycle 1) 
Day 1: TRIPLICATE ECGs Pre-infusion (within 30 min prior 
to SOI), EOI (up to 15 min after EOI), 2 h (±15 min) after SOI 
and 24 h (±2 h) after SOI.  
Day 4 (i.e. 72 h after SOI [±24 h]): TRIPLICATE ECG 
performed before PK sample. 
Belantamab mafodotin Dose 2  
Day 1: SINGLE ECG pre-infusion  
Belantamab mafodotin Dose 3  
Day 1:  TRIPLICATE ECGs pre-infusion (within 30 min prior 
to SOI), EOI (up to 15 min after EOI) 
13. ECHO will be performed every 12 weeks (7 days) and 
locally. 
BM aspirate for 
 
 testing21  
 
 
At time of 
achieving 
VGPR or 
better 
 
 
Biomarkers 
X 
 
 
X 
X 
 
At time of 
achieving 
VGPR or 
better21 
 
 
Optional 
Optional tissue sample at PD 
for BCMA expression and 
biomarker research24 
 
 
X 
 
Genetic sample25 
X 
 
 
 
CCI
CCI


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Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
 
 
 
14. Disease evaluation (except imaging and skeletal survey) will 
continue to be performed, every 4 weeks (3 days) even if 
the cycle is delayed. 
15. At time of first achieving SPEP or Urine M protein ~0 g/dl 
(suspected CR) and until suspected PD after CR or stringent 
Complete Response (sCR). 
16. Only in participants with IgD/IgE myeloma. 
17. Imaging is only required for participants with known 
extramedullary disease at week 13, 25, 37, 49 (7 days) and 
then if clinically indicated by either CT, MRI, or PET/CT per 
local guidance. Needs to be performed by the same method 
throughout the study as was done at baseline (i.e. if CT/PET 
scan was used as baseline, participant needs to be followed 
by CT/PET scans). Selected target lesion needs to be 
measured and followed over time. Plasmacytoma 
measurements should be taken from the CT portion of the 
PET/CT, or MRI scans, or dedicated CT scans where 
applicable.  
PK and ADA 
Pharmacokinetic blood 
sampling for belantamab 
mafodotin 22,26 
X26 
 
 
X (at selected 
cycles)26 
Pharmacokinetic blood 
sampling for lenalidomide27 
X27 
 
 
  
Anti-drug antibodies (ADA)28 
X28 
 
 
X (at selected 
cycles)28 
 
Treatment 
Premedication if needed29 
X 
 
 
X 
Administration of belantamab 
mafodotin30 
X 
 
 
SINGLE Dosing: 
Day 1 of each 28-
day cycle 


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Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
1.9 mg/ kg 
STRETCH: 1.9 
mg/kg on Day 1: 
at least 56 (3) 
days between 
consecutive doses 
of belantamab 
mafodotin. 
For participants with only skin 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). 
18. Imaging of bones for lytic lesions by method aligned with 
institutional guidance (X-ray, CT or MRI). Survey results 
within 30 days prior to C1D1 date are acceptable. At later 
cycles, repeat as clinically indicated, or if worsening clinical 
symptoms suggest PD, by the same method used as at 
screening.  
19. Response to treatment will be assessed every 4 weeks (3 
days), based on laboratory tests and imaging (if applicable), 
using IMWG criteria [Kumar, 2016]. 
20. Whenever CR is assessed, if possible, a further BM aspirate 
sample may be taken at the same time for biomarker 
research.  
21. 
) to be performed by the 
central lab at the time of first achieving VGPR or better. 
Thereafter, 
 should be repeated every 6 months 
until PD or CR. In case of deepening of response from VGPR 
Administration of 
lenalidomide31 
X 
X 
 
25 or 10 mg PO 
Days 1-21 of each 
28-day cycle 
Administration of 
dexamethasone32 
X 
X 
 
40 or 20 mg on 
Days 1, 8, 15, and 
22 of each 28-day 
cycle 
Preservative-free artificial 
tears33 
X 
Cooling eye masks33 
X 
 
 
X 
Venous Thrombo-Embolism 
(VTE) prophylaxis34 
X 
CCI
CCI


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Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
 
to CR, or achieving CR without prior VGPR, 
 
should be performed at the time of achieving suspected CR 
and repeated every 6 months until PD. Whenever possible, a 
further BM aspirate sample may be taken at the same time for 
biomarker research. Additionally, collect blood plasma for 
analysis. 
24. The optional PD tissue sample should contain tumor cells, 
either BM aspirate clot, or other tissue in case of 
extramedullary disease. Samples will be submitted to central 
lab for BCMA analysis, any remaining bone marrow and/or 
tissue sample will be used for biomarker research. 
25. Informed consent for optional sub-studies (e.g. genetic 
research) must be obtained before collecting a sample. The 
sample will be collected at the first opportunity after a 
participant has met all eligibility requirements, before/ on 
C1D1 prior to infusion. If insufficient DNA was extracted, or 
the sample was damaged or otherwise could not be 
Health Outcomes 
EORTC QLQ-C30 AND QLQ-
MY2035 
X 
 
Every 8 weeks 
starting W9 
 
PRO-CTCAE35 
X 
X 
X 
 
OSDI and NEI-VFQ-2535 
X 
X 
X 
 
 
CCI
CCI
CCI


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Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
processed, the site may be requested to recollect the genetic 
sample where applicable 
26. PK samples to be taken in all participants for belantamab 
mafodotin measurement on:  
Belantamab mafodotin Dose 1 (Cycle 1) 
Day 1: at pre-infusion (within 30 min prior to Start of 
Infusion), End of Infusion (0 to 15 min after EOI), at 2 h 
(± 15 min) after SOI and at 24 h (± 2 h) after SOI. 
Day 4 (i.e., 72 h after SOI [± 24h]), one PK sample to be 
taken after ECG performed. 
Day 8 through and including on Day 15:  One PK sample to 
be taken. 
Day 29 (STRETCH): One PK sample to be taken. 
Belantamab mafodotin Dose 2 
Day 1: at pre- infusion (within 30 min prior to SOI) and EOI 
(0 to 15 min after EOI). 
If Dose 2 is delayed, collect one PK sample on this day 
(Dose 1 Day 29 for SINGLE and Dose 1 Day 57 for 
STRETCH) regardless of dosing. 


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Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
Belantamab mafodotin Dose 3 
Day 1:  at pre- infusion (within 30 min prior to SOI) and EOI 
(0 to 15 min after EOI).  
Belantamab mafodotin Dose 6  
Day 1: at pre- infusion (within 30 min prior to SOI) and EOI 
(0 to 15 min after EOI). 
Belantamab mafodotin Dose 9: 
Day 1: at pre- infusion (within 30 min prior to SOI).  
Belantamab mafodotin Dose 12 
Day 1:  at pre-infusion (within 30 min prior to SOI). 
For treatment beyond belantamab mafodotin Dose 12, pre-
infusion samples will be collected every 6th Dose of 
belantamab mafodotin (Dose 18, Dose 24, Dose 30 and so 
on, until PD). 
 samples will be collected every time a 
belantamab mafodotin PK sample is collected. See footnote 
22. 
27. PK samples for lenalidomide: During C1D1, PK samples will 
be collected at pre-dose (within 30 min prior to taking drug), 
0.5 h (2 min), 1 h (5 min), 2 h (10 min), and 4 h (15 min) 
and 24 h (2 h) after the administration of lenalidomide. The 
CCI


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Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
24 h post-dose must be collected before lenalidomide 
dosing on C1D2. 
28. All ADA samples will be collected prior to each belantamab 
mafodotin infusion at Dose 1, 2, 3, 6, 9 and 12 (at the same 
time as the pre-infusion belantamab mafodotin PK samples 
are taken); for treatment beyond 12 cycles, collect samples 
for ADA analysis prior to each infusion every 6th Dose of 
belantamab mafodotin (Dose 18, Dose 24, Dose 30 and so on 
until PD). 
29. Premedication should be considered in any participant who 
experienced an IRR during the first or any subsequent 
infusions with belantamab mafodotin. 
30. Belantamab mafodotin will be administered first as a 30 min 
to 1 h infusion, followed by 1-2 h rest period. A window of 3 
days is acceptable for administration of study treatment after 
C1. Please refer to Section 8.2 for dose modification 
guidance. Note: “SINGLE” Dosing Schedule: belantamab 
mafodotin will be administered as a SINGLE full dose on Day 
1 of each cycle. For example: A “2.5 mg/kg SINGLE” dosing 
schedule of belantamab mafodotin will administer a 2.5 mg/kg 


TMF-14624358 
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207497 
 
Protocol Amd 04 
 
42 
 
Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
dose on D1 of each cycle. Note: STRETCH Dosing Schedule: 
belantamab mafodotin will be administered as a full dose on 
D1 of every alternate 28-day cycle. For example: A 1.9 mg/kg 
STRETCH will administer a 1.9 mg/kg dose on Day 1 of every 
alternate 28-day cycle i.e. STRETCH (C1, C3, C5, C7 and so 
on). 
31. Lenalidomide: 25 mg orally daily on Days 1 - 21 of each cycle 
in participants with >60 mL/min/1.73 m2, or reduced to 10 mg 
daily if the eGFR is 40-60 mL/min/1.73 m2. [Refer to 
lenalidomide PI]. Refer to Section 8.2 for dose modification 
guidance. 
32. Dexamethasone: 40 mg weekly, orally on Days 1, 8, 15, 22 of 
each cycle, Participants who are >75 y with BMI <18.5 kg/m2, 
the dose of dexamethasone can be reduced to 20 mg weekly. 
If intolerance to dexamethasone develops, dexamethasone 
may be reduced to 20 mg. If 20 mg is not tolerated, the 
dexamethasone dose can be further reduced or permanently 
discontinued. Refer to Section 8.2 for dose modification 
guidance. 


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Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
On days where only lenalidomide and dexamethasone are 
taken at home, they should be taken in the morning 
approximately at the same time each day. On C1D1, 
lenalidomide should be administered as close as possible to 
the end of the 1-2 h rest period after administration of 
belantamab mafodotin and no later than 6 h after the end of 
the rest period after administration of belantamab mafodotin. 
On subsequent lenalidomide and belantamab mafodotin co-
administration days such as C2D1, C3D1 and thereafter, 
lenalidomide should be administered after the end of the 1-2 h 
rest period after administration of belantamab mafodotin. 
Participant diary will be used to keep record of self-
administered oral study treatment(s) at home. 
33. Corneal Events Management:  
- Prophylactic preservative-free artificial tears must be 
administered in each eye at least 4-8 times daily beginning on 
C1D1 until end of treatment. 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.  


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Study Assessments1 
 
SINGLE 
and 
STRETCH 
Dosing 
 
STRETCH 
Dosing 
ONLY 
SINGLE and STRETCH Dosing 
Notes (Arm A belantamab mafodotin SINGLE and STRETCH 
dosing) 
Cycle 1 Day 
12 
Cycle 2 Day 
1 
Every 28 Days 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 - 
SINGLE dosing 
[or Starting at 
Cycle 3-
STRETCH 
dosing] 
 
(Prior to the first 
dose of any 
study drugs at 
the given cycle) 
- At the start of each infusion, participants may apply cooling 
eye masks for approximately 1 h or as long as tolerated. 
34. ASA or LMH or oral anticoagulants according to institutional 
guidance for the duration of treatment with lenalidomide. 
35. EORTC QLQ-C30 AND QLQ-MY20 will be collected every 8 
weeks, and PRO-CTCAE, OSDI and NEI-VFQ-25 will be 
collected every 4 weeks, even if cycle is delayed. Participants 
who cannot complete the self-administered version should 
use an Interviewer-Administered format. The interview may 
be administered over the telephone. If the Interviewer-
Administered format is used, it should be read to the 
participants verbatim, and participant responses should be 
recorded directly without any interpretation.  Refer to SRM for 
further details. 
 


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Table 6 
Schedule of Activities – On-Study Assessments for Arm A (belantamab mafodotin in combination with 
lenalidomide plus dexamethasone) [28-Day Cycle] – belantamab mafodotin SPLIT Dosing Only 
Study Assessments1 
Cycle 1  
Every 28 
Days 
 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm A belantamab mafodotin SPLIT dosing only) 
Day 12 
Day 8 
ECOG Performance Status 
 
 
X 
 
1. 
All assessments apply to Part 1 and 2 of the study unless stated otherwise. 
2. 
Screening assessments do not need to be repeated on Cycle 1 Day 1 (C1D1) 
unless otherwise specified. 
3. 
All assessments starting at week 5 can be performed within 3 days prior to the 
scheduled date unless otherwise specified. 
4. 
Assessments scheduled on days of dosing should be conducted prior to drug 
administration, unless otherwise specified. Physical Exam must be within 72 h 
prior to 1st dose of study drugs to be administrated in that cycle. Body weight at 
C1D1 (prior to dosing) will be used for dose calculation of belantamab 
mafodotin. Body weight to be measured prior to each dose. If the change of 
body weight is greater than 10%, the dose should be re-calculated based on the 
actual body weight at the time of dosing. 
5. 
Treatment-related toxicities will be assessed for at least 70 days after the last 
dose regardless of initiation of new anticancer therapy. All related SAEs are to 
be collected from consent through 
 follow-up. For reporting of ocular events 
see the guidance provided in Appendix 8. 
6. 
Participants will be assessed by a qualified eye care specialist (Appendix 12) on 
Day 1 of every cycle prior to dosing up to Dose 6 of belantamab mafodotin 
(assessment window of up to 5 days prior to dosing, but all effort should be 
made to schedule as close to belantamab mafodotin dosing as possible). If 
there are no significant ocular examinations findings, patient’s symptoms or 
vision changes at the time of Dose 6 exam, participants may have their 
ophthalmologic exams decreased to once every 3 months. If a participant 
subsequently develops vision changes or other ocular symptoms, the participant 
Adverse Events/ SAEs5 
X 
 
Ongoing 
Ongoing 
Concomitant Medications 
X 
 
Ongoing 
Ongoing 
 
Safety 
Physical Exam 
X 
X 
X 
X4 
Ocular Exam6 
 
 
 
X 
Vital Signs (BP, Heart rate, 
Body Temperature)7 
X 
X 
 
X 
Body Weight (BW) and 
Height 
BW only 
 
 
BW only 
Hematology8,9 
X 
X 
X 
X 
Clinical chemistry8 
X 
 
X 
X 
HbA1c 
As clinically indicated 
C-reactive protein (CRP)8 
 
 
X 
 
Urinalysis (dipstick)8 
X 
 
X 
 
Estimated Glomerular 
Filtration Rate (eGFR) by 
MDRD formula 
X 
 
X 
 
Spot urine for 
albumin/creatinine ratio10 
 
 
X 
 
Pregnancy Test for 
WOCBP11 
X 
 
X 
X 
12-lead ECG12 
X 
X 
 
X 
CC
I


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46 
 
Study Assessments1 
Cycle 1  
Every 28 
Days 
 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm A belantamab mafodotin SPLIT dosing only) 
Day 12 
Day 8 
ECHO – LVEF13 
 
 
Every 12 
weeks  
(At week 13, 
25, 37, 49 
and so on) 
 
should be promptly evaluated by a qualified eye care specialist. In case of 
persistent ophthalmic exam findings, newly developed ocular symptoms or 
vision changes at Dose 6 exam, the participants will have further 
ophthalmologic exams, at least every cycle until resolution (to Grade 1 or 
baseline) or more frequently as clinically indicated by the qualified eye care 
specialist. See Section 10.6.7.1 for full details of ocular exam procedures. 
7. On each belantamab mafodotin dosing day, vital signs must be assessed within 
30 min prior to Start of Infusion (SOI), within 15 min after End of Infusion (EOI), 
and at 1 h (15 min) after EOI. On days where vital sign assessments align with 
PK sampling time points, vital signs should be assessed prior to belantamab 
mafodotin PK samples being drawn. 
8. 
Hematology and clinical chemistry must be repeated, if not done within 24 h 
prior to 1st dose of study drugs to be administered in that cycle. Refer to Table 
27 for comprehensive list of lab tests. 
9. 
To be performed up to 24 h before D1, D8, D15, D22 in C1 and C2; then up to 
24 h before D1, D15 in C3 to C8 and then up to 24 h before Day 1 of each cycle 
from C9 onwards, or more frequently, if clinically indicated. On D1 of any 
planned cycle, Absolute Neutrophil Count (ANC) must be ≥1.0×109/L to 
administer treatment.  
10. Albumin/creatinine ratio (Spot urine from first void) every 4 weeks 3 days (local 
lab, if not available then central laboratory testing). 
11. Perform only in women of childbearing potential. Two negative serum 
pregnancy tests must be obtained prior to initiating therapy with lenalidomide; 
one may be performed within 10-14 days of C1D1, but the second must be 
performed within 24 h of C1D1. After the first dose of belantamab mafodotin, 
pregnancy test will be done weekly during the first month, then monthly 
thereafter in females with regular menstrual cycles or every 2 weeks in females 
 
Disease Evaluation [every 4 weeks (3 days) even if the cycle is delayed]14 
SPEP (Serum Protein 
Electrophoresis) 
 
 
X 
 
Serum Kappa, lambda free 
LC, FLC ratio 
 
 
X 
 
Serum Immunofixation15 
 
 
At time of 
suspected CR 
then until 
suspected PD 
 
UPEP (Urine Protein 
Electrophoresis) 
(on 24 h collected urine) 
 
 
X 
 
Urine Immunofixation15 
 
 
At time of 
suspected CR 
then until 
suspected PD 
 
Ca corrected for Albumin 
(Serum) 
 
 
X 
 
IgG, IgM, IgA  
 
 
X 
 
IgD/IgE16 
 
 
X 
 


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Study Assessments1 
Cycle 1  
Every 28 
Days 
 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm A belantamab mafodotin SPLIT dosing only) 
Day 12 
Day 8 
Imaging for extramedullary 
disease17 
 
 
Week 13, 25, 
37, 49 and 
then if 
clinically 
indicated 
 
with irregular menstrual cycles. Subsequent pregnancy test on dosing days may 
be either serum or urine test.  Each pregnancy test must be performed within 24 
h prior to dosing. 
12. SINGLE ECG performed pre-infusion on belantamab mafodotin dosing days. 
On days when belantamab mafodotin PK sampling is performed, PK samples 
should be drawn shortly after ECG. TRIPLICATE ECGs will be performed as 
described below, with SINGLE ECG performed at all other times.  All ECGs will 
be collected centrally (refer to SRM for details). 
Belantamab mafodotin Dose 1 (C1) 
Day 1: TRIPLICATE ECGs Pre-infusion (within 30 min prior to SOI), EOI (up to 
15 min after EOI), 2 h (±15 min) after SOI and 24 h (±2 h) after SOI.  
D4 (i.e. 72 h after D1 SOI [24 h]): TRIPLICATE ECG performed before PK 
sample. 
D8: TRIPLICATE ECGs Pre-infusion (within 30 min prior to SOI), EOI (up to 15 
min after EOI), 2 h (±15 min) after SOI and 24 h (±2 h) after SOI.  
D11 (i.e. 72 h after Day 8 SOI [24 h]): TRIPLICATE ECG performed before PK 
sample. 
Belantamab mafodotin Dose 2: 
D1: SINGLE ECG pre-infusion 
D8: SINGLE ECG pre-infusion 
Belantamab mafodotin Dose 3: 
D1: TRIPLICATE ECGs pre-infusion (within 30 min prior to SOI), EOI (up to 15 
min after EOI) 
D8: TRIPLICATE ECGs pre-infusion (within 30 min prior to SOI), EOI (up to 15 
min after EOI) 
13. ECHO will be performed every 12 weeks (7 days) and locally.  
14. Disease evaluation (except imaging and skeletal survey) will continue to be 
performed, every 4 weeks (3 days) even if the cycle is delayed. 
Skeletal Survey18 
 
 
As clinically 
indicated 
 
Whole body PET/CT 
 
 
Only once at 
time of 
achieving CR 
or sCR 
(whichever 
comes first) 
according to 
IMWG 2016 
 
Response assessment by 
IMWG19 
 
 
X 
 
 
Bone Marrow Tests 
BM aspirate/biopsy for 
Disease Assessment20,24 
 
 
 At time of 
suspected CR 
or at time of 
suspected PD 
(only if PD not 
evident 
otherwise) 
 
BM biopsy to confirm sCR 
by IHC 
 
 
 Upon 
achieving CR 
  
 


TMF-14624358 
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Protocol Amd 04 
 
48 
 
Study Assessments1 
Cycle 1  
Every 28 
Days 
 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm A belantamab mafodotin SPLIT dosing only) 
Day 12 
Day 8 
BM aspirate for 
 
 testing21 
 
 
At time of 
achieving 
VGPR or 
better 
 
15. At time of first achieving SPEP or Urine M protein ~0 g/dl (suspected CR) and 
until suspected PD after CR or stringent Complete Response (sCR). 
16. Only in participants with IgD/IgE myeloma. 
17. Imaging is only required for participants with known extramedullary disease at 
week 13, 25, 37, 49 (7 days) and then if clinically indicated by either CT, MRI, 
or PET/CT, per local guidance. Needs to be performed by the same method 
throughout the study as was done at baseline (i.e. if CT/PET scan was used as 
baseline, participant needs to be followed by CT/PET scans).  Selected target 
lesion needs to be measured and followed over time. Plasmacytoma 
measurements should be taken from the CT portion of the PET/CT, or MRI 
scans, or dedicated CT scans where applicable. 
For participants with only skin involvement, skin lesions should be measured 
with a ruler.  Measurement of tumor size will be determined by the Sum of the 
Products of the maximal perpendicular diameters of measured lesions (SPD). 
18. Imaging of bones for lytic lesions by method aligned with institutional guidance 
(X-ray, CT or MRI). Survey results within 30 days prior to C1D1 date are 
acceptable. At later cycles, repeat as clinically indicated, or if worsening clinical 
symptoms suggest PD, by the same method used as at screening. 
19. Response to treatment will be assessed every 4 weeks (3 days), based on 
laboratory tests and imaging (if applicable), using IMWG criteria [Kumar, 2016]. 
20. Whenever CR is assessed, if possible, a further BM aspirate sample may be 
taken at the same time for biomarker analysis. 
21. 
) to be performed by the central lab at the time of 
first achieving VGPR or better. Thereafter, 
 should be repeated 
every 6 months until PD or CR. In case of deepening of response from VGPR to 
CR, or achieving CR without prior VGPR, 
 should be performed at 
the time of achieving suspected CR and repeated every 6 months until PD. 
 
Biomarkers 
X 
 
 
X 
X 
 
At time of 
achieving 
VGPR or 
better21 
 
 
Optional 
Optional tissue sample at 
PD for BCMA expression 
and biomarker research24 
 
 
X 
 
Genetic sample25 
X 
 
 
 
 
PK and ADA 
Pharmacokinetic blood 
sampling for belantamab 
mafodotin22,26 
X26 
X26 
 
X (at selected 
cycles)26 
Anti-drug antibodies 
(ADA)27 
X27 
 
 
X (at selected 
cycles)27 
 
Treatment 
Premedication if needed28 
X 
 
 
X 
CCI
CCI
CCI
CCI
CCI


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49 
 
Study Assessments1 
Cycle 1  
Every 28 
Days 
 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm A belantamab mafodotin SPLIT dosing only) 
Day 12 
Day 8 
Administration of 
belantamab mafodotin29 
X 
X 
 
Day 1 and Day 
8 of each 28-
day cycle 
Whenever possible, a further BM aspirate sample may be taken at the same 
time for biomarker analysis. Additionally, collect blood plasma for 
 
analysis. 
24. The optional PD tissue sample should contain tumor cells, either BM aspirate 
clot, or other tissue in case of extramedullary disease. Samples will be 
submitted to central lab for BCMA analysis, any remaining bone marrow and/or 
tissue sample will be used for biomarker research. 
25. Informed consent for optional sub-studies (e.g. genetic research) must be 
obtained before collecting a sample. The sample will be collected at the first 
opportunity after a participant has met all eligibility requirements, before/ on 
C1D1 prior to infusion. If insufficient DNA was extracted, or the sample was 
damaged or otherwise could not be processed, the site may be requested to 
recollect the genetic sample where applicable. 
26. PK samples to be taken in all participants for belantamab mafodotin 
measurement on: 
Belantamab mafodotin Dose 1 (Cycle 1)  
• 
Day 1: at pre-infusion (within 30 min prior to SOI), EOI (0 to 15 min after 
EOI), at 2 h (15 min) after SOI and at 24h (± 2 h) after SOI. 
• 
Day 4 (i.e., 72 h after SOI [24 h]), one PK sample to be taken after ECG 
performed. 
• 
Day 8: at pre-infusion (within 30 min prior to Day 8 SOI), EOI (0 to 15 min 
after Day 8 EOI), at 2 h ( 15 min) after SOI and at 24h ( 2 h) after SOI. 
• 
Day 11: One PK sample to be taken after ECG performed 
• 
Day 15 through and including on Day 21:  One PK sample to be taken. 
Administration of 
lenalidomide30 
X 
X 
 
25 or 10 mg PO 
Days 1-21 of 
each 28-day 
cycle 
Administration of 
dexamethasone31 
X 
X 
 
40 or 20 mg on 
Days 1, 8, 15, 
and 22 of each 
28-day cycle 
Preservative-free artificial 
tears32 
X 
Cooling eye masks32 
X 
X 
 
X 
Venous Thrombo-Embolism 
(VTE) prophylaxis33 
X 
X 
X 
X 
 
Health Outcomes 
EORTC QLQ-C30 AND 
QLQ-MY2034 
X 
 
Every 8 
weeks 
starting at W9 
 
PRO-CTCAE34 
X 
 
X 
 
OSDI and NEI-VFQ-2534 
X 
 
X 
 
 
 
 
CCI
CCI


TMF-14624358 
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Protocol Amd 04 
 
50 
 
Study Assessments1 
Cycle 1  
Every 28 
Days 
 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm A belantamab mafodotin SPLIT dosing only) 
Day 12 
Day 8 
Belantamab mafodotin Dose 2  
• 
Day 1: at pre- infusion (within 30 min prior to SOI) and EOI (0 to 15 min 
after EOI).  
If Dose 2 is delayed, collect one PK sample on this day (Dose 1 Day 29) 
regardless of dosing. 
• 
Day 8: at pre- infusion (within 30 min prior to SOI) and EOI (0 to 15 min 
after EOI).  
Belantamab mafodotin Dose 3 
• 
Day 1: at pre- infusion (within 30 min prior to SOI) and EOI (0 to 15 min 
after EOI). 
• 
Day 8: at pre- infusion (within 30 min prior to SOI) and EOI (0 to 15 min 
after EOI). 
Belantamab mafodotin Dose 6  
• 
Day 1: at pre- infusion (within 30 min prior to SOI) and EOI (0 to 15 min 
after EOI). 
• 
Day 8: at pre- infusion (within 30 min prior to SOI) and EOI (0 to 15 min 
after EOI). 
Belantamab mafodotin Dose 9  
• 
Day 1 only: at pre- infusion (within 30 min prior to SOI). 
Belantamab mafodotin Dose 12 
• 
Day 1 only: at pre-infusion (within 30 min prior to SOI). 
For treatment beyond belantamab mafodotin Dose 12, pre-infusion samples will 
be collected on Day 1 only of every 6th Dose of belantamab mafodotin (Dose 18, 
Dose 24, Dose 30 and so on, until PD). 
samples will be collected every 
time a belantamab mafodotin PK sample is collected. See footnote 22. 
NOTE: All pre-dosing samples must be collected on D8 even if belantamab 
mafodotin dosing is delayed.  Any samples that are pre-dose but dose not 
administered should be moved to unscheduled.  If belantamab mafodotin 
CCI


TMF-14624358 
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Protocol Amd 04 
 
51 
 
Study Assessments1 
Cycle 1  
Every 28 
Days 
 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm A belantamab mafodotin SPLIT dosing only) 
Day 12 
Day 8 
D8 dosing is delayed and D8 PK sampling were planned for that dose, pre-
dose and EOI sample must be taken on the day of dosing.  
27. All ADA samples will be collected prior to each belantamab mafodotin infusion 
at Dose 1, 2, 3, 6, 9 and 12 (at the same time as the pre-infusion belantamab 
mafodotin PK samples are taken); for treatment beyond 12 cycles, collect 
samples for ADA analysis prior to each infusion every 6th Dose of belantamab 
mafodotin (Dose 18, Dose 24, Dose 30 etc. until PD). 
NOTE: ADA samples only apply to Day 1 dose, not the Day 8 dose. 
28. Premedication should be considered in any participant who experienced an IRR 
during the first or any subsequent infusion with belantamab mafodotin. 
29. Belantamab mafodotin will be administered first as a 30 min to 1 h infusion 
followed by 1-2 h rest period. For D1, a window of 3 days is acceptable for 
administration of study treatment after C1. For D8, belantamab mafodotin can 
be delayed and administered any time up to D15. Refer to Section 8.2 for dose 
modification guidance. Note: “SPLIT” Dosing Schedule: belantamab mafodotin 
will be split into two equal halves and each half dose will be administered on D1 
and D8 of each cycle. For example: A “2.5 mg/kg SPLIT” dosing schedule will 
administer a 1.25 mg/kg dose on D1 and a 1.25 mg/kg dose on D8 of each 
cycle. A “3.4 mg/kg SPLIT” dosing schedule will administer a 1.7 mg/kg dose on 
D1 and a 1.7 mg/kg dose on D8 of each cycle. 
NOTE: If the participant is unable to receive D1 dose, D8 dose must be 
withheld. If belantamab mafodotin was administered on D1, participant 
should always receive belantamab mafodotin on D8 of any SPLIT dosing 
cycle unless the investigator determines that the participant is clinically 
unfit to receive the dose (e.g., febrile neutropenia, active infection). 
30. Lenalidomide: 25 mg orally daily on Days 1 - 21 of each cycle in participants 
with >60 mL/min/1.73 m2, or reduced to 10 mg daily if the eGFR is 40-60 
mL/min/1.73 m2. [Please refer to lenalidomide PI]. Refer to Section 8.2 for dose 
modification guidance. 


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Protocol Amd 04 
 
52 
 
Study Assessments1 
Cycle 1  
Every 28 
Days 
 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm A belantamab mafodotin SPLIT dosing only) 
Day 12 
Day 8 
31. Dexamethasone: 40 mg weekly, orally on Days 1, 8, 15, 22 of each cycle, 
Participants who are >75y with BMI <18.5 kg/m2, the dose of dexamethasone 
can be reduced to 20 mg weekly. If intolerance to dexamethasone develops, 
dexamethasone may be reduced to 20 mg. If 20 mg is not tolerated, the 
dexamethasone dose can be further reduced or permanently discontinued. 
Please refer to Section 8.2 for dose modification guidance. 
On days where only lenalidomide and dexamethasone are taken at home, they 
should be taken in the morning approximately at the same time each day. On 
C1D1, lenalidomide should be administered as close as possible to the end of 
the 1-2 h rest period after administration of belantamab mafodotin and no later 
than 6 h after the end of the rest period after administration of belantamab 
mafodotin. On subsequent lenalidomide and belantamab mafodotin co-
administration days such as C2D1, C3D1 and thereafter, lenalidomide should 
be administered after the end of the 1-2 h rest period after administration of 
belantamab mafodotin. Participant Diary will be used to keep record of self-
administered oral study treatment(s) at home. 
32. Corneal Events Management (SPLIT Dose):  
- Prophylactic preservative-free artificial tears must be administered in each eye 
at least 4-8 times daily beginning on C1D1 until end of treatment. 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. 
- At the start of each infusion, participants may apply cooling eye masks for 
approximately 1 h or as long as tolerated. 
33. ASA or LMH or oral anticoagulants according to institutional guidance for the 
duration of treatment with lenalidomide. 
34. EORTC QLQ-C30 AND QLQ-MY20 will be collected every 8 weeks, and PRO-
CTCAE, OSDI and NEI-VFQ-25 will be collected every 4 weeks, even if cycle is 
delayed. Participants who cannot complete the self-administered version should 
use an Interviewer-Administered format. The interview may be administered 


TMF-14624358 
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207497 
 
Protocol Amd 04 
 
53 
 
Study Assessments1 
Cycle 1  
Every 28 
Days 
 
(Starting at 
Week 53 
regardless of 
dosing) 
Starting at 
Cycle 24 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm A belantamab mafodotin SPLIT dosing only) 
Day 12 
Day 8 
over the telephone. If the Interviewer-Administered format is used, it should be 
read to the participants verbatim, and participant responses should be recorded 
directly without any interpretation.  Refer to SRM for further details. 
 
Table 7 
Schedule of Activities - On Study Assessments for Arm B (belantamab mafodotin in combination with bortezomib 
plus dexamethasone) [21-Day Cycle] - belantamab mafodotin SINGLE Dosing Only 
Study Assessments1 
Cycle 1 
Every 21 
Days 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm B belantamab mafodotin SINGLE dosing only) 
Day 12 
D4, D8 
and 
D113 
ECOG Performance Status 
 
 
X 
 
1. 
All assessments apply to Part 1 and 2 of the study, unless stated otherwise. 
2. 
Screening Assessments do not need to be repeated on C1D1 unless 
otherwise specified. 
3. 
C1 D4, D8, and D11 are dosing days for bortezomib.  
4. 
All assessments starting at week 4 can be performed within 3 days prior to 
the scheduled date unless otherwise specified. 
5. 
Assessments scheduled on days of dosing should be done prior to drug 
administration, unless otherwise specified. Physical Exam must be within 72 h 
prior to 1st dose of study drugs to be administrated in that cycle. Body weight 
at C1D1 (prior to dosing) will be used for dose calculation of belantamab 
mafodotin.  Body weight to be measured prior to each dose. If the change of 
body weight is greater than 10%, the dose should be re-calculated based on 
Adverse Events/SAEs6 
X 
X 
Ongoing 
Ongoing 
Concomitant Medications 
X 
X 
Ongoing 
Ongoing 
 
Safety 
Physical Exam 
X 
 
X 
X5 
Ocular Exam7 
 
 
 
X 
Vital Signs (BP, Heart rate Body 
Temperature)8 
X 
X 
 
X 
(must also be 
done with each 
dose of 
bortezomib) 


TMF-14624358 
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54 
 
Study Assessments1 
Cycle 1 
Every 21 
Days 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm B belantamab mafodotin SINGLE dosing only) 
Day 12 
D4, D8 
and 
D113 
Body Weight (BW) and Height 
BW only 
 
 
BW only 
the actual body weight at the time of dosing. Up to 8 cycles of bortezomib and 
dexamethasone in combination with belantamab mafodotin are allowed; after 
the 8th cycle of Bor/Dex, participants will continue belantamab mafodotin 
monotherapy until progressive disease, intolerable AEs, or death occurs. 
6. 
Treatment-related toxicities will be assessed for at least 70 days after the last 
dose regardless initiation of new anticancer therapy. All related SAEs are to 
be collected from consent through 
 follow-up. For reporting of ocular 
events see the guidance provided in Appendix 8. 
7. 
Participants will be assessed by a qualified eye care specialist (Appendix 12) 
on Day 1 of every cycle prior to dosing up to Dose 6 of belantamab mafodotin 
(assessment window of up to 5 days prior to dosing, but all effort should be 
made to schedule as close to belantamab mafodotin dosing as possible). If 
there are no significant ocular examinations findings, patient’s symptoms or 
vision changes at the time of Dose 6 exam, participants may have their 
ophthalmologic exams decreased to once every 3 months. If a participant 
subsequently develops vision changes or other ocular symptoms, the 
participant should be promptly evaluated by a qualified eye care specialist. In 
case of persistent ophthalmic exam findings, newly developed ocular 
symptoms or vision changes at Dose 6 exam, the participants will have further 
ophthalmologic exams, at least every cycle until resolution (to Grade 1 or 
baseline) or more frequently as clinically indicated by the qualified eye care 
specialist. See Section 10.6.7.1 for full details of ocular exam procedures. 
8. 
On each belantamab mafodotin dosing day, vital signs must be assessed 
within 30 min prior to Start of Infusion (SOI), within 15 min after End of 
Infusion (EOI), and at 1 h (15 min) after EOI. On days where vital sign time 
points align with PK sampling time points, vital signs should be assessed prior 
to belantamab mafodotin PK samples being drawn. Vital signs must be 
Hematology9 
X 
X 
X 
X  
(must also be 
done with each 
dose of 
bortezomib) 
Clinical chemistry9 
X 
X 
X 
X 
HbA1c 
As clinically indicated 
C-reactive Protein (CRP) 9 
 
 
X 
 
Urinalysis (dipstick)9 
X 
 
X 
 
Estimated Glomerular Filtration 
Rate (eGFR) by MDRD formula 
X 
 
X 
 
Spot urine for 
albumin/creatinine ratio10 
 
 
X 
 
Pregnancy Test for WOCBP11 
X 
 
X 
X 
12-lead ECG12 
X 
X 
 
X 
ECHO – LVEF13 
 
 
Every 12 
weeks  
(At week 13, 
25, 37, 49 and 
so on) 
 
 
Disease Evaluation [every 3 weeks (3 days) even if the cycle is delayed]14 
SPEP (Serum Protein 
Electrophoresis) 
 
 
X 
 
Serum Kappa, lambda free LC, 
FLC ratio 
 
 
X 
 
CC
I


TMF-14624358 
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55 
 
Study Assessments1 
Cycle 1 
Every 21 
Days 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm B belantamab mafodotin SINGLE dosing only) 
Day 12 
D4, D8 
and 
D113 
Serum Immunofixation15 
 
 
At time of 
suspected CR 
then until 
suspected PD 
 
assessed within 30 mins before and within 15 min after each dose of 
bortezomib. 
9. 
Hematology and clinical chemistry must be repeated if not within 24 h prior to 
1st dose of study drugs to be administrated in that cycle. Hematology must 
be repeated prior to each dose of bortezomib. Starting at C9, Hematology 
must be repeated prior to each dose of belantamab mafodotin. An additional 
hematology sample must be collected on D15 24 h for Cycles 1-8. On Day 1 
of any planned cycle, Absolute Neutrophil Count (ANC) must be ≥1.0×109/L 
to administer treatment. Refer to Table 27 for comprehensive list of lab tests. 
10. Albumin/creatinine ratio (Spot urine from first void) every 3 weeks 3 days 
(local lab, if local not available then central). 
11. Perform only in women of childbearing potential (WOCBP). A serum 
pregnancy test must be performed at screening; if the test is completed within 
72 hours prior to the first dose of belantamab mafodotin, this assessment 
does not have to be repeated on C1D1. For questionable cases, follicle-
stimulating hormone (FSH) and estradiol (as needed in WOCBP) should be 
performed at local lab to determine childbearing potential. WOCBP must have 
a negative highly sensitive serum pregnancy test within 72 hours of dosing on 
C1D1. Subsequent pregnancy test on dosing days may be either serum or 
urine test.  Each pregnancy test must be performed within 24 h prior to 
dosing.  
12. SINGLE ECG performed pre-infusion on belantamab mafodotin dosing days.  
UPEP (Urine Protein 
Electrophoresis) 
(on 24 h collected urine) 
 
 
X 
 
Urine Immunofixation15 
 
 
At time of 
suspected CR 
then until 
suspected PD 
 
Ca corrected for Albumin 
(Serum) 
 
 
X 
 
IgG, IgM, IgA 
 
 
X 
 
IgD/IgE16 
 
 
X 
 
Imaging for extramedullary 
disease17 
 
 
Week 13, 25, 
37, 49 and 
then if 
clinically 
indicated 
 
Skeletal Survey18 
 
 
As clinically 
indicated 
 


TMF-14624358 
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Protocol Amd 04 
 
56 
 
Study Assessments1 
Cycle 1 
Every 21 
Days 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm B belantamab mafodotin SINGLE dosing only) 
Day 12 
D4, D8 
and 
D113 
Whole body PET/CT 
 
 
Only once at 
time of 
achieving CR 
or sCR 
(whichever 
comes first) 
according to 
IMWG 2016 
 
On days when belantamab mafodotin PK sampling is performed, PK samples 
should be drawn shortly after ECG.  TRIPLICATE ECGs will be performed as 
described below with SINGLE ECG performed at all other times.  All ECGs 
will be collected centrally (refer to SRM for details). 
Belantamab mafodotin Dose 1 (C1)  
D1: TRIPLICATE ECGs Pre-infusion (within 30 min prior to SOI), EOI (up to 
15 min after EOI), 2 h (±15 min) after SOI and 24 h (±2 h) after SOI.  
D4: TRIPLICATE ECG performed before PK sample. 
D11: TRIPLICATE ECG performed before PK sample. 
Belantamab mafodotin Dose 2  
D1: SINGLE ECG pre-infusion  
Belantamab mafodotin Dose 3  
D1: TRIPLICATE ECGs pre-infusion (within 30 min prior to SOI), and EOI (up 
to 15 min after EOI). 
D4: TRIPLICATE ECG performed before PK sample. 
D11: TRIPLICATE ECG performed before PK sample. 
13. ECHO will be performed every 12 weeks (7 days) and locally.  
14. Disease evaluation (except imaging and skeletal survey) will continue to be 
performed, every 3 weeks (3 days) even if the cycle is delayed. 
15. At time of first achieving SPEP or Urine M protein ~0 g/dl (suspected CR) and 
until suspected PD after CR or stringent Complete Response (sCR). 
16. Only in participants with IgD/IgE myeloma  
17. Imaging is only required for participants with extramedullary disease at week 
13, 25, 37, 49 (±7 days) and then if clinically indicated by either CT, MRI, or 
PET/CT per local guidance. Needs to be performed by the same method 
throughout the study as was done at baseline (i.e., if CT/PET scan was used 
as baseline, participant needs to be followed by CT/PET scans).  Selected 
target lesion needs to be measured and followed over time. Plasmacytoma 
Response assessment by 
IMWG19 
 
 
X 
 
 
Bone Marrow Tests 
BM aspirate/biopsy for Disease 
Assessment20,24 
 
 
At time of 
suspected CR 
or at time of 
suspected PD 
(only if PD not 
evident 
otherwise) 
 
BM biopsy to confirm sCR by 
IHC 
 
 
Upon 
achieving CR 
 
BM aspirate for 
 
 testing21   
 
 
At time of first 
achieving 
VGPR or 
better 
 
 
Biomarkers 
 
X 
 
 
X 
CCI
CCI


TMF-14624358 
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57 
 
Study Assessments1 
Cycle 1 
Every 21 
Days 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm B belantamab mafodotin SINGLE dosing only) 
Day 12 
D4, D8 
and 
D113 
 
X 
 
At time of 
achieving 
VGPR or 
better21 
 
measurements should be taken from the CT portion of the PET/CT, or MRI 
scans, or dedicated CT scans where applicable. 
For participants with only skin involvement, skin lesions should be measured 
with a ruler.  Measurement of tumor size will be determined by the Sum of the 
Products of the maximal perpendicular diameters of measured lesions (SPD).  
18. Imaging of bones for lytic lesions by method aligned with institutional 
guidance (X-ray, CT or MRI). Survey results within 30 days prior to C1D1 date 
are acceptable. At later cycles, repeat as clinically indicated, or if worsening 
clinical symptoms suggest PD, by the same method used as at screening. 
19. Response to treatment will be assessed every 3 weeks (3 days), based on 
laboratory tests and imaging (if applicable), using IMWG criteria [Kumar, 
2016]. 
20. Whenever CR is assessed, if possible, a further BM aspirate sample may be 
taken at the same time for biomarker analysis. 
21. 
) to be performed by the central lab at the time 
of first achieving VGPR or better. Thereafter, 
 should be repeated 
every 6 months until PD or CR. In case of deepening of response from VGPR 
to CR, or achieving CR without prior VGPR, 
 should be 
performed at the time of achieving suspected CR and repeated every 6 
months until PD. Whenever possible, a further BM aspirate sample may be 
taken at the same time for biomarker analysis. Additionally, collect blood 
plasma for 
analysis. 
 
Optional  
Optional tissue sample at PD 
for BCMA expression and 
biomarker research24 
 
 
X 
 
Genetic sample25 
X 
 
 
 
 
PK and ADA 
Pharmacokinetic blood 
sampling for belantamab 
mafodotin22,26 
X26 
 
 
X (at selected 
cycles)26 
Pharmacokinetic blood 
sampling for bortezomib27  
X27 
 
 
 
Anti-drug antibodies (ADA)28 
X28 
 
 
X (at selected 
cycles)28 
 
Treatment 
Premedication if needed29 
X 
 
 
X 
Administration of belantamab 
mafodotin30 
X 
 
 
Day 1 of each 
21-day cycle 
CCI
CCI
CCI
CCI
CCI
CCI


TMF-14624358 
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Protocol Amd 04 
 
58 
 
Study Assessments1 
Cycle 1 
Every 21 
Days 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm B belantamab mafodotin SINGLE dosing only) 
Day 12 
D4, D8 
and 
D113 
Administration of bortezomib31 
X 
1.3 
mg/m2 
SC or IV 
on Days 
1, 4, 8 
and 11 of 
each 21-
day cycle 
 
1.3 mg/m2 SC or 
IV on Days 1, 4, 
8 and 11 of each 
21-day cycle 
24. The optional PD tissue sample should contain tumor cells, either BM aspirate 
clot, or other tissue in case of extramedullary disease. Samples will be 
submitted to central lab for BCMA analysis, any remaining bone marrow 
and/or tissue sample will be used for biomarker research. 
25. Informed consent for optional sub-studies (e.g. genetic research) must be 
obtained before collecting a sample. The sample will be collected at the first 
opportunity after a participant has met all eligibility requirements, before/ on 
C1D1 prior to infusion. If insufficient DNA was extracted, or the sample was 
damaged or otherwise could not be processed, the site may be requested to 
recollect the genetic sample where applicable. 
26. PK samples to be taken in all participants for belantamab mafodotin 
measurement on: 
Belantamab mafodotin Dose 1 (Cycle 1)  
Day 1: at pre-infusion (within 30 min prior to SOI, EOI (0 to 15 min after EOI), 
at 2 h (± 15 min) after SOI and 24h (±2 h) after SOI.  
Day 4: one PK sample to be taken prior to Bor/Dex administration 
Day 11: one PK sample to be taken prior to Bor/Dex administration 
Belantamab mafodotin Dose 2  
Day 1: at pre-infusion (within 30 min prior to SOI) and EOI (0 to 15 min after 
EOI).  
If Dose 2 is delayed, collect one PK sample on this day (Dose 1 Day 22) 
regardless of dosing. 
Belantamab mafodotin Dose 3  
Day 1: at pre-infusion (within 30 min prior to SOI) and EOI (0 to 15 min after 
EOI),  
Day 4: during visit to be taken prior to Bor/Dex administration 
Day 11: during visit to be taken prior to Bor/Dex administration  
Administration of 
dexamethasone32 
X 
20 mg 
PO or IV 
on Days 
1, 2, 4, 5, 
8, 9, 11, 
and 12 of 
each 21-
day cycle 
 
20 mg PO or IV 
on Days 1, 2, 4, 
5, 8, 9, 11, and 
12 of each 21-
day cycle 
Preservative-free artificial 
tears33 
X 
Cooling eye masks33 
X 
 
 
X 
Antiviral prophylaxis34 
X 
 
Health Outcomes 
EORTC QLQ-C30 AND QLQ-
MY20 (Part 1 and Part 2)35 
X 
 
Every 6 
weeks starting 
at W7 
 
PRO-CTCAE35 
X 
 
X 
 
OSDI and NEI-VFQ-2535 
X 
 
X 
 


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59 
 
Study Assessments1 
Cycle 1 
Every 21 
Days 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm B belantamab mafodotin SINGLE dosing only) 
Day 12 
D4, D8 
and 
D113 
 
 
 
 
 
 
 
 
 
 
 
 
 
Belantamab mafodotin Dose 6  
Day 1: at pre-infusion (within 30 min prior to SOI) and EOI (0 to 15 min after 
EOI) 
Belantamab mafodotin Dose 9: 
Day 1: at pre-infusion (within 30 min prior to SOI) 
Belantamab mafodotin Dose 12: 
Day 1: at pre-infusion (within 30 min prior to SOI). 
For treatment beyond belantamab mafodotin Dose 12, pre-infusion samples 
will be collected every 6th Dose of belantamab mafodotin (Dose18, Dose24, 
Dose30 and so on, until PD).
 samples will be collected every time a 
belantamab mafodotin PK sample is collected. See footnote 22.   
27. Bortezomib PK sampling after the first bortezomib dose in C1:  
Serial PK samples will be collected at pre-dose (within 30 min prior to 
administration) and, after the administration of bortezomib at 5 (± 1 min), 15 
(± 1 min), and 30 (±2 min) min,1 h (±5 min), 2 h (±5 min), 4 h (±5 min), 6 h 
(±5 min), 10 h (±2 h), 24 h (±2 h), 48 h (±2 h), and 72 h (± 2 h).The 72 h 
sample needs to be taken prior to bortezomib dosing on D4. 
28. All ADA samples will be collected prior to each belantamab mafodotin infusion 
(at Dose 1 (C1) D1, Dose 2, 3, 6, 9 and 12) both in Part 1 and Part 2 (at the 
same time as the pre-infusion belantamab mafodotin PK samples are taken); 
for treatment beyond 12 cycles, collect samples for ADA analysis prior to 
each infusion every 6th Dose of belantamab mafodotin (Dose 18, Dose 24, 
Dose 30 and so on, until PD). 
29. Premedication should be considered in any participant who experienced an 
IRR during the first or any subsequent infusions with belantamab mafodotin. 
30. Belantamab mafodotin will be administered first as a 30 min to 1 h infusion, 
followed by 1-2 h rest period. A window of 3 days is acceptable for 
administration of study treatment after C1. Please refer to Section 8.2 for 
CCI


TMF-14624358 
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Protocol Amd 04 
 
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Study Assessments1 
Cycle 1 
Every 21 
Days 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm B belantamab mafodotin SINGLE dosing only) 
Day 12 
D4, D8 
and 
D113 
 
 
 
 
 
 
 
 
 
 
 
 
 
dose modification guidance.  Note: “SINGLE” Dosing Schedule: belantamab 
mafodotin will be administered as a SINGLE full dose on Day 1 of each cycle. 
For example: A “2.5 mg/kg SINGLE” dosing schedule of belantamab 
mafodotin will administer a 2.5 mg/kg dose on D1 of each cycle. A “3.4 mg/kg 
SINGLE” dosing schedule will administer a 3.4 mg/kg dose on D1 of each 
cycle. 
31. Bortezomib 1.3 mg/m2 SC or IV (depending on participants’ and institutional 
preference) on Days 1, 4, 8, and 11 of every 21-day cycle for a total up to 8 
cycles. Please refer to Section 8.2 for dose modification guidance. 
         Note: Participants will receive antiviral prophylaxis (for example acyclovir or 
other according to the institutional guidelines), for the entire duration of 
treatment with Bor/Dex (8 cycles). 
32. Dexamethasone 20 mg PO or IV will be given on Days 1, 2, 4, 5, 8, 9, 11, and 
12 of every 21-day cycle. Dexamethasone will be given for a total of up to 8 
cycles.  If dexamethasone is taken at home, it should be taken approximately 
at the same time each day. Participant Diary will be used to keep record of 
self-administer oral dexamethasone at home. Participants who are >75y with 
BMI <18.5 kg/m2, the dose of dexamethasone can be reduced to 10 mg. If 
intolerance to dexamethasone develops, dexamethasone may be reduced to 
10 mg. If 10 mg is not tolerated, the dexamethasone dose can be further 
reduced or permanently discontinued. Please refer to Section 8.2 for dose 
modification guidance. 
33. Corneal Events Management:  
        - Prophylactic preservative-free artificial tears must be administered in each 
eye at least 4-8 times daily beginning on C1D1 until end of treatment. 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. 


TMF-14624358 
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Protocol Amd 04 
 
61 
 
Study Assessments1 
Cycle 1 
Every 21 
Days 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes (Arm B belantamab mafodotin SINGLE dosing only) 
Day 12 
D4, D8 
and 
D113 
 
 
 
 
 
- At the start of each infusion, participants may apply cooling eye masks for 
approximately 1 h or as long as tolerated. 
34. Antiviral prophylaxis (for example acyclovir or other according to institutional 
guidelines) is required for the duration of bortezomib treatment.   
35. EORTC QLQ-C30 AND QLQ-MY20 will be collected every 6 weeks, and 
PRO-CTCAE, OSDI and NEI-VFQ-25 will be collected every 3 weeks, even if 
cycle is delayed. Participants who cannot complete the self-administered 
version should use an Interviewer-Administered format. The interview may be 
administered over the telephone. If the Interviewer-Administered format is 
used, it should be read to the participants verbatim, and participant responses 
should be recorded directly without any interpretation.  Refer to SRM for 
further details. 
 
Table 8 
Schedule of Activities - On Study Assessments for Arm B (belantamab mafodotin in combination with bortezomib 
plus dexamethasone) [21-Day Cycle] – belantamab mafodotin SPLIT Dosing Only  
Study Assessments1 
Cycle 1  
Every 21 
Days 
 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
 
Notes (Arm B belantamab mafodotin SPLIT dosing only) 
Day 12 
D4, D8 
and 
D113 
ECOG Performance Status 
 
 
X 
 
1. 
All assessments apply to Part 1 and 2 of the study unless stated otherwise.  
2. 
Screening Assessments do not need to be repeated on C1D1 unless 
otherwise specified. 
3. 
C1 D4, D8, and D11 are dosing days for bortezomib.  
Adverse Events/SAEs6 
X 
X 
Ongoing 
Ongoing 
Concomitant Medications 
X 
X 
Ongoing 
Ongoing 
 


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Protocol Amd 04 
 
62 
 
Study Assessments1 
Cycle 1  
Every 21 
Days 
 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
 
Notes (Arm B belantamab mafodotin SPLIT dosing only) 
Day 12 
D4, D8 
and 
D113 
Safety 
4. 
All assessments starting at week 4 can be performed within 3 days prior to 
the scheduled date unless otherwise specified.  
5. 
Assessments scheduled on days of dosing should be done prior to drug 
administration, unless otherwise specified. Physical Exam must be within 72 h 
prior to 1st dose of study drugs to be administrated in that cycle. Body weight 
at C1D1 (prior to dosing) will be used for dose calculation of belantamab 
mafodotin.  Body weight to be measured prior to each dose. If the change of 
body weight is greater than 10%, the dose should be re-calculated based on 
the actual body weight at the time of dosing. Up to 8 cycles of bortezomib and 
dexamethasone in combination with belantamab mafodotin are allowed; after 
8 cycles of Bor/Dex, participants will be allowed to continue on belantamab 
mafodotin monotherapy until progressive disease, intolerable AEs, or death 
occurs. 
6. 
Treatment-related toxicities will be assessed for at least 70 days after the last 
dose regardless initiation of new anticancer therapy. All related SAEs are to 
be collected from consent through
follow-up. For reporting of ocular 
events see the guidance provided in Appendix 8. 
7. 
Participants will be assessed by a qualified eye care specialist (Appendix 12) 
on Day 1 of every cycle prior to dosing up to Dose 6 of belantamab mafodotin 
(assessment window of up to 5 days prior to dosing, but all effort should be 
made to schedule as close to belantamab mafodotin dosing as possible). If 
there are no significant ocular examinations findings, patient’s symptoms or 
vision changes at the time of Dose 6 exam, participants may have their 
ophthalmologic exams decreased to once every 3 months. If a participant 
subsequently develops vision changes or other ocular symptoms, the 
participant should be promptly evaluated by a qualified eye care specialist. In 
case of persistent ophthalmic exam findings, newly developed ocular 
Physical Exam 
X 
X (Day 8 
only) 
X 
X5 
Ocular Exam7 
 
 
 
X 
Vital Signs (BP, Heart rate Body 
Temperature)8 
X 
X 
 
X 
(must also be 
done with each 
dose of 
Bortezomib) 
Body Weight (BW) and Height 
BW only 
 
 
BW only 
Hematology9 
X 
X 
X 
X  
(must also be 
done with each 
dose of 
Bortezomib) 
Clinical chemistry9 
X 
X 
X 
X 
HbA1c 
As clinically indicated 
C-reactive Protein (CRP) 9 
 
 
X 
 
Urinalysis (dipstick)9 
X 
 
X 
 
Estimated Glomerular Filtration 
Rate (eGFR) by MDRD formula 
X 
 
X 
 
Spot urine for 
albumin/creatinine ratio10 
 
 
X 
 
Pregnancy Test for WOCBP11 
X 
 
X 
X 
12-lead ECG12 
X 
X 
 
X 
ECHO – LVEF13 
 
 
Every 12 
weeks  
 
CCI


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Protocol Amd 04 
 
63 
 
Study Assessments1 
Cycle 1  
Every 21 
Days 
 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
 
Notes (Arm B belantamab mafodotin SPLIT dosing only) 
Day 12 
D4, D8 
and 
D113 
(At week 13, 
25, 37, 49 and 
so on) 
symptoms or vision changes at Dose 6 exam, the participants will have further 
ophthalmologic exams, at least every cycle until resolution (to Grade 1 or 
baseline) or more frequently as clinically indicated by the qualified eye care 
specialist. See Section 10.6.7.1 for full details of ocular exam procedures. 
8. 
On each belantamab mafodotin dosing day, vital signs must be assessed 
within 30 min prior to Start of Infusion (SOI), within 15 min after End of 
Infusion (EOI), and at 1 h (±15 min) after EOI.  On days where vital sign time 
points align with PK sampling time points, vital signs should be assessed prior 
to belantamab mafodotin PK samples being drawn. Vital signs must be 
assessed within 30 mins before and within 15 min after each dose of 
bortezomib. 
9. 
Hematology and clinical chemistry must be repeated if not within 24 h prior to 
1st dose of study drugs to be administered in that cycle. Hematology must be 
repeated prior to each dose of bortezomib. Starting at C9, Hematology 
must be repeated prior to each dose of belantamab mafodotin. An additional 
hematology sample must be collected on Day 15 24 h for Cycles 1-8. On 
Day 1 of any planned cycle, Absolute Neutrophil Count (ANC) must be 
≥1.0×109/L to administer treatment. Refer to Table 27 for comprehensive list 
of lab tests.   
10. Albumin/creatinine ratio (Spot urine from first void) every 3 weeks 3 days 
(local lab, if local not available then central). 
11. Perform only in women of childbearing potential (WOCBP). A serum 
pregnancy test must be performed at screening; if the test is completed within 
72 hours prior to the first dose of belantamab mafodotin, this assessment 
does not have to be repeated on C1D1. For questionable cases, follicle-
stimulating hormone (FSH) and estradiol (as needed in WOCBP) should be 
performed at local lab to determine childbearing potential. WOCBP must have 
 
Disease Evaluation [every 3 weeks (3 days) even if the cycle is delayed]14 
SPEP (Serum Protein 
Electrophoresis) 
 
 
X 
 
Serum Kappa, lambda free LC, 
FLC ratio 
 
 
X 
 
Serum Immunofixation15 
 
 
At time of 
suspected CR 
then until 
suspected PD 
 
UPEP (Urine Protein 
Electrophoresis) 
(on 24 h collected urine) 
 
 
X 
 
Urine Immunofixation15 
 
 
At time of 
suspected CR 
then until 
suspected PD 
 
Ca corrected for Albumin 
(Serum) 
 
 
X 
 
IgG, IgM, IgA 
 
 
X 
 
IgD/IgE16 
 
 
X 
 
Imaging for extramedullary 
disease17 
 
 
Week 13, 25, 
37, 49 and 
then if 
 


TMF-14624358 
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Protocol Amd 04 
 
64 
 
Study Assessments1 
Cycle 1  
Every 21 
Days 
 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
 
Notes (Arm B belantamab mafodotin SPLIT dosing only) 
Day 12 
D4, D8 
and 
D113 
clinically 
indicated 
a negative highly sensitive serum pregnancy test within 72 hours of dosing on 
C1D1. Subsequent pregnancy test on dosing days may be either serum or 
urine test. Each pregnancy test must be performed within 24 h prior to dosing.  
12. SINGLE ECG performed pre-infusion on belantamab mafodotin dosing days.  
On days when belantamab mafodotin PK sampling is performed, ECGs 
should be performed prior to PK samples being drawn. TRIPLICATE ECGs 
will be performed as described below with SINGLE ECG performed at all 
other times.  All ECGs will be collected centrally (refer to SRM for details). 
Belantamab mafodotin Dose 1 (C1)  
Day 1: TRIPLICATE ECGs Pre-infusion (within 30 min prior to SOI), EOI (up 
to 15 min after EOI), 2 h (±15 min) after SOI and 24 h (±2 h) after SOI.  
Day 4: TRIPLICATE ECG performed before PK sample. 
Day 8: TRIPLICATE ECGs Pre-infusion (within 30 min prior to SOI), EOI (up 
to 15 min after EOI), 2 h (±15 min) after SOI and 24 h (±2 h) after SOI.  
Day 11: TRIPLICATE ECG performed before PK sample. 
Belantamab mafodotin Dose 2  
D1: SINGLE ECG pre-infusion 
D8: SINGLE ECG pre-infusion 
Belantamab mafodotin Dose 3  
D1: TRIPLICATE ECGs pre-infusion (within 30 min prior to SOI), EOI (up to 
15 min after EOI). 
D4: TRIPLICATE ECG performed before PK sample. 
D8: TRIPLICATE ECGs pre-infusion (within 30 min prior to SOI), EOI (up to 
15 min after EOI). 
D11: TRIPLICATE ECG performed before PK sample. 
13. ECHO will be performed every 12 weeks (7 days) and locally.  
14. Disease evaluation (except imaging and skeletal survey) will continue to be 
performed, every 3 weeks (3 days) even if the cycle is delayed. 
Skeletal Survey18 
 
 
As clinically 
indicated 
 
Whole body PET/CT 
 
 
Only once at 
time of 
achieving CR 
or sCR 
(whichever 
comes first) 
according to 
IMWG 2016 
 
Response assessment by 
IMWG19 
 
 
X 
 
 
Bone Marrow Tests 
BM aspirate/biopsy for Disease 
Assessment20,24 
 
 
At time of 
suspected CR 
or at time of 
suspected PD 
(only if PD not 
evident 
otherwise) 
 
BM biopsy to confirm sCR by 
IHC 
 
 
Upon 
achieving CR 
 
BM aspirate for 
 
 testing21   
 
 
At time of first 
achieving 
VGPR or 
better 
 
CCI


TMF-14624358 
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Protocol Amd 04 
 
65 
 
Study Assessments1 
Cycle 1  
Every 21 
Days 
 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
 
Notes (Arm B belantamab mafodotin SPLIT dosing only) 
Day 12 
D4, D8 
and 
D113 
 
15. At time of first achieving SPEP or Urine M protein ~0 g/dl (suspected CR) and 
until suspected PD after CR or stringent Complete Response (sCR). 
16. Only in participants with IgD/IgE myeloma  
17. Imaging is only required for participants with extramedullary disease at week 
13, 25, 37, 49 (±7 days) and then if clinically indicated by either CT, MRI, or 
PET/CT per local guidance. Needs to be performed by the same method 
throughout the study as was done at baseline (i.e., if CT/PET scan was used 
as baseline, participant needs to be followed by CT/PET scans).  Selected 
target lesion needs to be measured and followed over time. Plasmacytoma 
measurements should be taken from the CT portion of the PET/CT, or MRI 
scans, or dedicated CT scans where applicable. 
For participants with only skin involvement, skin lesions should be measured 
with a ruler.  Measurement of tumor size will be determined by the Sum of the 
Products of the maximal perpendicular diameters of measured lesions (SPD).  
18. Imaging of bones for lytic lesions by method aligned with institutional 
guidance (X-ray, CT or MRI). Survey results within 30 days prior to C1D1 date 
are acceptable. At later cycles, repeat as clinically indicated, or if worsening 
clinical symptoms suggest PD, by the same method used as at screening. 
19. Response to treatment will be assessed every 3 weeks (3 days), based on 
laboratory tests and imaging (if applicable), using IMWG criteria [Kumar, 
2016]. 
20. Whenever CR is assessed, if possible, a further BM aspirate sample may be 
taken at the same time for biomarker analysis. 
21. 
) to be performed by the central lab at the time 
of first achieving VGPR or better. Thereafter, 
 should be repeated 
every 6 months until PD or CR. In case of deepening of response from VGPR 
to CR, or achieving CR without prior VGPR, 
 should be 
performed at the time of achieving suspected CR and repeated every 6 
Biomarkers 
X 
 
 
X 
X 
 
At time of 
achieving 
VGPR or 
better21 
 
 
Optional  
Optional tissue sample at PD 
for BCMA expression and 
biomarker research24 
 
 
X 
 
Genetic sample23 
X 
 
 
 
 
PK and ADA 
Pharmacokinetic blood 
sampling for belantamab 
mafodotin22,26 
X26 
X (Day 
8)26 
 
X (at selected 
cycles)26 
 
 
 
 
 
Anti-drug antibodies (ADA)27 
X27 
 
 
X (at selected 
cycles)27 
 
Treatment 
Premedication if needed28 
X 
X 
 
X 
Administration of belantamab 
mafodotin29 
X 
X (Day 
8) 
 
Day 1 and Day 8 
of each 21-day 
cycle 
CCI
CCI
CCI
CCI


TMF-14624358 
CONFIDENTIAL 
 
 
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Protocol Amd 04 
 
66 
 
Study Assessments1 
Cycle 1  
Every 21 
Days 
 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
 
Notes (Arm B belantamab mafodotin SPLIT dosing only) 
Day 12 
D4, D8 
and 
D113 
Administration of bortezomib30 
X 
1.3 
mg/m2 
SC or IV 
on Days 
1, 4, 8 
and 11 of 
each 21-
day cycle 
 
1.3 mg/m2 SC or 
IV on Days 1, 4, 
8 and 11 of each 
21-day cycle 
months until PD.  Whenever possible, a further BM aspirate sample may be 
taken at the same time for biomarker analysis. Additionally, collect blood 
plasma for 
 analysis.   
24. The optional PD tissue sample should contain tumor cells, either BM aspirate 
clot, or other tissue in case of extramedullary disease. Samples will be 
submitted to central lab for BCMA analysis, any remaining bone marrow 
and/or tissue sample will be used for biomarker research. 
25. Informed consent for optional sub-studies (e.g. genetic research) must be 
obtained before collecting a sample. The sample will be collected at the first 
opportunity after a participant has met all eligibility requirements, before/ on 
C1D1 prior to infusion. If insufficient DNA was extracted, or the sample was 
damaged or otherwise could not be processed, the site may be requested to 
recollect the genetic sample where applicable.  
26. PK samples to be taken in all participants for belantamab mafodotin 
measurement on: 
Belantamab mafodotin Dose 1 (C1)  
• 
Day 1: at pre-infusion (within 30 min prior to SOI), End of Infusion (up 
to 15 min after EOI), at 2 h (± 15 min) after SOI and 24h (±2 h) after 
SOI.  
• 
Day 4: one PK sample to be taken prior to Bor/Dex administration 
• 
Day 8: at pre-infusion (within 30 min prior to SOI), End of Infusion (up 
to 15 min after EOI), at 2 h (± 15 min) after SOI and 24h (±2 h) after 
SOI.  
• 
Day 11: one PK sample to be taken prior to Bor/Dex administration 
Belantamab mafodotin Dose 2  
Administration of 
dexamethasone31 
X 
20 mg 
PO or IV 
on Days 
1, 2, 4, 5, 
8, 9, 11, 
and 12 of 
each 21-
day cycle 
 
20 mg PO or IV 
on Days 1, 2, 4, 
5, 8, 9, 11, and 
12 of each 21-
day cycle 
Preservative-free artificial 
tears32 
X 
Cooling eye masks32 
X 
X (Day 
8) 
 
X 
Antiviral prophylaxis33 
X 
 
Health Outcomes 
EORTC QLQ-C30 AND QLQ-
MY20 (Part 1 and Part 2)34 
X 
 
Every 6 
weeks starting 
at W7 
 
PRO-CTCAE34 
X 
 
X 
 
OSDI and NEI-VFQ-2534 
X 
 
X 
 
CCI
CCI


TMF-14624358 
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Protocol Amd 04 
 
67 
 
Study Assessments1 
Cycle 1  
Every 21 
Days 
 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
 
Notes (Arm B belantamab mafodotin SPLIT dosing only) 
Day 12 
D4, D8 
and 
D113 
 
 
 
 
 
 
 
 
 
 
 
 
 
• 
Day 1: at pre-infusion (within 30 min prior to SOI) and EOI (up to 15 
min after EOI).  
• 
If Dose 2 is delayed, collect one PK sample on this day (Dose 1 D22) 
regardless of dosing. 
Belantamab mafodotin Dose 3  
• 
Day 1: at pre-infusion (within 30 min prior to SOI) and EOI (up to 15 
min after EOI),  
• 
Day 4: during visit to be taken prior to Bor/Dex administration 
• 
Day 8: at pre-infusion (within 30 min prior to SOI) and EOI (up to 15 
min after EOI),  
• 
Day 11: during visit to be taken prior to Bor/Dex administration 
Belantamab mafodotin Dose 6  
• 
Day 1: at pre-infusion (within 30 min prior to SOI) and EOI (up to 15 
min after EOI) 
Belantamab mafodotin Dose 9  
• 
Day 1: at pre-infusion (within 30 min prior to SOI) 
Belantamab mafodotin Dose 12  
• 
Day 1: at pre-infusion (within 30 min prior to SOI). 
For treatment beyond belantamab mafodotin Dose 12, pre-infusion samples 
will be collected every 6th Dose of belantamab mafodotin (Dose 18, Dose 24, 
Dose 30 and so on, until PD). 
 samples will be collected every time a 
belantamab mafodotin PK sample is collected. See footnote 22. 
NOTE: All pre-dosing samples must be collected on D8 even if 
belantamab mafodotin dosing is delayed.  Any samples that are pre-
dose but dose not administered should be moved to unscheduled.  If 
belantamab mafodotin D8 dosing is delayed and D8 PK sampling were 
planned for that dose, pre-dose and EOI sample must be taken on the 
day of dosing.  
CCI


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Study Assessments1 
Cycle 1  
Every 21 
Days 
 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
 
Notes (Arm B belantamab mafodotin SPLIT dosing only) 
Day 12 
D4, D8 
and 
D113 
27. All ADA samples will be collected prior to each belantamab mafodotin infusion 
(at Dose 1 (C1) Dose 2, 3, 6, 9 and 12) (at the same time as the pre-infusion 
belantamab mafodotin PK samples are taken); for treatment beyond 12 
cycles, collect samples for ADA analysis prior to each infusion every 6th Dose 
of belantamab mafodotin ( and so on, until PD). 
NOTE: ADA samples only apply to Day 1 dose, not the Day 8 dose. 
28. Premedication should be considered in any participant who experienced an 
IRR during the first or any subsequent infusions with belantamab mafodotin. 
29. Belantamab mafodotin administration: belantamab mafodotin will be 
administered first as a 30 min to 1 h infusion, followed by 1-2 h rest period. 
For D1, a window of 3 days is acceptable for administration of study 
treatment after C1. For D8, belantamab mafodotin can be delayed and 
administered any time up to D15. Please refer to Section 8.2 for dose 
modification guidance. Note: “SPLIT” Dosing Schedule: belantamab 
mafodotin will be split into two equal halves and each half dose will be 
administered on D1 and D8 of each cycle. For example: A “2.5 mg/kg SPLIT” 
dosing schedule will administer a 1.25 mg/kg dose on D1 and a 1.25 mg/kg 
dose on D8 of each cycle. A “3.4 mg/kg SPLIT” dosing schedule will 
administer a 1.7 mg/kg dose on Day 1 and a 1.7 mg/kg dose on D8 of each 
cycle. 
NOTE: If the participant is unable to receive Day 1 dose, D8 dose must 
be withheld. If belantamab mafodotin was administered on D1, 
participant should always receive belantamab mafodotin on D8 of any 
SPLIT dosing cycle unless the investigator determines that the 
participant is clinically unfit to receive the dose (e.g., febrile 
neutropenia, active infection).  
30. Bortezomib 1.3 mg/m2 SC or IV (depending on participants’ and institutional 
preference) on Days 1, 4, 8, and 11 of every 21-day cycle for a total up to 8 
cycles. Please refer to Section 8.2 for instructions on dose delays. 


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Study Assessments1 
Cycle 1  
Every 21 
Days 
 
(Starting at 
Week 44 
regardless of 
dosing) 
 
Starting at 
Cycle 25 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
 
Notes (Arm B belantamab mafodotin SPLIT dosing only) 
Day 12 
D4, D8 
and 
D113 
Note: Participants will receive antiviral prophylaxis (for example acyclovir or 
other according to the institutional guidelines), for the entire duration of 
treatment with Bor/Dex (8 cycles). 
31. Dexamethasone 20 mg PO or IV will be given on Days 1, 2, 4, 5, 8, 9, 11, and 
12 of every 21-day cycle. Dexamethasone will be given for a total of up to 8 
cycles.  If dexamethasone is taken at home, it should be taken approximately 
at the same time each day. Participant Diary will be used to keep record of 
self-administer oral dexamethasone at home. Participants who are >75y with 
BMI <18.5 kg/m2, the dose of dexamethasone can be reduced to 10 mg. If 
intolerance to dexamethasone develops, dexamethasone may be reduced to 
10mg. If 10mg is not tolerated, the dexamethasone dose can be further 
reduced or permanently discontinued. [Please refer to Section 8.2 for details]. 
32. Corneal Events Management:  
        - Prophylactic preservative-free artificial tears must be administered in each 
eye at least 4-8 times daily beginning on C1D1 until end of treatment. 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. 
 
- At the start of each infusion, participants may apply cooling eye masks for 
approximately 1 h or as long as tolerated. 
33. Antiviral prophylaxis (for example acyclovir or other according to institutional 
guidelines) is required for the duration of bortezomib treatment.   
34. EORTC QLQ-C30 AND QLQ-MY20 will be collected every 6 weeks, and 
PRO-CTCAE, OSDI and NEI-VFQ-25 will be collected every 3 weeks, even if 
cycle is delayed. Participants who cannot complete the self-administered 
version should use an Interviewer-Administered format. The interview may be 
administered over the telephone. If the Interviewer-Administered format is 
used, it should be read to the participants verbatim, and participant responses 
should be recorded directly without any interpretation.  Refer to SRM for 
further details. 


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Table 9 
Schedule of Activities - On Study Assessments for Arm B (belantamab mafodotin in combination with bortezomib 
plus dexamethasone) [21-day Cycle] - belantamab mafodotin STRETCH and S/D STRETCH Dosing Only 
Study Assessments1 
STRETCH Dosing Schedule 
Every 21 Days 
 
(Starting at 
Week 74 
regardless of 
dosing) 
Starting at 
Cycle 35 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes  
(Arm B belantamab mafodotin STRETCH and S/D STRETCH dosing 
only 
Cycle 1 
Cycle 2 
Day 
12 
D4, D8 
and D113 
Day 14 
D4, D8 and 
D113 
ECOG Performance 
Status 
 
 
 
 
X 
 
1. 
All assessments apply to Part 1 and 2 of the study, unless stated 
otherwise. 
2. 
Screening Assessments do not need to be repeated on C1D1 unless 
otherwise specified. 
3. 
D4, D8, and D11 are dosing days for bortezomib.  
4. 
All assessments starting at C1D1 and week 7 can be performed 
within 3 days prior to the scheduled date unless otherwise specified. 
5. 
Assessments scheduled on days of dosing should be done prior to 
drug administration, unless otherwise specified. Physical Exam must 
be within 72 h prior to 1st dose of study drugs to be administrated in 
that cycle. Body weight at C1D1 (prior to dosing) will be used for 
dose calculation of belantamab mafodotin.  Body weight to be 
measured prior to each dose. If the change of body weight is greater 
than 10%, the dose should be re-calculated based on the actual 
body weight at the time of dosing. Up to 8 cycles of bortezomib and 
dexamethasone in combination with belantamab mafodotin are 
allowed; after the 8th cycle of Bor/Dex, participants will be allowed to 
continue on belantamab mafodotin monotherapy until progressive 
disease, intolerable AEs, or death occurs. 
6. 
Treatment-related toxicities will be assessed for at least 70 days 
after the last dose regardless initiation of new anticancer therapy. All 
related SAEs are to be collected from consent through 
 follow-up. 
For reporting of ocular events see the guidance provided in 
Appendix 8. 
Adverse 
Events/SAEs6 
X 
X 
X 
X 
Ongoing 
Ongoing 
Concomitant 
Medications 
X 
X 
X 
X 
Ongoing 
Ongoing 
 
Safety 
Physical Exam 
X 
 
X 
 
X 
X5 
Ocular Exam7 
 
 
X 
 
X 
X 
Vital Signs (BP, Heart 
rate Body 
Temperature)8 
X 
X 
X 
X 
 
X 
(must also 
be done with 
each dose of 
bortezomib) 
Body Weight (BW) 
and Height 
BW 
only 
 
BW only 
 
 
BW only 
Hematology9 
X 
X 
X  
X  
X 
X  
(must also 
be done with 
each dose of 
bortezomib) 
Clinical chemistry9 
X 
X 
X 
X 
X 
X 
HbA1c 
As clinically indicated 
CC
I


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Study Assessments1 
STRETCH Dosing Schedule 
Every 21 Days 
 
(Starting at 
Week 74 
regardless of 
dosing) 
Starting at 
Cycle 35 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes  
(Arm B belantamab mafodotin STRETCH and S/D STRETCH dosing 
only 
Cycle 1 
Cycle 2 
Day 
12 
D4, D8 
and D113 
Day 14 
D4, D8 and 
D113 
C-reactive Protein 
(CRP)9 
 
 
 
 
X 
 
7. 
Participants will be assessed by a qualified eye care specialist 
(Appendix 12) on Day 1 (window of up to 5 days) of every 21-day 
cycle up to Dose 6 of belantamab mafodotin. All effort should be 
made to schedule the ophthalmologic exams prior to and as close to 
the belantamab mafodotin dosing as possible. If there are no 
significant ocular examinations findings, patient symptoms or vision 
changes at the time of the Dose 6 exam, participants may have their 
ophthalmologic exams decreased to once every 3 months. If a 
participant subsequently develops vision changes or other ocular 
symptoms, the participant should be promptly evaluated by a 
qualified eye care specialist. In case of persistent ophthalmic exam 
findings, newly developed ocular symptoms or vision changes at the 
Dose 6 exam, the participants will have further ophthalmologic 
exams, at least every 21-day cycle (regardless of dosing) until 
resolution (to Grade 1 or baseline) or more frequently as clinically 
indicated by the qualified eye care specialist. See Section 10.6.7.1 
for full details of ocular exam procedures. 
8. 
On each belantamab mafodotin dosing day, vital signs must be 
assessed within 30 min prior to Start of Infusion (SOI), within 15 min 
after End of Infusion (EOI), and at 1 h (15 min) after EOI. On days 
where vital sign time points align with PK sampling time points, vital 
signs should be assessed prior to belantamab mafodotin PK 
samples being drawn. Vital signs must be assessed within 30 mins 
before and within 15 min after each dose of bortezomib. 
9. 
Hematology and clinical chemistry must be repeated if not within 24 
h prior to 1st dose of study drugs to be administrated in that cycle. 
Hematology must be repeated prior to each dose of bortezomib. 
Urinalysis (dipstick)9 
X 
 
 
 
X 
 
Estimated Glomerular 
Filtration Rate (eGFR) 
by MDRD formula 
X 
 
 
 
X 
 
Spot urine for 
albumin/creatinine 
ratio10 
 
 
 
 
X 
 
Pregnancy Test for 
WOCBP11 
X 
 
X 
 
X 
X 
12-lead ECG12 
X 
 
X 
 
 
X 
ECHO – LVEF13 
 
 
 
 
Every 12 
weeks  
(At week 13, 
25, 37, 49 and 
so on) 
 
 
Disease Evaluation [every 3 weeks (3 days) even if the cycle is delayed]14 
SPEP (Serum Protein 
Electrophoresis) 
 
 
 
 
X 
 
Serum Kappa, lambda 
free LC, FLC ratio 
 
 
 
 
X 
 
Serum 
Immunofixation15 
 
 
 
 
At time of 
suspected CR 
then until 
suspected PD 
 


TMF-14624358 
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Study Assessments1 
STRETCH Dosing Schedule 
Every 21 Days 
 
(Starting at 
Week 74 
regardless of 
dosing) 
Starting at 
Cycle 35 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes  
(Arm B belantamab mafodotin STRETCH and S/D STRETCH dosing 
only 
Cycle 1 
Cycle 2 
Day 
12 
D4, D8 
and D113 
Day 14 
D4, D8 and 
D113 
UPEP (Urine Protein 
Electrophoresis) 
(on 24 h collected 
urine) 
 
 
 
 
X 
 
Starting at C9, hematology must be repeated prior to each dose of 
belantamab mafodotin. An additional hematology sample must be 
collected on D15 24 h for Cycles 1-8. On Day 1 of any planned 
cycle, Absolute Neutrophil Count (ANC) must be ≥1.0×109/L to 
administer treatment. Refer to Table 27 for comprehensive list of lab 
tests. 
10. Albumin/creatinine ratio (Spot urine from first void) every 3 weeks 3 
days (local lab, if local not available then central). 
11. Perform only in women of childbearing potential (WOCBP). A serum 
pregnancy test must be performed at screening; if the test is 
completed within 72 hours prior to the first dose of belantamab 
mafodotin, this assessment does not have to be repeated on C1D1. 
For questionable cases, follicle-stimulating hormone (FSH) and 
estradiol (as needed in WOCBP) should be performed at local lab to 
determine childbearing potential. WOCBP must have a negative 
highly sensitive serum pregnancy test within 72 hours of dosing on 
C1D1. Subsequent pregnancy test on dosing days may be either 
serum or urine test.  Each pregnancy test must be performed within 
24 h prior to dosing.  
12. SINGLE ECG performed pre-infusion on belantamab mafodotin 
dosing days. All ECGs will be collected centrally (refer to SRM for 
details). 
 
13. ECHO will be performed every 12 weeks (7 days) and locally.  
14. Disease evaluation (except imaging and skeletal survey) will 
continue to be performed, every 3 weeks (3 days) even if the cycle 
is delayed. 
Urine 
Immunofixation15 
 
 
 
 
At time of 
suspected CR 
then until 
suspected PD 
 
Ca corrected for 
Albumin (Serum) 
 
 
 
 
X 
 
IgG, IgM, IgA 
 
 
 
 
X 
 
IgD/IgE16 
 
 
 
 
X 
 
Imaging for 
extramedullary 
disease17 
 
 
 
 
Week 13, 25, 
37, 49 and then 
if clinically 
indicated 
 
Skeletal Survey18 
 
 
 
 
As clinically 
indicated 
 
Whole body PET/CT 
 
 
 
 
Only once at 
time of 
achieving CR 
or sCR 
(whichever 
comes first) 
according to 
IMWG 2016 
 
Response 
assessment by 
IMWG19 
 
 
 
 
X 
 


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73 
 
Study Assessments1 
STRETCH Dosing Schedule 
Every 21 Days 
 
(Starting at 
Week 74 
regardless of 
dosing) 
Starting at 
Cycle 35 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes  
(Arm B belantamab mafodotin STRETCH and S/D STRETCH dosing 
only 
Cycle 1 
Cycle 2 
Day 
12 
D4, D8 
and D113 
Day 14 
D4, D8 and 
D113 
 
15. At time of first achieving SPEP or Urine M protein ~0 g/dl (suspected 
CR) and until suspected PD after CR or stringent Complete 
Response (sCR). 
16. Only in participants with IgD/IgE myeloma  
17. Imaging is only required for participants with extramedullary disease 
at week 13, 25, 37, 49 (±7 days) and then if clinically indicated by 
either CT, MRI, or PET/CT per local guidance. Needs to be 
performed by the same method throughout the study as was done at 
baseline (i.e., if CT/PET scan was used as baseline, participant 
needs to be followed by CT/PET scans).  Selected target lesion 
needs to be measured and followed over time. Plasmacytoma 
measurements should be taken from the CT portion of the PET/CT, 
or MRI scans, or dedicated CT scans where applicable. 
For participants with only skin involvement, skin lesions should be 
measured with a ruler.  Measurement of tumor size will be 
determined by the Sum of the Products of the maximal perpendicular 
diameters of measured lesions (SPD).  
18. Imaging of bones for lytic lesions by method aligned with institutional 
guidance (X-ray, CT or MRI). Survey results within 30 days prior to 
C1D1 date are acceptable. At later cycles, repeat as clinically 
indicated, or if worsening clinical symptoms suggest PD, by the 
same method used as at screening. 
19. Response to treatment will be assessed every 3 weeks (3 days), 
based on laboratory tests and imaging (if applicable), using IMWG 
criteria.   
20. Whenever CR is assessed, if possible, a further BM aspirate sample 
may be taken at the same time for biomarker analysis. 
Bone Marrow Tests 
BM aspirate/biopsy for 
Disease 
Assessment20,24 
 
 
 
 
At time of 
suspected CR 
or at time of 
suspected PD 
(only if PD not 
evident 
otherwise) 
 
BM biopsy to confirm 
sCR by IHC 
 
 
 
 
Upon achieving 
CR 
 
BM aspirate for 
 
 testing21   
 
 
 
 
At time of first 
achieving 
VGPR or better 
 
 
Biomarkers 
X 
 
X 
 
 
X 
X 
 
 
 
At time of 
achieving 
VGPR or 
better21 
 
 
Optional  
Optional tissue 
sample at PD for 
BCMA expression and 
biomarker research24 
 
 
 
 
X 
 
CCI
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Study Assessments1 
STRETCH Dosing Schedule 
Every 21 Days 
 
(Starting at 
Week 74 
regardless of 
dosing) 
Starting at 
Cycle 35 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes  
(Arm B belantamab mafodotin STRETCH and S/D STRETCH dosing 
only 
Cycle 1 
Cycle 2 
Day 
12 
D4, D8 
and D113 
Day 14 
D4, D8 and 
D113 
Genetic sample25 
X 
 
 
 
 
 
21. 
 to be performed by the central lab at 
the time of first achieving VGPR or better. Thereafter, 
 
should be repeated every 6 months until PD or CR. In case of 
deepening of response from VGPR to CR, or achieving CR without 
prior VGPR, 
 should be performed at the time of 
achieving suspected CR and repeated every 6 months until PD. 
Whenever possible, a further BM aspirate sample may be taken at 
the same time for biomarker analysis. Additionally, collect blood 
plasma for 
 analysis. 
24. The optional PD tissue sample should contain tumor cells, either BM 
aspirate clot, or other tissue in case of extramedullary disease. 
Samples will be submitted to central lab for BCMA analysis, any 
remaining bone marrow and/or tissue sample will be used for 
biomarker research. 
25. Informed consent for optional sub-studies (e.g. genetic research) 
must be obtained before collecting a sample. The sample will be 
collected at the first opportunity after a participant has met all 
eligibility requirements, before/ on C1D1 prior to infusion. If 
insufficient DNA was extracted, or the sample was damaged or 
otherwise could not be processed, the site may be requested to 
recollect the genetic sample where applicable. 
26. PK samples to be taken in all participants for belantamab mafodotin 
measurement on: 
 
PK and ADA 
Pharmacokinetic 
blood sampling for 
belantamab 
mafodotin22,26 
X26 
 
X26 
 
 
X (at 
selected 
cycles)26 
 
 
 
 
 
 
 
Anti-drug antibodies 
(ADA)27 
X27 
 
 
 
 
X (at 
selected 
cycles)27 
 
Treatment 
Premedication if 
needed28 
X 
 
 
 
 
X 
Administration of 
belantamab 
mafodotin29 
2.5 
mg/kg 
on 
C1D1 
 
 
 
 
2.5 mg/ kg 
STRETCH: 
2.5 mg/kg on 
Day 1: at 
least 42 (3) 
days 
between 
consecutive 
doses of 
belantamab 
mafodotin.  
CCI
CCI
CCI
CCI
CCI


TMF-14624358 
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75 
 
Study Assessments1 
STRETCH Dosing Schedule 
Every 21 Days 
 
(Starting at 
Week 74 
regardless of 
dosing) 
Starting at 
Cycle 35 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes  
(Arm B belantamab mafodotin STRETCH and S/D STRETCH dosing 
only 
Cycle 1 
Cycle 2 
Day 
12 
D4, D8 
and D113 
Day 14 
D4, D8 and 
D113 
S/D 
STRETCH: 
1.9 mg/kg on 
Day 1: at 
least 42 (3) 
days 
between 
consecutive 
doses of 
belantamab 
mafodotin. 
Belantamab mafodotin Dose 1 (Cycle 1)  
• 
Day 1: at pre-infusion (within 30 min prior to SOI), End of 
Infusion (0 to 15 min after EOI), at 2 h (± 15 min) after SOI 
and 24h (±2 h) after SOI.  
• 
Day 4: one PK sample to be taken prior to Bor/Dex 
administration 
• 
Day 11: one PK sample to be taken prior to Bor/Dex 
administration 
• 
Day 22 (C2D1): one PK sample to be taken prior to Bor/Dex 
administration 
Belantamab mafodotin Dose 2  
• 
Day 1: at pre-infusion (within 30 min prior to SOI) and EOI (0 
to 15 min after EOI).  
• 
If Dose 2 is delayed, collect one PK sample on this day (Dose 
1 Day 43) regardless of dosing. 
• 
Day 4: one PK sample to be taken prior to Bor/Dex 
administration 
• 
Day 11: one PK sample to be taken prior to Bor/Dex 
administration 
Belantamab mafodotin Dose 3  
• 
Day 1: at pre-infusion (within 30 min prior to SOI) and EOI (0 
to 15 min after EOI). 
• 
Day 22: one PK sample to be taken prior to Bor/Dex  
Belantamab mafodotin Dose 4 
• 
Day 1: at pre-infusion (within 30 min prior to SOI) and EOI (0 
to 15 min after EOI).  
Belantamab mafodotin Dose 5  
• 
Day 1: at pre-infusion (within 30 min prior to SOI). 
1.9 
mg/kg 
on 
C1D1 
 
 
 
 
1.9 mg/ kg 
STRETCH: 
1.9 mg/kg on 
Day 1: at 
least 42 (3) 
days 
between 
consecutive 
doses of 
belantamab 
mafodotin. 
Administration of 
bortezomib30 
X 
1.3 mg/m2 
SC or IV 
on Days 
1, 4, 8 
and 11 of 
each 21-
day cycle 
X 
1.3 mg/m2 SC 
or IV on Days 
1, 4, 8 and 11 
of each 21-
day cycle 
 
1.3 mg/m2 
SC or IV on 
Days 1, 4, 8 
and 11 of 
each 21-day 
cycle 


TMF-14624358 
CONFIDENTIAL 
 
 
207497 
 
Protocol Amd 04 
 
76 
 
Study Assessments1 
STRETCH Dosing Schedule 
Every 21 Days 
 
(Starting at 
Week 74 
regardless of 
dosing) 
Starting at 
Cycle 35 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes  
(Arm B belantamab mafodotin STRETCH and S/D STRETCH dosing 
only 
Cycle 1 
Cycle 2 
Day 
12 
D4, D8 
and D113 
Day 14 
D4, D8 and 
D113 
Administration of 
dexamethasone31 
X 
20 mg PO 
or IV on 
Days 1, 2, 
4, 5, 8, 9, 
11, and 
12 of 
each 21-
day cycle 
X 
20 mg PO or 
IV on Days 1, 
2, 4, 5, 8, 9, 
11, and 12 of 
each 21-day 
cycle 
 
20 mg PO or 
IV on Days 
1, 2, 4, 5, 8, 
9, 11, and 12 
of each 21-
day cycle 
Belantamab mafodotin Dose 6  
• 
Day 1: at pre-infusion (within 30 min prior to SOI) and EOI (0 
to 15 min after EOI) 
• 
Day 22: one PK sample to be taken prior to Bor/Dex  
Belantamab mafodotin Dose 9: 
• 
Day 1: at pre-infusion (within 30 min prior to SOI) 
For treatment beyond Dose 9 of belantamab mafodotin, pre-infusion 
samples will be collected every 3rd Dose of belantamab mafodotin 
(Dose 12, Dose 15, Dose 18 and so on, until PD). 
 samples 
will be collected every time a belantamab mafodotin PK sample is 
collected. See footnote 22.   
27. All ADA samples will be collected prior to each belantamab 
mafodotin infusion (at Dose 1 (C1) D1, Dose 2, 3, 6, 9 and 12) both 
in Part 1 and Part 2 (at the same time as the pre-infusion 
belantamab mafodotin PK samples are taken); for treatment beyond 
12 cycles, collect samples for ADA analysis prior to each infusion 
every 6th Dose of belantamab mafodotin (Dose 18, Dose 24, Dose 
30 and so on, until PD). 
28. Premedication should be considered in any participant who 
experienced an IRR during the first or any subsequent infusion with 
belantamab mafodotin. 
29. Belantamab mafodotin will be administered first as a 30 min to 1 h 
infusion, followed by 1-2 h rest period. A window of 3 days is 
acceptable for administration of study treatment after C1. Please 
refer to Section 8.2 for dose modification guidance.  Note: STRETCH 
Dosing Schedule: belantamab mafodotin will be administered as a 
full dose on D1 of every alternate 21-day cycle. For example: A 2.5 
mg/kg STRETCH will administer a 2.5 mg/kg dose on Day 1 of every 
alternate 21-day cycles i.e. STRETCH (C1, C3, C5, C7 and so on). A 
Preservative-free 
artificial tears32 
X 
Cooling eye masks32 
X 
 
X 
 
 
X 
Antiviral prophylaxis33 
X 
 
Health Outcomes 
EORTC QLQ-C30 
AND QLQ-MY20 (Part 
1 and Part 2)34 
X 
 
 
 
Every 6 weeks 
starting at W7 
 
PRO-CTCAE34 
X 
 
 
 
X 
 
OSDI and NEI-VFQ-
2534 
X 
 
 
 
X 
 
 
CCI


TMF-14624358 
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77 
 
Study Assessments1 
STRETCH Dosing Schedule 
Every 21 Days 
 
(Starting at 
Week 74 
regardless of 
dosing) 
Starting at 
Cycle 35 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes  
(Arm B belantamab mafodotin STRETCH and S/D STRETCH dosing 
only 
Cycle 1 
Cycle 2 
Day 
12 
D4, D8 
and D113 
Day 14 
D4, D8 and 
D113 
S/D STRETCH will administer a 2.5 mg/kg dose on C1 D1 and for 
subsequent cycles a 1.9 mg/kg dose will be administered on Day 1 
of all alternate 21-day cycles C3 onwards (C3, C5, C7 and so on).   
1.9 mg/kg STRETCH will administer a 1.9 mg/kg dose administered 
on Day 1 of every alternate 21-day cycles i.e. STRETCH (C1, C3, 
C5, C7 and so on). 
30. Bortezomib 1.3 mg/m2 SC or IV (depending on participants’ and 
institutional preference) on Days 1, 4, 8, and 11 of every 21-day 
cycle for a total up to 8 cycles. Please refer to Section 8.2 for dose 
modification guidance. 
         Note: Participants will receive antiviral prophylaxis (for example 
acyclovir or other according to the institutional guidelines), for the 
entire duration of treatment with Bor/Dex (8 cycles). 
31. Dexamethasone 20 mg PO or IV will be given on Days 1, 2, 4, 5, 8, 
9, 11, and 12 of every 21-day cycle. Dexamethasone will be given 
for a total of up to 8 cycles.  If dexamethasone is taken at home, it 
should be taken approximately at the same time each day. 
Participant Diary will be used to keep record of self-administer oral 
dexamethasone at home. Participants who are >75y with BMI <18.5 
kg/m2, the dose of dexamethasone can be reduced to 10 mg. If 
intolerance to dexamethasone develops, dexamethasone may be 
reduced to 10 mg. If 10 mg is not tolerated, the dexamethasone 
dose can be further reduced or permanently discontinued. Please 
refer to Section 8.2 for dose modification guidance. 
32. Corneal Events Management:  
        - Prophylactic preservative-free artificial tears must be administered 
in each eye at least 4-8 times daily beginning on C1D1 until end of 
treatment. 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. 


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STRETCH Dosing Schedule 
Every 21 Days 
 
(Starting at 
Week 74 
regardless of 
dosing) 
Starting at 
Cycle 35 
 
(Prior to the 
first dose of 
any study 
drugs at the 
given cycle) 
Notes  
(Arm B belantamab mafodotin STRETCH and S/D STRETCH dosing 
only 
Cycle 1 
Cycle 2 
Day 
12 
D4, D8 
and D113 
Day 14 
D4, D8 and 
D113 
 
- At the start of each infusion, participants may apply cooling eye 
masks to for approximately 1 h or as long as tolerated. 
33. Antiviral prophylaxis (for example acyclovir or other according to 
institutional guidelines) is required for the duration of bortezomib 
treatment.   
34. EORTC QLQ-C30 AND QLQ-MY20 will be collected every 6 weeks, 
and PRO-CTCAE, OSDI and NEI-VFQ-25 will be collected every 3 
weeks, even if cycle is delayed. Participants who cannot complete 
the self-administered version should use an Interviewer-
Administered format. The interview may be administered over the 
telephone. If the Interviewer-Administered format is used, it should 
be read to the participants verbatim, and participant responses 
should be recorded directly without any interpretation.  Refer to SRM 
for further details. 
 
Table 10 
Schedule of Activities – End of Treatment & Follow-Up Assessments Both for Arm A (belantamab mafodotin in 
combination with lenalidomide plus dexamethasone) and Arm B (belantamab mafodotin in combination with 
bortezomib plus dexamethasone) 
Study Assessments1 
End of 
Treatment 
Visit2 
 Follow-up 
Visit3 
 
Follow-
up Visit4 
Notes (Arm A and Arm B End of Treatment and Follow-up) 
ECOG Performance Status 
X 
X 
 
1. All assessments apply to Part 1 and 2 unless stated otherwise. All assessments 
can be performed within 3 days prior to the scheduled date unless otherwise 
specified.   
Adverse Events/ SAEs 5 
X 
X 
 
Concomitant Medications 
X 
X 
 
 
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End of 
Treatment 
Visit2 
 Follow-up 
Visit3 
 
Follow-
up Visit4 
Notes (Arm A and Arm B End of Treatment and Follow-up) 
Safety 
2. End of Treatment (EOT) visit will occur within 45 days from the last dose of any 
study medication, or prior to initiation of new anti-cancer therapy (whichever occurs 
first). AEs and SAEs will be collected up to at least 70 days after the last dose, 
either via phone or a follow up visit.  
3. The
) Follow-up Visit, (for participants who 
discontinue study treatment for a reason other than PD) should be conducted every 
4 weeks (3 days) for Arm A and every 3 weeks (3 days) for Arm B until 
confirmed PD, death, start of a new anticancer treatment, withdrawal of consent, or 
end of the study whichever occurs first. 
4. The 
 Follow-up Visit will be performed in all participants who 
come off treatment completely.  Participants will be followed for survival and 
subsequent anticancer therapy by chart review, phone call, or any form of 
communication every 3 months (±7 days) until study ends.  Record the participant’s 
survival status and whether subsequent treatment for disease was given. 
Participant does not need to come in for visit. 
5. Treatment-related toxicities will be assessed for at least 70 days after the last dose 
of treatment regardless initiation of new anticancer therapy. All related SAEs are to 
be collected from consent through 
 follow-up. For reporting of ocular events see 
the guidance provided in Appendix 8. 
6. End of Treatment visit ophthalmic exam to be performed by a qualified eye care 
specialist. Participants with corneal signs per the GSK scale at the End of 
Treatment Visit will be followed once every 3 months (7 days) by a qualified eye 
care specialist until resolution to their baseline, starting another anti-cancer 
therapy, or up to 1 year (whichever comes first). See Section 10.6.7.1 for list of 
ophthalmic exam procedures and Appendix 12 for qualifications and requirements 
of the eye care specialist. 
7. Refer to Table 27 for comprehensive list of lab tests.  
8. Final pregnancy test (serum or urine) must be performed in women of child-bearing 
potential at the EOT Visit, the 
Follow-up Visit, and (1) Arm A: 4 months after 
the last dose of belantamab mafodotin or 4 weeks after the last dose of 
lenalidomide, whichever is longer; or (2) Arm B: 4 months after the last dose of 
belantamab mafodotin or 7 months after the last dose of bortezomib whichever is 
longer (may be via a urine pregnancy test kit mailed to the participant’s home with 
results reported by telephone). 
Physical Exam 
X 
X 
 
Ocular Exam6 
X 
X 
X 
Vital Signs (BP, Heart rate Body 
Temperature) 
X 
X 
 
Body Weight (BW) and Height 
BW only 
BW only 
 
Hematology7 
X 
X 
 
Clinical chemistry7 
X 
X 
 
HbA1c 
As clinically 
indicated 
 
 
C-reactive Protein (CRP)7 
X 
 
 
Urinalysis (dipstick) 7 
X 
X 
 
Estimated Glomerular Filtration Rate 
(eGFR) by MDRD formula 
X 
 
 
Pregnancy Test for WOCBP8 
X 
X 
X 
12-lead ECG9 
X 
 
 
ECHO – LVEF10 
X 
 
 
 
Disease Evaluation11 
SPEP (Serum Protein Electrophoresis) 
X 
X 
 
Serum Kappa, lambda free LC, FLC 
ratio 
X 
X 
 
Serum Immunofixation12 
At time of 
suspected CR 
until 
suspected PD 
At time of 
suspected CR 
until suspected 
PD 
 
UPEP (Urine Protein Electrophoresis) 
(on 24 h collected urine) 
X 
X 
 
Urine Immunofixation12 
At time of 
suspected 
CR, then until 
suspected PD 
At time of 
suspected CR, 
then until 
suspected PD 
 
Ca corrected for Albumin (Serum) 
X 
X 
 
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End of 
Treatment 
Visit2 
 Follow-up 
Visit3 
 
Follow-
up Visit4 
Notes (Arm A and Arm B End of Treatment and Follow-up) 
IgG, IgM, IgA 
X 
X 
 
9. One SINGLE ECG at End of Treatment Visit.  
10. ECHO to be performed locally. 
11. Disease evaluation (except imaging) will continue to be performed, every 4 weeks 
(3 days) for Arm A and every 3 weeks (3 days) for Arm B, until confirmed PD, 
death, start of a new anticancer treatment, withdrawal of consent, or end of the 
study whichever occurs first. 
12. At time of first achieving SPEP or Urine M protein ~0 g/dl (suspected CR) and until 
suspected PD after CR or sCR. 
13. Only in participants with IgD/IgE myeloma. 
14. Imaging is only required for participants with known extramedullary disease by 
either CT, MRI, or PET/CT per local guidance. Needs to be performed by the same 
method throughout the study as was done at baseline (i.e., if CT/PET scan was 
used as baseline, participant needs to be followed by CT/PET scans).  Selected 
target lesion needs to be measured and followed over time. Plasmacytoma 
measurements should be taken from the CT portion of the PET/CT, or MRI scans, 
or dedicated CT scans where applicable. A window of  7days is acceptable for 
imaging. 
For participants with only skin 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). 
15. Imaging of bones for lytic lesions by method aligned with institutional guidance (X-
ray, CT or MRI). As clinically indicated, or if worsening clinical symptoms suggest 
PD, by the same method used as at screening. 
16. Response to treatment will be assessed, based on laboratory tests and imaging (if 
applicable), using IMWG criteria [Kumar, 2016]. 
17. Whenever CR is assessed, if possible, a further BM aspirate sample may be taken 
at the same time for biomarker analysis. 
18.
 is not to be done at each 
 visit.  
) 
to be performed by the central lab if the participant enters 
 with a VGPR or 
better. Thereafter, 
 should be repeated every 6 months until PD, death, 
start of a new anticancer treatment, withdrawal of consent, or end of the study 
whichever occurs first. The 6-month window is intended to be a continuation of the 
interval whenever the 
 was last performed prior to participant moving 
IgD/IgE13 
X 
X 
 
Imaging for extramedullary disease14 
As clinically 
indicated 
As clinically 
indicated 
 
Skeletal Survey15 
As clinically 
indicated 
As clinically 
indicated 
 
Response assessment by IMWG16 
X 
X 
 
 
Bone Marrow Tests 
BM aspirate/biopsy for Disease 
Assessment17,19 
At time of 
suspected CR 
or at time of 
suspected PD 
(only if PD not 
evident 
otherwise) 
At time of 
suspected CR or 
at time of 
suspected PD 
(only if PD not 
evident 
otherwise) 
 
BM biopsy to confirm sCR by IHC 
Only if CR has 
been achieved 
by this visit 
Only if CR has 
been achieved 
by this visit 
 
BM aspirate for 
 
 testing 
 
X18  
 
 
X 
 
 
X 
 
 
 
Optional 
Optional tissue sample at PD for BCMA 
expression and biomarker research19 
Optional at PD 
Optional at PD 
 
 
PK and ADA 
Pharmacokinetic blood sampling for 
belantamab mafodotin20 
X 
 
 
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Study Assessments1 
End of 
Treatment 
Visit2 
Follow-up 
Visit3 
 
Follow-
up Visit4 
Notes (Arm A and Arm B End of Treatment and Follow-up) 
Anti-drug antibodies (ADA)21 
X 
 
 
into 
follow-up. Whenever possible, a further BM aspirate sample may be taken 
at the same time for biomarker analysis. Additionally, collect blood plasma for 
analysis.  
19. The optional PD tissue sample should contain tumor cells, either BM aspirate clot, 
or other tissue in case of extramedullary disease. Samples will be submitted to 
central lab for BCMA analysis, any remaining bone marrow and/or tissue sample 
will be used for biomarker research. 
20. A pharmacokinetic sample will be collected from each participant at the EOT Visit. 
It should be accompanied by a
 sample. 
21. A final ADA sample will also be drawn at the End of Treatment Visit. 
22. EORTC QLQ-C30, QLQ-MY20, PRO-CTCAE, OSDI and NEI-VFQ-25 will be 
collected at the EOT Visit. Participants who still show corneal signs per the GSK 
scale at EOT will continue to receive the OSDI and NEI-VFQ-25 assessments 
during follow-up visit or via telephone for up to 1 year or until ocular exams are 
completed (whichever comes first). For all measures, participants who cannot 
complete the self-administered version should use an Interviewer-Administered 
format. The interview may be administered over the telephone. If the Interviewer-
Administered format is used, it should be read to the participants verbatim, and 
participant responses should be recorded directly without any interpretation.  Refer 
to SRM for further details. 
 
Health Outcomes 
EORTC QLQ-C30 AND QLQ-MY20 
(Part 1 and Part 2)22 
X 
 
 
PRO-CTCAE22 
X 
 
 
OSDI and NEI-VFQ-2522 
X 
X 
X 
 
Others 
Survival Status phone call 
 
 
X 
Subsequent anti-MM Treatment 
 
X 
X 
 
Abbreviations:   
ADA = Anti-drug Antibody; BM= Bone marrow; BCMA= B-cell maturation antigen; BCVA = best-corrected visual acuity; BW = body weight; C1D1 = Cycle 1 Day 1, etc.;
 
; CRP = C-reactive protein; ECHO = Echocardiogram; EM = extramedullary; EOI = End of Infusion; EORTC QLQ-C30  = European Organisation for Research and 
Treatment of Cancer Quality of Life Questionnaire 30-item Core module; EORTC QLQ-MY20 = European Organisation for Research and Treatment of Cancer Quality of Life 
Questionnaire 20-item Multiple Myeloma module; FISH= Fluorescence-in-situ hybridization; FLC = free light chain; IHC = immunohistochemistry; IMWG = International Myeloma 
Working Group; LVEF = Left ventricular ejection fraction; 
; NEI-VFQ-25 = National Eye Institute 25-item Visual Function Questionnaire; OSDI = Ocular 
Surface Disease Index; PD = progressive disease; PET/CT = Positron emission tomography/computed tomography; PK = Pharmacokinetics; PO = orally; PRO-CTCAE = Patient-
Reported Outcomes Version of the Common Term Criteria for Adverse Events; QD = once/day (on specified days); SAEs = Serious adverse events; SOI = start of infusion; SPEP = 
serum protein electrophoresis; UPEP = urine protein electrophoresis; VGPR = Very good partial response; WOCBP = women of child-bearing potential. 
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4. 
INTRODUCTION 
4.1. 
Study Rationale 
The incorporation of proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) 
into the standard of care (SoC) treatment has improved outcomes in patients with 
multiple myeloma over the past 10 years [Kumar, 2014; Kumar, 2008; Richardson, 
2007], but most patients still eventually relapse and will require subsequent treatments 
[Moreau, 2015].  
Bortezomib and lenalidomide are used in combination with dexamethasone to treat the 
relapsed disease. The recent addition of monoclonal antibodies (elotuzumab and 
daratumumab) to the treatment paradigm has demonstrated that the results achieved can 
be improved significantly. Elotuzumab, an immunostimulatory monoclonal antibody (that 
targets signaling lymphocytic activation molecule F7, or SLAMF7) has no anti-myeloma 
activity on its own, but when combined with lenalidomide-dexamethasone (Len/Dex) 
superior activity to Len/Dex alone was shown in a Phase 3 study (Eloquent-2 study) 
[Lonial, 2015]. The median Progression-free Survival (PFS) in the elotuzumab group was 
19.4 months, versus 14.9 months in the control group; yielding a hazard ratio (HR) for 
progression or death in the elotuzumab group of 0.70 (95% CI: 0.57 to 0.85; p<0.001). 
The Overall Response Rate (ORR) in the elotuzumab group was 79%, versus 66% in the 
control group (p<0.001).  
Similarly, the addition of daratumumab to lenalidomide and dexamethasone significantly 
lengthened PFS among patients with relapsed or refractory multiple myeloma (RRMM) 
[Dimopoulos, 2016].  A median follow-up of 13.5 months, and 169 events of disease 
progression or death were observed (in 53 of 286 patients [18.5%] in the daratumumab 
group vs. 116 of 283 [41.0%] in the control group; hazard ratio, 0.37; 95% CI: 0.27 to 
0.52; p<0.001 by stratified log-rank test). The Kaplan-Meier rate of PFS at 12 months 
was 83.2% (95% CI: 78.3 to 87.2) in the daratumumab group, compared to 60.1% (95% 
CI: 54.0 to 65.7) in the control group. A significantly higher rate of overall response was 
observed in the daratumumab group than in the control group (92.9% vs. 76.4%, 
p<0.001). Daratumumab was associated with infusion-related reactions and a higher rate 
of neutropenia than the control therapy. 
Daratumumab in combination with bortezomib and dexamethasone also resulted in 
significantly longer PFS than bortezomib and dexamethasone alone [Dimopoulos, 2016]. 
The 12-month PFS rate was 60.7% in the daratumumab group versus 26.9% in the 
control group. After a median follow-up period of 7.4 months, the median PFS was not 
reached in the daratumumab group, but was 7.2 months in the control group, with the HR 
for progression or death with daratumumab vs. control, 0.39 (95% CI: 0.28 to 0.53; 
p<0.001). The rate of overall response was higher in the daratumumab group than in the 
control group (82.9% vs. 63.2%, p<0.001). Treatment with daratumumab combined with 
bortezomib plus dexamethasone was associated with infusion-related reactions and 
higher rates of thrombocytopenia and neutropenia than bortezomib plus dexamethasone 
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Belantamab mafodotin is an antibody drug conjugate targeting B cell maturation antigen 
(BCMA), which has demonstrated single-agent activity in the first-time-in-human trial 
(BMA117159) [Trudel, 2018; Trudel, 2019]. The ORR was 60% (95% CI: 42.1, 76.1) 
and the median PFS was 12 months in a heavily pretreated RRMM population (57% of 
patients had 5 or more prior lines of therapy). In the Phase 2 study 205678, at 2.5 mg/kg 
the ORR was 32% (97.5%CI: 21.7,43.6) and the median duration of response was 11.0 
months (95%CI: 4.2,NR).   
Given the previous experience with monoclonal antibodies, which exhibited lower single 
agent activity as monotherapy in similar populations, the combination therapy of 
belantamab mafodotin with SoC agents is an attractive option to explore for patients with 
RRMM who have been pre-treated with at least one prior line.  The combination with 
SoC therapies (Len/Dex, or Bor/Dex) is expected to result in additive, or enhanced 
effects which could potentially translate into a deep and long lasting response over what 
has been achieved with other available agents.  This study will evaluate the safety and 
tolerability profile of different doses and dosing schedule for belantamab mafodotin when 
administered in combination with approved regimens of either Len/Dex (Arm A) or 
Bor/Dex (Arm B).  Part 2 of the study will evaluate the preliminary clinical activity at the 
multiple dose levels and schedules for belantamab mafodotin in combination with 
Len/Dex (Arm A) or Bor/Dex (Arm B) in additional participants with RRMM. 
4.2. 
Background 
4.2.1. 
Current Treatment of Multiple Myeloma 
Multiple myeloma (MM) is an incurable malignancy and accounts for 1% of all cancers 
and for 10% of all hematologic malignancies. Worldwide, approximately 103,000 new 
cases are diagnosed annually, and an estimated 30,330 new cases and 12,650 deaths will 
occur in the U.S. in 2016 [Siegel, 2016]. Despite significant advances, current novel 
therapies and hematopoietic stem cell transplant (HSCT) cannot achieve cure, and most 
MM patients will die of relapse. Thus, new treatments are urgently needed.  
A variety of drugs and combination treatments have been evaluated and found effective 
in treating multiple myeloma [Moreau, 2017; National Comprehensive Cancer Network, 
2016]; however, most, if not all patients treated with these combinations inevitably 
relapse [Hanley, 2017; Jagannath, 2008; Richardson, 2003; Richardson, 2006]. Each 
relapse requires salvage therapy, and the duration of response (DoR) to each subsequent 
line of salvage therapy typically decreases. For example, in a retrospective chart review 
of patients who become refractory to bortezomib and IMIDs, the median overall survival 
(OS) time was disappointingly short (~ 9 months), with 7% achieving VGPR, 24% 
achieving partial response (PR), and 10% with stable disease after retreatment [Kumar, 
2012]. While the main treatment goal for RRMM is usually the preservation of organ 
function, control of the disease, and maintaining quality of life, the depth of response is 
also considered a predictor of durability of response and patient survival [Lonial, 2014]. 
There is an urgent need to develop treatment combinations with mechanisms of action 
that do not overlap with the current SoC treatments, and where cross-resistance with prior 
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monoclonal antibodies (mAb) such as daratumumab (targeting CD38) or elotuzumab 
(targeting signaling lymphocyte activation molecule [SLAMF7]) in combination with 
standard of care drugs [Lokhorst, 2015; Lonial, 2014; National Comprehensive Cancer 
Network, 2016]. 
The immunomodulatory agents (IMIDs) and PIs which are often administered in 
combination with dexamethasone are considered corner stone treatments for MM, and are 
therefore good candidates for combinations where additional improvements in efficacy 
could be achieved when combined with belantamab mafodotin.  
4.2.2. 
Role of B-Cell Maturation Antigen in Multiple Myeloma 
B-cell maturation antigen (BCMA), also designated as tumor necrosis factor receptor 
superfamily member 17 (TNFRSF17), is expressed on the surface of normal and 
malignant B lymphocytes at later stages of differentiation as they mature [Novak, 2004]. 
Ligands targeting BCMA such as B-cell activating factor (BAFF, TNFSF13B), along 
with a proliferation-inducing ligand (APRIL, TNFSF13) activate cell proliferation 
pathways and upregulate anti-apoptotic proteins in MM cell lines [Bellucci, 2005; 
Moreaux, 2004; Thompson, 2000]. 
) is present in the serum of 
MM patients [Laurent, 2015], and its levels have been postulated to correlate with 
response to therapy and OS [Sanchez, 2012]. Mice deficient for BCMA are viable, have 
normal B-cell development, and exhibit normal humoral responses [Belnoue, 2008; 
Jiang, 2011; Varfolomeev, 2004].  BCMA is widely expressed on malignant plasma cells 
in MM and to a lesser degree in other B-cell malignancies [Tai, 2015; Tai, 2006]. The 
restricted expression profile of BCMA makes it a very good target for a therapeutic 
antibody with direct cell killing activity and expected to have limited off target effects 
[Tai, 2015].  
BCMA has been validated as a therapeutic target in MM in preclinical studies [Tai, 
2015], and with belantamab mafodotin as single agent. Single-agent activity of 
belantamab mafodotin in heavily pre-treated RRMM patients has been shown in clinical 
trials [Trudel, 2019; Lonial, 2020].  
4.2.3. 
Antibody-Drug Conjugate Belantamab Mafodotin  
Belantamab mafodotin binds to BCMA and kills MM cells via a multi-modal mechanism 
including delivery of cytotoxic, MMAF (cysteine maleimidocaproyl MMAF 
[cys-mcMMAF]) to BCMA-expressing MM cells, thereby inducing apoptosis, enhancing 
antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis, 
and inducing immunogenic cell death (Figure 3) [Tai, 2014; Montes De Oca, 2019]. 
Exposure of dendritic cells to tumor cells undergoing immunogenic cell death is expected 
to result in an antigen-specific T-cell response, enhancing the immunogenic response 
against MM. 
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Figure 3 
Belantamab Mafodotin Mechanism of Action 
 
ADCC/ADCP=antibody-dependent cell-mediated cytotoxicity/antibody-dependent cellular phagocytosis 
4.2.4. 
Clinical Experience with Belantamab Mafodotin 
Single-agent belantamab mafodotin has demonstrated to have a strong single-agent 
activity with a well-defined manageable safety profile in heavily pre-treated participants 
with RRMM (Q3W schedule via IV administration).   Safety data for single-agent 
belantamab mafodotin were pooled (data as of 20Sep2019) 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. 
4.2.4.1. 
Clinical activity in studies with belantamab mafodotin monotherapy 
FTIH study BMA117159/DREAMM-1 
In the FTIH DREAMM-1 study, which consisted of a dose escalation phase (Part 1, 
n=38) and a dose expansion phase (Part 2, n=35), as of the primary analysis cut-off date 
of 31 August 2018, a total of 73 participants with RRMM received at least 1 dose of 
belantamab mafodotin [GSK Document Number 2013N175128 V08, 2020; Trudel, 
2019]. Estimated  target engagement, as indicated by
 binding >90%, was seen at 
doses of 1.92 mg/kg and higher. 
As of the efficacy cut-off date of 31 August 2018, a total of 35 participants were treated 
at the 3.4 mg/kg dose in Part 2 of the DREAMM-1 study. Participants were heavily pre-
treated: 57% of participants had 5 or more prior lines of therapy. The ORR was 60% 
(95% CI: 42.1, 76.1): comprised of PR, 6%; VGPR, 40%; CR, 9%; and stringent CR 
(sCR), 6%. The median duration of response (DoR) was 14.3 months (95% CI: 10.6, 
NR). The median PFS (mPFS) in this population was 12.0 months (95% CI: 3.1, not 
estimable [NE]). For participants refractory to both IMiDs and PIs (n = 32/35), the 
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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 IMiD and a proteasome inhibitor.  A total of 194 
participants received frozen drug product in the main cohort and 24 participants received 
3.4 mg/kg lyophilized drug product.  Primary analysis data from this study indicated no 
new safety signals, and the profile of adverse events was similar to the experience in the 
DREAMM-1 study for both arms. Both dose levels, 2.5 and 3.4 mg/kg, were shown to 
have a positive benefit/risk profile [Li, 2017; Lonial, 2020].  
As of the cut-off date of 31 January 2020, the study met its primary endpoint for ORR in 
both the 2.5 mg/kg [ORR 31% (97.5% CI 21.7,43.6)] and 3.4 mg/kg [ORR 35% (97.5% 
CI 24.8,47.0)] frozen treatments, and the benefit of belantamab mafodotin was supported 
by the secondary endpoints.  The median DoR was 11.0 months (95% CI: 4.2, NR) at 2.5 
mg/kg and 6.2 months (95% CI: 4.8, NR) at 3.4 mg/kg. The mPFS in this population was 
2.8 months (95% CI: 1.6, 3.6) and 3.9 months (95% CI: 2.0, 5.8), respectively and the 
median Overall Survival (mOS) was 13.7 months (95% CI: 9.9, NR) at 2.5 mg/kg and 
13.8 months (95% CI: 10.0, NR) at 3.4 mg/kg. Positive clinical activity was also 
demonstrated at the 3.4 mg/kg lyophilized dose [ORR 52% (97.5% CI 28.9,74.5)] [GSK 
Document Number 2013N175128 V08, 2020]. 
4.2.4.2. 
Clinical Safety in belantamab mafodotin monotherapy studies 
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 20Sep2019) for DREAMM-2 study and 
supportive FTIH study DREAMM-1 by treatment cohorts of 2.5 mg/kg and 3.4 mg/kg 
[GSK Document Number 2013N175128 V08, 2020]. 
The most common AEs in both treatment cohorts were keratopathy (corneal epithelium 
changes observed on ophthalmic examination), thrombocytopenia and anemia. The 
incidence of AEs, including Grade 3/4 AEs was comparable between belantamab 
mafodotin 2.5 mg/kg and 3.4 mg/kg cohorts. Adverse events leading to dose delays, and 
reductions were less frequent in 2.5 mg/kg cohort, 51% and 32% compared with the 3.4 
mg/kg cohort, 67% and 52%, respectively. AEs leading to permanent treatment 
discontinuation occurred in 10% and 11% of participants in the 2.5 and 3.4 mg/kg 
cohorts, respectively. More participants in the 3.4 mg/kg cohort experienced SAEs (50%) 
and fatal SAEs (6%) compared with the 2.5 mg/kg cohort (41% and 3%, respectively). 
Single agent belantamab mafodotin 2.5 mg/kg was selected as the recommended dose 
based on comparable efficacy with a more favorable safety profile (i.e. lower incidence 
of thrombocytopenia and neutropenia and less frequent dose delays or reductions) 
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Adverse Events of Special Interest 
Adverse events of special interest (AESIs) for belantamab mafodotin are corneal events, 
thrombocytopenia and infusion-related reactions, and are summarized in the IB [GSK 
Document Number 2013N175128 V08, 2020]. 
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 31Jan2020), events in the Eye disorders SOC occurred in 
78% of participants treated with belantamab mafodotin 2.5 mg/kg. The most common 
ocular AEs were keratopathy (71%, changes in corneal epithelium identified on eye 
exam, with or without symptoms), blurred vision (22%), and dry eye (13%). Decreased 
vision defined as Snellen score worse than 20/50 in the better seeing eye was reported in 
18% of participants receiving belantamab mafodotin 2.5mg/kg. Severe vision loss 
defined as 20/200 or worse in the better seeing eye was reported in 1% of participants 
receiving belantamab mafodotin 2.5 mg/kg. 
The median time to onset of Grade 2 or above corneal findings (best corrected visual 
acuity or corneal examination) was 36 days (range: 19 to 143 days) in participants 
receiving belantamab mafodotin 2.5 mg/kg. The median time to resolution of these 
corneal findings was 91 days (range: 21 to 201 days). 
Participants with history of dry eye were more prone to develop corneal examination 
findings. Therefore, active management of dry eye symptoms prior to and during 
treatment is recommended (i.e. administration of preservative-free artificial tears). 
The ocular sub-study of DREAMM-2 provided no evidence that corticosteroid eye drops 
are beneficial in preventing or mitigating corneal events. 
Thrombocytopenia 
In DREAMM-2 (data as of 31Jan2020), 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. 
Infusion-related reactions 
Infusion-related reactions (IRRs) are expected for biologic agents. In DREAMM-2 (data 
as of 31Jan2020), IRRs occurred in 21% of participants in the belantamab mafodotin 2.5 
mg/kg, which were Grade 1 - 3 in severity. Most IRRs occurred with the first infusion 
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Although not protocol-mandated, pre-medications for IRR prophylaxis (including 
paracetamol, antihistamines, and steroids) were administered to 26%–27% of 
participants. One participant (2.5 mg/kg cohort) discontinued treatment due to IRRs 
(Grade 3 IRRs at first and second infusion).  
4.2.4.3. 
Pharmacokinetics and Pharmacodynamic in Humans 
The pharmacokinetics and pharmacodynamics of belantamab mafodotin (antibody-drug 
conjugate, including complex) and total monoclonal antibody (total mAb; including 
complex) were investigated in 291 participants with RRMM following IV administration 
at doses from 0.03 to 4.6 mg/kg Q3W in Study BMA117159 (n=73) and at doses of 2.5 
or 3.4 mg/kg Q3W in Study 205678 (n=218). 
Maximum concentrations (Cmax) of belantamab mafodotin and total monoclonal 
antibody were observed at or shortly after the end of infusion (EOI). There was limited 
accumulation (less than 2-fold) of belantamab mafodotin during subsequent cycles.  
Belantamab mafodotin pharmacokinetics were well described by a linear, two-
compartment population model, with a time-varying decrease in clearance in a population 
pharmacokinetic analysis. At Cycle 1, belantamab mafodotin had a systemic clearance of 
0.924 L/day, steady-state volume of distribution of 10.8 L, and an elimination half-life of 
11.8 days in participants with RRMM in Study 205678. Over time, clearance was 
reduced to 0.725 L/day, with an elimination half-life of 14.0 days. The time to 50% 
change in clearance was approximately 50 days.  
No clinically significant differences in the pharmacokinetics of belantamab mafodotin 
were observed based on age (34 to 89 years), sex, race (African American/Black and 
White), body weight (42 to 130 kg), mild or moderate renal impairment (eGFR ≥ 
30 ml/min/1.73m2) or mild hepatic impairment (NCI-ODWG classification). Higher 
serum levels of 2-microglobulin, IgG, and 
) and lower levels of 
albumin are associated with more advanced multiple myeloma or a higher multiple 
myeloma disease burden. Higher baseline IgG and 
 levels, and lower baseline 
albumin levels were associated with higher belantamab mafodotin clearance leading to 
lower average and trough concentrations (Ctau) of belantamab mafodotin.   
In nonclinical studies, cys-mcMMAF had limited metabolic clearance.  In vitro data 
suggested that belantamab mafodotin and cys-mcMMAF are unlikely to perpetrate a 
drug-drug interaction or to be a victim of a drug-drug interaction with inhibitors or 
inducers of cytochromes (CYP) P450. Cys-mcMMAF was an in vitro substrate of organic 
anion transporting polypeptides (OATP)1B1 and OATP1B3, multidrug resistance 
associated proteins (MRP)1, MRP2, and MRP3, a borderline substrate of bile salt export 
pump (BSEP), and a possible substrate of P-glycoprotein (P-gp). Following the 
administration of belantamab mafodotin to participants with RRMM, only intact cys-
mcMMAF was detected in pooled human urine, with no evidence of other MMAF-
related urinary metabolites.  
Free
 levels were measured in Study BMA117159 and Study 205678.  All 
subjects exhibited reductions in free 
 concentration at end of infusion compared 
to baseline at Cycle 1, with a return to near-baseline level by seven days after dosing, 
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reflecting binding of belantamab mafodotin to 
.  Maximum decreases ranged 
from 2% to 97%, which were qualitatively dose-dependent, with larger reductions in free 
 at higher doses.  
Exposure-response analyses performed for Study 205678 and/or Study BMA117159 
found that ocular safety endpoints were most strongly associated with belantamab 
mafodotin exposure, while efficacy endpoints had a weaker association with belantamab 
mafodotin exposure. Both safety and efficacy endpoints were associated with patient 
characteristics. Belantamab mafodotin Ctau was associated with probability of corneal 
events and keratopathy. Probability of occurrence of dry eye, blurred vision, neutropenia 
and infusion related reaction were not associated with an exposure measure. In addition, 
the results of the concentration-QTc analysis demonstrated that belantamab mafodotin 
did not have a significant effect on cardiac repolarization. 
Additional information related to belantamab clinical PK, PD, and exposure-response 
relationships can be found in the Investigator’s Brochure [GSK Document Number 
2013N175128 V08, 2020] 
4.2.4.4. 
Clinical Summary 
These results suggest that belantamab mafodotin has an acceptable safety profile and 
demonstrates significant clinical activity in RRMM that warrants further exploration in 
combinations with SoC. 
Additional summaries of nonclinical and clinical findings and information regarding 
warnings, precautions, contraindications, adverse events, and other pertinent information 
on belantamab mafodotin that may impact participant eligibility are provided in the 
Investigator’s Brochure [GSK Document Number 2013N175128 V08, 2020].  
4.3. 
Benefit/Risk Assessment 
4.3.1. 
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 
Investigator’s Brochure; more detailed information on lenalidomide, bortezomib, or 
dexamethasone may be found in their respective package inserts, provided in the SRM.  
 
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Table 11 
Summary of Risk Assessment for the Combination Therapy of Belantamab Mafodotin with Len/Dex (Arm A) and 
Belantamab Mafodotin with Bor/Dex (Arm B) 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
 
Thrombocytopenia 
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. 
 
Routine monitoring of hematologic panels as outlined in the SoAs. 
Supportive therapy per local medical practice (e.g., platelet transfusion). 
Dose modification guidelines are outlined in Section 8.2. 
Pneumonitis 
Non-clinical safety experiments have demonstrated the presence of 
progressive microscopic changes in the lungs (prominent alveolar 
macrophages associated with eosinophilic material; mixed 
perivascular/neutrophilic inflammation) in rats at all doses tested. 
Cases of pneumonitis, including fatal events, have been observed with 
belantamab mafodotin although a causal association has not been 
established. 
 
Monitoring for clinical signs and symptoms related to pulmonary toxicity.  
If a participant experiences new or worsening pulmonary symptoms, (e.g., 
cough, dyspnea) without obvious etiology, further diagnostic tests and 
management should be performed as described in Section 8.2 and further 
treatment with belantamab mafodotin delayed (refer to Section 8.2). 
An overall benefit/risk assessment should be considered for the participant 
prior to continuing belantamab mafodotin treatment. 
Further diagnostic tests and management will be implemented immediately 
in cases of suspected pneumonitis as described in Table 16.  


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Increased Infections 
due to 
Immunosuppression or 
neutropenia 
In non-clinical studies, belantamab mafodotin has been associated with 
decrease in immunoglobulins in monkeys, at all doses. An increase in 
immunoglobulins was seen in rats (rats are not an antigen-specific 
species for belantamab mafodotin). 
Immunosuppression is frequently associated with an increased risk of 
infection. Serious and non-serious infections have been reported in 
belantamab mafodotin studies, including respiratory infections, 
pneumonia, and sepsis. 
Neutropenic events, including febrile neutropenia have been observed 
with belantamab mafodotin. 
In a study of belantamab mafodotin in combination with lenalidomide / 
dexamethasone, two fatal cases of severe infections associated with 
neutropenia were observed. Arm A subjects include belamaf,+len/dex. 
Participants with an active infection are excluded. 
Monitoring for infections and immediate treatment of immunosuppression 
according to standard practice. 
Routine monitoring of hematologic panels as outlined in the SoA. 
Supportive therapy per local medical practice (e.g. growth factors). 
Prophylactic antibiotics, per local institutional guidance, in participants with 
Grade 3-4 neutropenia. 
Immediate hospitalization of participants with febrile neutropenia. 
Dose modification guidelines are outlined in Section 8.2 
Keratopathy (changes 
to the corneal 
epithelium, potentially 
resulting in vision 
changes) 
Changes in corneal epithelium on ocular examination have been 
frequently observed with belantamab mafodotin and was most commonly 
associated with keratopathy (changes in the corneal epithelium upon 
examination), 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. 
Active monitoring of the corneal epithelium and visual acuity as outlined in 
the SoA. 
Evaluation and management by an eye care professional. 
Dose modification guidelines are outlined in Section 8.2. 


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Based on available follow-up data, vision returned to, or near, baseline in 
most cases. 
 
Infusion-Related 
Reactions (IRRs) 
IRRs were reported in participants treated with belantamab mafodotin. 
Most IRRs were Grade 1-2 and manageable with medical treatment. 
Close monitoring for signs of IRR. 
Consider premedication for IRR in participants at risk. 
If an IRR occurs, follow the guidance in Section 8.2. 
Nephrotoxicity 
Non-clinical safety experiments have demonstrated primary glomerular 
injury and tubular degeneration/regeneration (in rat and monkey). These 
morphologic changes were accompanied by large molecular weight 
proteinuria (albuminuria) and enzymuria. Single cell necrosis of the 
kidney and bladder urothelium was also noted in the chronic study. The 
renal changes were dose dependent and reversible. Severe tubular 
degeneration/regeneration and marked glomerulonephritis as a result of 
immune complex disease associated with ADA led to the early 
euthanasia of 1 monkey following 5 weekly doses of 10 mg/kg. 
Increased albumin/creatinine ratio (albuminuria) has been reported in 
participants receiving belantamab mafodotin not indicative of disease 
progression and, in such cases, appropriate monitoring and dose 
modification should be considered. 
Kidney function monitoring including albumin/creatinine ratio (ACR). 
Education of participants on the need to maintain adequate urinary output. 
Dose modification guidelines for increased serum creatinine and urinary 
albumin/creatinine ratio are outlined in Section 8.2. 
 
 


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4.3.2. 
Benefit Assessment 
As of 31 August 2018, results from the FTIH Study BMA117159 indicate that 
belantamab mafodotin monotherapy administered at 3.4 mg/kg (n=35) is active in the 
MM participant population and demonstrated an ORR of 60% with a 95% confidence 
interval (CI of 42.1% to 76.1%) and median PFS of 12 months.  Preliminary data from 
the on-going Phase II study 205678 indicate that both dose levels of belantamab 
mafodotin (2.5 and 3.4 mg/kg) have a positive benefit/risk profile. The dose of 2.5 mg/kg 
appears to have a lower incidence of adverse events and less frequent dose delays and 
reductions, and it results in similar efficacy with 3.4 mg/kg dose as measured by ORR. 
The combination treatment of the highly active drug belantamab mafodotin with SoC is 
expected to result in improved outcomes, and to provide additional control of symptoms 
or disease progression.  It is reasonable to hypothesize that such combination will benefit 
MM participants, who are refractory to currently available treatments. 
4.3.3. 
Overall Benefit:Risk Conclusion 
As of Amendment 03 there is limited clinical experience with the combination of 
belantamab mafodotin with Len/Dex and Bor/Dex. Preliminary safety data from Arm B 
of 207497 suggests that the combination of belantamab mafodotin 2.5 mg/kg IV Q3W 
with standard doses of bortezomib and dexamethasone has an acceptable safety profile, 
consistent with individual components. Belantamab mafodotin is a highly active agent in 
RRMM [Trudel, 2019; Lonial, 2020]. Taking into account the measures to minimize risks 
to participants in this study, the potential risks identified in association with belantamab 
mafodotin in combination with Len/Dex and Bor/Dex are justified by the anticipated 
benefits that may be afforded to participants with RRMM.  
5. 
OBJECTIVES AND ENDPOINTS 
The purpose of this Phase I/II dose escalation/dose expansion study is to determine if 
belantamab mafodotin can be safely administered in combination with two approved SoC 
regimes treatments for RRMM (Len/Dex or Bor/Dex in Part 1). The objective of Part 2 is 
to further evaluate the safety and preliminary clinical activity of selected doses of 
belantamab mafodotin with Len/Dex or Bor/Dex to identify the optimal dose(s) and 
schedule for each arm of combination treatment of belantamab mafodotin when 
administered with Len/Dex, or Bor/Dex. 
The primary, secondary, and exploratory objectives, along with the corresponding 
endpoints for study 207497 are listed in Table 12. 


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Table 12 
Objectives of Study 207497 – Dose Escalation and Dose Expansion 
Objectives 
Endpoints 
Primary 
Dose Escalation 
Determine safety, tolerability of belantamab 
mafodotin in combination with either Len/Dex 
(Arm A) or Bor/Dex (Arm B) to establish a 
recommended dose range and schedule to 
evaluate in Dose Expansion for participants with 
RRMM 
 
Dose Escalation and Expansiona 
Select the dose(s) and dosing schedule for 
further investigation based on safety and 
tolerability of belantamab mafodotin in 
combination with either Len/Dex (Arm A) or 
Bor/Dex (Arm B) for participants with RRMM     
 
Number (%) of participants with DLTs. 
Number (%) of participants with AEs, 
changes in clinical signs and laboratory 
parameters. 
 
 
 
A comprehensive determination based on 
safety and SAE/AEs. 
Dose Expansion 
To determine preliminary clinical activity of 
belantamab mafodotin in combination with either 
Len/Dex (Arm A) or Bor/Dex (Arm B) for 
participants with RRMM     
 
A specific determination based on ORR 
defined as percentage (%) of participants 
achieving PR as defined by the IMWG 
Uniform Response Criteria for MM [Kumar, 
2016]. 
Secondary 
Dose Escalation and Expansion 
To evaluate the pharmacokinetics profile of 
belantamab mafodotin when administered in 
combination with Len/Dex (Arm A) or Bor/Dex 
(Arm B) in participants with RRMM 
Belantamab mafodotin PK parameters, as 
data permit  
To evaluate the pharmacokinetics profile of 
lenalidomide when administered in combination 
with belantamab mafodotin and dexamethasone 
Lenalidomide PK parameters, as data permit 
in Cycle 1 
To evaluate the pharmacokinetics profile of 
bortezomib when administered in combination 
with belantamab mafodotin and dexamethasone 
Bortezomib PK parameters, as data permit in 
Cycle 1 
To assess anti-drug antibodies (ADAs) against 
belantamab mafodotin 
Incidence and titers of ADAs against 
belantamab mafodotin pre-dose in Cycle 1 
and selected subsequent cycles 
To evaluate the effect and tolerability of 
belantamab mafodotin in combination with 
Len/Dex (Arm A) or Bor/Dex (Arm B) on 
Changes from baseline in symptoms and 
related impacts as measured by OSDI, NEI-
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Objectives 
Endpoints 
symptomatic adverse events in participants with 
RRMM 
To further characterize safety of belantamab 
mafodotin administered in combination with 
Len/Dex (Arm A) or Bor/Dex (Arm B) in 
participants with RRMM 
Incidence of AEs, including SAEs and AEs of 
special interest (corneal events, 
thrombocytopenia and infusion related 
reactions). 
 
Ocular findings on ophthalmic exam 
To evaluate the effect of belantamab mafodotin 
in combination with Len/Dex (Arm A) or Bor/Dex 
(Arm B) on health-related quality of life in 
participants with RRMM 
Changes from baseline in health-related 
quality of life as measured by the EORTC 
QLQ-C30 and QLQ-MY20 
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6. 
STUDY DESIGN 
6.1. 
Overall Design 
Part 1 of the study is a dose escalation phase to evaluate the safety and tolerability of up 
to 3 dose levels and up to 2 dosing schedules of belantamab mafodotin in combination 
with two SoC regimens (Arm A - belantamab mafodotin with Len/Dex [Figure 1] and 
Arm B - belantamab mafodotin with Bor/Dex [Figure 2]).   
Part 2: 
For Arm A (belantamab mafodotin with Len/Dex): Part 2 of the study will further 
evaluate the safety and preliminary clinical activity of up to 2 dose levels and up to 3 
dosing schedules of belantamab mafodotin with Len/Dex (Table 18). Additional dosing 
schedules may be considered if subsequent analyses of PK properties and the emerging 
safety profile support the exploration. Preclinical data with belantamab mafodotin 
suggest significantly greater activity when combined with lenalidomide in in vitro and in 
vivo in two established MM xenograft models [GSK internal data].  We hypothesize that 
the clinical combination of belantamab mafodotin with len/dex may result in significantly 
greater activity than that seen with the individual components. Given this and the 
emerging preliminary clinical data from evaluation of 2.5 mg/kg dosing cohorts in 
amendment 2, for Arm A, the maximum planned dose of belantamab mafodotin is 2.5 
mg/kg and higher doses will not be investigated in this Arm. However, an alternate 
dosing schedule of STRETCH (Q8W) dosing may be explored for the 1.9 mg/kg dose 
level if emerging data (from either this study or across the program) suggests that this 
schedule may further optimize the tolerability or offers an improved benefit/risk profile. 
For Arm B (belantamab mafodotin with Bor/Dex): Part 2 of the study will further 
evaluate the safety and preliminary clinical activity of up to 3 dose levels and up to 4 
dosing schedules of belantamab mafodotin with Bor/Dex (Table 18). Additional dosing 
schedules may be considered if subsequent analyses of PK properties and the emerging 
safety profile support the exploration. For Arm B, the maximum planned dose of 
belantamab mafodotin is 3.4 mg/kg, and higher doses will not be investigated in this 
study.  
Administration of belantamab mafodotin at 2.5 mg/kg (Arm A & Arm B) and 3.4 mg/kg 
(Arm B only) as a SINGLE dose was tested in Protocol Amendment 1. It is hypothesized 
that the administration of belantamab mafodotin split into two equal halves with each half 
dose administered on Day 1 and Day 8 of each cycle could result in improvement of 
benefit/risk due to ~25% reduction in the maximum concentration while maintaining 
similar exposure over a cycle compared to the administration of a full dose on Day 1. To 
facilitate this, SPLIT dosing at the 3.4 mg/kg dose level (administering 1.7 mg/kg of 
belantamab mafodotin each at Day 1 and Day 8 of each dosing cycle) was introduced 
with Amendment 2 to deliver the same AUC of the dose with lowering of the Cmax. 
Accordingly, in addition to the planned 2.5 mg/kg SINGLE dosing of belantamab 
mafodotin, 2.5 mg/kg SPLIT dosing at belantamab mafodotin (administering 1.25 mg/kg 
of belantamab mafodotin each at Day 1 and Day 8 of each dosing cycle) is being tested 
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Amendment 3 to help explore alternative dosing schedules in order to optimize the 
administration of belantamab mafodotin in combination with SoC.  
Although in Amendment 2, it was planned to test the 3.4 mg/kg dose as both SINGLE & 
SPLIT doses for Arm A, as described above, preclinical data from xenograft mouse 
models and emerging clinical data from Arm A in Amendment 2 suggests greater activity 
of belantamab mafodotin in combination with lenalidomide. Given this, in Amendment 3, 
the maximum planned dose of belantamab mafodotin in combination with 
lenalidiomide/dexamethasone in Arm A is 2.5 mg/kg and higher doses will not be 
investigated in Arm A. 
For Arm B, however, with Amendment 3, to reduce increased exposure over time and 
potentially improve the benefit/risk for the participants, an extended inteval of 6 weeks 
(STRETCH schedule) between 2 consecutive planned doses of belantamab mafodotin 
will be evaluated in Arm B Part 2. As 6 weeks represents 3 half-lives of belantamab 
mafodotin, it is anticipated to lead to minimal accumulation. In addition, a Step-Down 
(S/D) STRETCH schedule with a first dose of 2.5 mg/kg at Cycle 1 Day 1 followed by 
1.9 mg/kg every 6 weeks (42 [ 3] days) from Cycle 3 onwards will also be studied as an 
alternative to 2.5 mg/kg repeating every 6 weeks (42 [3] days). Similarly, dosing 
cohorts evaluating belantamab mafodotin 1.9 mg/kg dose every 3 weeks (1.9 mg/kg 
SINGLE) and 1.9 mg/kg dose every 6 weeks (1.9 mg/kg STRETCH) are also being 
introduced in Amendment 3.   
For participants who discontinue study treatment for reasons other than PD, disease 
evaluations will continue to be performed at every 28 days (±3 days) for Arm A 
(belantamab mafodotin with Len/Dex) and at every 21 days (±3 days) for Arm B 
(belantamab mafodotin with Bor/Dex), until confirmed PD, death, start of a new 
anticancer treatment, withdrawal of consent, or end of the study, whichever occurs first. 
After PD is documented, participants will continue to be followed for survival and 
subsequent anticancer therapy every 3 months (±7 days) until the study ends. 
Following 12 months post last subject first dose (LSFD), DREAMM-6 study will move 
into the post analysis continued treatment (PACT) phase. At that time, the collection of 
new data for all recruited participants who no longer receive study treatment will stop 
entirely and the clinical trial database will be closed. Those participants still benefiting 
from study drug in the opinion of their treating physician may continue to receive study 
drugs. In case the participant meets stopping criteria for belantamab mafodotin, the 
participant will discontinue all treatment and will continue to be monitored as per 
standard of care at the participant’s particular study site. Only SAEs, AEs leading to 
treatment discontinuation, overdose and pregnancy cases, and pre-specified ocular data 
will be reported directly to GSK.  
6.1.1. 
Arm A - Belantamab Mafodotin with Len/Dex 
6.1.1.1. 
Part 1 Dose Escalation Phase 
The modified Toxicity Probability Interval (mTPI) design [Ji, 2010] will be used to guide 
dose escalation in Part 1 with a slight modification (Figure 1). Up to 2 dose levels of 
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schedules are planned to be evaluated in combination with the fixed dose of the Len/Dex 
treatments. Based on emerging data under Protocol Amendment 1 from Arm A, the first 
dose investigated under Protocol Amendment 2 was 1.9 mg/kg (Dose Level -1). The 
design assumes the true underlying toxicity rate for maximum tolerated dose (MTD) of 
belantamab mafodotin falls within the range from 25% to 35% and centers at 30%.  The 
rules for guiding dose escalations are provided in Figure 4. Columns provide the numbers 
of participants treated at the current dose level, and rows provide the corresponding 
numbers of participants experiencing toxicity. Cohorts will be recruited in blocks of three 
participants. Participants will be treated in a staggered approach with at least 1 day 
between each participant’s first dose of belantamab mafodotin to minimize the risk of 
inadvertently exceeding the MTD in multiple participants.  
In Part 1 up to 2 dose levels of belantamab mafodotin and up to 2 dosing schedules will 
be evaluated (Figure 1 and Table 13). Data from at least 3 DLT-evaluable participants are 
required before a decision is made to escalate to the next dose level. However, this is not 
required for enrollment of more participants at the same dose level in Part 2.   
 
Figure 4 
Dose-finding Criteria for the Modified Toxicity Probability Interval 
(mTPI) Dose-Finding Method 
Number of DLTs 
Number of Subjects treated at current dose 
1 
2 
3 
4 
5 
6 
0 
E 
E 
E 
E 
E 
E 
1 
D 
S 
S 
S 
S 
E 
2 
DU 
D 
S 
S 
S 
3 
DU 
DU 
D 
S 
4 
DU 
DU 
DU 
5 
DU 
DU 
6 
DU 
The spreadsheet was generated based on a beta/binomial model and precalculated before trial initiation.  The letters in 
different colors are computed based on the decision rules under the mTPI method and represent different dose-finding 
actions.  In addition to actions de-escalate the dose (D), stay at the same dose (S), and escalate the dose (E), the 
table includes action unacceptable toxicity (DU), which is defined as the execution of the dose-exclusion rule in mTPI.  
Excerpted from Ji, et al. [Ji, 2010]. 
The entries of Figure 4 are dose-finding decisions (i.e., E, S, and D) representing 
escalating the dose, staying at the same dose, and de-escalating the dose.  In addition, 
decision DU means that the current dose level is unacceptable because of high toxicity; 
the current dose level and any higher dose level should be excluded from the trial.   
For example, when 1 of 3 participants experiences toxicity, the decision can be located at 
row 1 and column 3, which is S – to stay at the current dose level.  Consequently, the 
next cohort of participants will be treated at the same dose level currently being used.  If 
zero of three participants experience toxicity, the decision is at row 0 and column 3, 
which is E – to escalate.  Thus, the next cohort of participants will be treated at the next-
higher dose level.  If 3 of 3 participants experience toxicity, the decision is DU – to de-
escalate to the next-lower dose level and exclude the current dose and any higher dose 
from the trial, because toxicity levels are unacceptable. In dose escalation (E)/de-
escalation (D), no dose skipping is allowed. 


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Table 13 
Dose Levels: Arm A, Part 1 
Dose Level 
Belantamab mafodotin 
Lenalidomide 
Dexamethasone 
Permissible 
Actions 
Increase/Decrease 
No changes 
No changes 
Dose Level -1 
(de-escalation) 
1.9 mg/kg IV q28 days 
25 or 10 mg PO, QD on 
Days 1 to 21 of each 28-
day cycle 
40 or 20 mg/week PO or 
IV on Days 1, 8, 15, and 
22 of each 28-day cycle 
Dose Level 1 
2.5 mg/kg IV q28 daysa 
25 or 10 mg PO, QD on 
Days 1 to 21 of each 28-
day cycle 
40 or 20 mg/week PO or 
IV on Days 1, 8, 15, and 
22 of each 28-day cycle 
IV = intravenous; PO = orally; QD = once daily; SC = subcutaneous 
Alternate dosing schedule could be investigated such as 2.5 mg/kg SPLIT dosing schedule where belantamab 
mafodotin will be administered at 1.25 mg/kg each on Day 1 and Day 8 
 
Any participant from Part 1 in Arm A who received at least 1 full dose of belantamab 
mafodotin and at least 75% of planned doses of Len/Dex by the end of Cycle 1 (Day 28 
for Arm A) is considered DLT-evaluable. Participants in Part 1 who have received less 
than 1 full dose of belantamab mafodotin, or <75% of planned doses of Len/Dex, or who 
have been withdrawn from the study for reasons other than toxicity but prior to 
completion of DLT observation period will be replaced.   
Part 1 starts with a cohort of 3 participants at a dose level of 1.9 mg/kg SINGLE. Safety 
data over the first cycle of treatment for each participant will be evaluated. Data from at 
least 3 DLT evaluable-participants are required before a decision is made to escalate to 
the next dose level. The study will enroll participants in Part 1 will have staggered start 
times, but will run simultaneously as outlined below. If dose levels are open for both Part 
1 and Part 2, priority for enrollment will be given to Part 1. 
 
Rules for of mTPI dose escalation pertaining to Arm A only: 
• If dose escalation decision is E, enrollment for Part 1 will be open at 2.5 mg/kg 
SINGLE and 2.5 mg/kg SPLIT. At the same time, Part 2 expansion could be 
opened to enroll additional participants at 1.9 mg/kg SINGLE. 
• If dose escalation decision is S, three additional participants will be enrolled at 
1.9 mg/kg SINGLE in Part 1 to achieve at least 6 DLT-evaluable participants at 
1.9 mg/kg SINGLE. After review of data from the 6 participants: 
o If dose escalation decision is E, 2.5 mg/kg SINGLE and 2.5 mg/kg SPLIT 
will be open for enrollment in Part 1. Part 2 expansion will not be open for 
the 1.9 mg/kg SINGLE dose level unless emerging data suggest 2.5 mg/kg 
SINGLE and 2.5mg/kg SPLIT are not tolerable. 
o If dose escalation decision is S, enrollment will not open for dose levels 
higher than 1.9 mg/kg SINGLE in Part 1. Part 2 expansion will be open to 
enroll additional participants at 1.9 mg/kg SINGLE.  
o If dose escalation decision is D or DU, no more participants will be 
enrolled at 1.9 mg/kg SINGLE or higher dose levels in Part 1.  
Once the 2.5 mg/kg SINGLE and 2.5 mg/kg SPLIT cohorts are open for enrollment in 
Part 1, a cohort of at least 3 participants will be enrolled for each dose. When Part 1 is 


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filled, Part 2 expansion will open for enrollment at 2.5 mg/kg SINGLE and 2.5 mg/kg 
SPLIT. Data from at least 6 DLT-evaluable participants at 2.5 mg/kg SINGLE and 2.5 
mg/kg SPLIT are not required for enrollment of additional participants in Part 2. 
Operating characteristics of the dose escalation rules are shown in Table 14. 
 


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Table 14 
Operating Characteristics of the Dose Escalation Rules for Arm A 
 
Underlying True Toxicity Rate 
Average n. of participants dosed at each dose 
level1 
Prob. of Selecting as MTD2 
Scenario 
1.9 SINGLE 
2.5 SPLIT 
2.5 SINGLE 
1.9 SINGLE3 
2.5 SPLIT 
2.5 SINGLE 
<1.9 
1.9 SINGLE 
2.5 SINGLE / 
2.5 SPLIT 
1 
0.2 
0.30 
0.30 
11 
9 
9 
0.11 
0.23 
0.66 
2 
0.2 
0.30 
0.35 
11 
9 
9 
0.11 
0.25 
0.64 
3 
0.2 
0.40 
0.40 
11 
8 
8 
0.11 
0.31 
0.58 
4 
0.2 
0.40 
0.45 
11 
9 
9 
0.11 
0.34 
0.56 
5 
0.3 
0.40 
0.40 
10 
6 
6 
0.23 
0.37 
0.40 
6 
0.3 
0.40 
0.45 
10 
6 
6 
0.23 
0.38 
0.39 
7 
0.1 
0.30 
0.30 
12 
11 
11 
0.03 
0.13 
0.84 
8 
0.1 
0.25 
0.30 
12 
11 
11 
0.03 
0.11 
0.86 
9 
0.1 
0.25 
0.25 
12 
11 
11 
0.03 
0.10 
0.87 
10 
0.1 
0.20 
0.20 
12 
11 
11 
0.03 
0.08 
0.89 
11 
0.1 
0.20 
0.25 
12 
11 
11 
0.03 
0.09 
0.88 
Red: Dose too toxic/n of participants exposed to a toxic dose/prob. of selecting toxic dose as MTD 
Blue: True MTD dose/prob. of selecting true MTD as MTD 
1. 
Average n. of participants dosed at each dose level include n. of participants dosed in Part 2 assuming participants for each dose level in Part 2 are enrolled before dose 
escalation decision is made in Part 1, except for dose 1.9 mg/kg, for which Part 2 will not open for enrollment prior to dose escalation decision. 
2. 
Based on participants enrolled in Part 1 and assume the underlying true MTD is 30%.  
3. 
Number in this column represents maximum estimate where dose is escalated to 2.5 mg/kg but is de-escalated to 1.9 mg/kg based on Part 1 and Part 2 data from 2.5 mg/kg. 
 


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6.1.1.2. 
Dose Escalation Decisions 
During Part 1, the decisions on dose escalation will be made based on the mTPI 
guidance, as well as the totality of the safety, pharmacokinetics data as appropriate. The 
decisions will occur following review of all available data including participants data 
from Part 2 and joint discussion by the GSK medical monitor, participating investigators, 
and others as described in the Dose Escalation Plan. 
The GSK study team, which includes but is not limited to, the GSK medical monitor, 
clinical scientist, safety physician, statistician and clinical pharmacologist, will review 
critical safety data defined in the Dose Escalation Plan prior to making a recommendation 
for dose escalation. This includes review of all adverse events including non-DLT 
toxicities, laboratory assessments and other defined safety evaluations, as well as PK 
and/or PD data, when appropriate. The results from the mTPI method will be included in 
the decision for dose modification as described in Section 12.4.8.  Quality control of 
critical safety data will be described in the Dose Escalation Plan, which includes ongoing 
study monitoring visits, GSK review of the clinical database, and confirmation by 
participating investigators and/or delegate that the data are accurate and complete prior to 
making dose modification decisions.   
The GSK medical monitor, in joint discussion with participating investigators, and others 
as described in the Dose Escalation Plan will be responsible for making dose escalation 
decisions.  The dose-escalation decision and rationale for each cohort will be discussed 
with investigators during teleconference(s) and documented in writing, with copies 
maintained at each study site and in the study master file. 
6.1.1.3. 
Part 2 Dose Expansion 
Once Part 2 expansion is open for the 2.5 mg/kg SINGLE and 2.5 mg/kg SPLIT dose 
levels, up to 9 participants will be enrolled at each dosing schedule, unless enrollment is 
stopped based on emerging data. 
In addition, up to 12 more participants maybe potentially enrolled to evaluate an extended 
(STRETCH) dosing schedule for belantamab mafodotin at the 1.9 mg/kg dose level if 
emerging data suggests that this schedule may further optimize the tolerability or offers 
an improved benefit/risk profile. 
For STRETCH Dosing Schedule, belantamab mafodotin will be administered FIRST 
(prior to Len/Dex) as a single dose on Day 1 of every alternate 28-day cycle (C1, C3, C5, 
C7 and so on) as a 30-60 min infusion, followed by 1 to 2 h rest period. If a planned dose 
of belantamab mafodotin was held/missed due to any reason, the next dose can be 
administered at Day 1 of the next planned 28-day cycle, as long as the interval between 2 
consecutive doses is at least 56 (3) days.  
Safety data from all enrolled participants will be closely monitored while the study is 
ongoing. In addition, participants permanently discontinuing study treatment within the 
first two cycles due to AEs related to belantamab mafodotin will be continuously 
monitored starting from when 5 participants are dosed at each dose level following pre-


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defined safety stopping rules (Section 12.4.8.1). If safety concerns arise at a dose level, 
enrollment will stop for that dose level and higher dose level(s). 
6.1.2. 
Arm B - Belantamab Mafodotin with Bor/Dex 
6.1.2.1. 
Part 1 Dose Escalation Phase 
A mTPI design will be implemented [Ji, 2010] to guide dose escalation in Part 1. Up to 3 
dose levels of belantamab mafodotin (2.5 mg/kg [dose 1]; 3.4 mg/kg [dose +1]; 1.9 
mg/kg [dose -1]), starting with 2.5 mg/kg, are planned to be evaluated in combination 
with the fixed dose of Bor/Dex. Cohorts will be recruited in blocks of three participants. 
Participants will be entered in a staggered approach with at least 1 day between each 
participant’s first dose of belantamab mafodotin to minimize the risk of inadvertently 
exceeding the maximum tolerated dose (MTD) in multiple participants. A maximum of 6 
participants will be assigned to each dose (Table 15). 
Table 15 
Dose Levels: Arm B, Part 1 
Treatment Group 
and Dose Level 
Belantamab mafodotin 
Bortezomib 
Dexamethasone 
Permissible 
Actions 
Increase/Decrease 
No changes 
No changes 
Dose Level -1 
(de-escalation) 
1.9 mg/kg IV q21 days 
1.3 mg/m2 SC/IV on 
Days 1, 4, 8, and 11 of 
every 21-day cycle for a 
total of up to 8 cycles 
20 mg PO or IV on Days 
1, 2, 4, 5, 8, 9, 11, and 12 
of every 21-day cycle for 
a total of up to 8 cycles. 
Dose Level 1 
Cohort 
2.5 mg/kg IV q21 daysa 
1.3 mg/m2 SC/IV on 
Days 1, 4, 8, and 11 of 
every 21-day cycle for a 
total of up to 8 cycles 
20 mg PO or IV on Days 
1, 2, 4, 5, 8, 9, 11, and 12 
of every 21-day cycle for 
a total of up to 8 cycles. 
Dose Level +1 
Cohort 
3.4 mg/kg IV q21 daysb 
1.3 mg/m2 SC/IV on 
Days 1, 4, 8, and 11 of 
every 21-day cycle for a 
total of up to 8 cycles 
20 mg PO or IV on Days 
1, 2, 4, 5, 8, 9, 11, and 12 
of every 21-day cycle for 
a total of up to 8 cycles. 
IV = intravenous; PO = orally; QD = once daily; SC = subcutaneous 
a. 
Alternate dosing schedule could be investigated such as SPLIT dosing schedule where belantamab mafodotin 
will be administered at 1.25 mg/kg each on Day 1 and Day 8 
b. 
Alternate dosing schedule could be investigated such as SPLIT dosing schedule where belantamab mafodotin 
will be administered at 1.7 mg/kg each on Day 1 and Day 8 
 
Evaluation of the available safety data over the first cycle of treatment for each 
participant enrolled in that dose level is required from at least 3 participants before a 
decision is made to enroll additional participants at the same or the subsequent dose level. 
However, this is not required for enrollment of more participants at the same dose level in 
Part 2. 
The mTPI rule applied is explained in Section 6.1.1.1. 


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An additional dose level -1 of 1.9 mg/kg may be evaluated in case the starting dose of 
2.5 mg/kg is considered not tolerated.  
Rules for mTPI dose escalation pertaining to Arm B only: 
• If 2.5 mg/kg is the current dose level and the decision is S, and if less than 6 
participants have been evaluated for DLT and the planned maximum sample size is 
not reached, an additional cohort of 3 participants will be enrolled for DLT 
evaluation. If the dose escalation decision is S after this additional cohort, dose 
escalation is complete. 
• If 2.5 mg/kg is the current dose level and the decision is U or DU, additional lower 
dose (e.g., 1.9 mg/kg) may be explored. If the dose of 1.9 mg/kg is not tolerated (i.e., 
results in excessive toxicity) the trial will be terminated early for lack of tolerability.  
• If 3.4 mg/kg is the current dose level and the decision is E or S, and if less than 6 
participants have been evaluated for DLT at the current dose, and the planned 
maximum sample size is not reached, an additional cohort of 3 participants will be 
evaluated for DLT at the current dose. If dose escalation is E or S after this additional 
cohort, dose escalation is complete.  
• Otherwise, the dose escalation will continue until the planned maximum sample size 
(12 DLT-evaluable participants for each treatment) is reached. At the end of dose 
escalation, the rule proposed by Ji, et al. [Ji, 2010] used to guide the selection of the 
estimated MTD, from dose levels at which 3 or more participants have been evaluated 
for DLT. 
During Part 1, the decisions on dose escalation will be made based on this guidance, as 
well as the totality of the safety, pharmacokinetics data as appropriate.  
The decisions will occur following review of these data and joint discussion by the GSK 
medical monitor, participating investigators, and others as described in the Dose 
Escalation Plan. 
Any participant in Arm B who received at least 1 full dose of belantamab mafodotin and 
75% of planned doses of Bor/Dex by the end of Cycle 1 (Day 21) will be evaluated for 
DLTs.  Participants who have received less than 1 full dose of belantamab mafodotin, or 
<75% of planned doses of Bor/Dex, or who have been withdrawn from the study for 
reasons other than toxicity but prior to completion of DLT observation period will be 
replaced.   
The dose escalation of belantamab mafodotin will not include doses higher than 3.4 
mg/kg. 
6.1.2.2. 
Dose Escalation Decisions 
The GSK study team, which includes but is not limited to, the GSK medical monitor, 
clinical scientist, safety physician, statistician and clinical pharmacologist, will review 
critical safety data defined in the Dose Escalation Plan prior to making a recommendation 
for dose escalation. This includes review of all adverse events including non-DLT 
toxicities, laboratory assessments and other defined safety evaluations, as well as PK 


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and/or PD data, when appropriate. The results from the mTPI method will be included in 
the decision for dose modification as described in Section 12.4.8.  Quality control of 
critical safety data will be described in the Dose Escalation Plan, which includes ongoing 
study monitoring visits, GSK review of the clinical database, and confirmation by 
participating investigators and/or delegate that the data are accurate and complete prior to 
making dose modification decisions.   
The GSK medical monitor, in joint discussion with participating investigators and GSK 
study team, will be responsible for making dose escalation decisions.  The dose-
escalation decision and rationale for each cohort will be discussed with investigators 
during teleconference(s) and documented in writing, with copies maintained at each study 
site and in the study master file. 
6.1.2.3. 
Part 2 Dose Expansion 
In Part 2 enrollment will proceed in multiple expansion cohorts to further evaluate the 
safety profile and to evaluate the preliminary clinical activity of belantamab mafodotin in 
combination with Bor/Dex at 3 dose levels and 4 dosing schedules (2.5 mg/kg SPLIT, 2.5 
mg/kg SINGLE, 3.4 mg/kg SPLIT, 3.4 mg/kg SINGLE, 2.5 mg/kg STRETCH, S/D 
STRETCH, 1.9 mg/kg SINGLE and 1.9 mg/kg STRETCH) (Figure 2).   
In Amendment 2, enrollment of each cohort was conducted by blocks of 3 participants 
each at 2.5 mg/kg SPLIT, 2.5 mg/kg SINGLE, 3.4 mg/kg SPLIT, and 3.4 mg/kg SINGLE 
with Bor/Dex for up to 12 participants each at 2.5 mg/kg SPLIT, 2.5 mg/kg SINGLE, 3.4 
mg/kg SPLIT and up to 9 participants at 3.4 mg/kg SINGLE.  
Similarly, in Amendment 3, enrollment of each cohort will be conducted by blocks of 3 
participants each in 2.5 mg/kg STRETCH, S/D STRETCH, 1.9 mg/kg SINGLE and 1.9 
mg/kg STRETCH, until approximately 12 participants are enrolled in each cohort.  
For the SINGLE dosing schedule, belantamab mafodotin will be administered as a 
SINGLE full dose on Day 1 of each 21-day cycle. For example: A 3.4 mg/kg SINGLE 
dosing schedule will administer a 3.4 mg/kg dose on Day 1 of each cycle. A 2.5 mg/kg 
SINGLE dosing schedule of belantamab mafodotin will administer a 2.5 mg/kg dose on 
Day 1 of each cycle. A 1.9 mg/kg SINGLE dosing schedule of belantamab mafodotin 
will administer a 1.9 mg/kg dose on Day 1 of each cycle 
For the SPLIT dosing schedule, belantamab mafodotin will be split into two equal halves 
and each half dose will be administered on Day 1 and Day 8 of each 21-day cycle. For 
example: A “2.5 mg/kg SPLIT” dosing schedule will administer a 1.25 mg/kg dose on 
Day 1 and a 1.25 mg/kg dose on Day 8 of each cycle. A “3.4 mg/kg SPLIT” dosing 
schedule will administer a 1.7 mg/kg dose on Day 1 and a 1.7 mg/kg dose on Day 8 of 
each cycle. 
For STRETCH Dosing Schedule, belantamab mafodotin will be administered FIRST 
(prior to Bor/Dex) as a single dose on Day 1 of every alternate 21-day cycle (C1, C3, C5, 
C7 and so on) as a 30-60 min infusion, followed by 1 to 2 h rest period. If a planned dose 
of belantamab mafodotin was held/missed due to any reason, the next dose can be 


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administered at Day 1 of the next planned 21-day cycle, as long as the interval between 2 
consecutive doses is at least 42 (3) days.  
For the S/D STRETCH schedule, belantamab mafodotin will be administered FIRST 
(prior to Bor/Dex) as a 2.5 mg/kg dose on Day 1 of Cycle 1, followed by 1.9 mg/kg S/D 
dose on Day 1 of all subsequent alternate 21-day cycles (C3, C5, C7 and so on), as a 30-
60 min infusion, followed by 1 to 2 h rest period.  
Safety data from all enrolled participants will be closely monitored while the study is 
ongoing. In addition, participants permanently discontinuing study treatment within the 
first two cycles due to AEs related to belantamab mafodotin will be continuously 
monitored starting from when 5 participants are dosed at each dose level following pre-
defined safety stopping rules (Section 12.4.8.2). If safety concerns arise at a dose level, 
enrollment will stop for that dose level and higher dose level(s).  
6.1.3. 
Criteria for Belantamab Mafodotin DLT in Part 1 
Any participant in Part 1 who received at least 1 full dose of belantamab mafodotin and 
≥75% of the planned doses of the combination with Len/Dex (Arm A), or Bor/Dex 
(Arm B) in Cycle 1 will be evaluated for DLTs using NCI-CTCAE Version 4.03 
[National Cancer Institute, 2010]. Any participant that experiences a DLT in Cycle 1 
prior to receiving a full dose of belantamab mafodotin or <75% of the respective Arm 
SoC (Len/Dex – Arm A or Bor/Dex – Arm B) will also be considered DLT-evaluable. 
Participants that are not DLT-evaluable will be replaced. 
Dose-limiting toxicity (DLT) is assessed during DLT observation period defined as 
follows:   
• 
The first 28 days (= 1 cycle) for Arm A   
• 
The first 21 days (= 1 cycle) for Arm B  
An event will be considered a DLT if it is attributed (definitely, probably, or possibly) to 
the investigational agent, occurs within the DLT reporting period, and meets one of the 
criteria provided in Table 16. 
A participant who develops a DLT will be allowed to continue on study if the toxicity did 
not meet predefined stopping criteria and recovered to Grade 1 and if the investigator 
and Medical Monitor agree that for a given participant the potential benefits may 
outweigh the risks. 
The lowest full dose of belantamab mafodotin to be evaluated in this study is 1.9 mg/kg 
IV.  If 1.9 mg/kg is not tolerated, the respective treatment arm will be closed for lack of 
tolerability.  Independent dose escalation rules will apply to each treatment arm. 


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Table 16 
Dose-Limiting Toxicity Criteria for Belantamab Mafodotin in Part 1 Cycle 1 
Criteria for Identification and Grading of Belantamab Mafodotin DLTs in Part 1 
Toxicity Type and Grade 
DLT Definition and Grade 
Hematologic 
• 
Grade 3 or greater febrile neutropenia lasting >48 h despite adequate treatment: 
• 
Grade 3 is defined as ANC <1.0×109/L with a single temperature of >38.3C (101F) or a sustained 
temperature of ≥ 38C (100.4F) for more than 1 h. 
• 
Grade 4 is defined as ANC <1.0×109/L with a single temperature of >38.3C (101F) or a sustained 
temperature of ≥38C (100.4F) for more than 1 h, with life-threatening consequences and urgent 
intervention indicated. 
• 
Grade 4 Thrombocytopenia <25,000/mm3 accompanied by clinically significant bleeding. 
Non-hematologic except 
corneal events 
• 
Any Grade 3 or greater non-hematologic toxicity (other than corneal events) which is more severe than expected 
for an individual agent * or which does not resolve with appropriate supportive treatment within 48 h 
• 
Any Grade 3 or greater non-hematologic laboratory value if  
• 
The laboratory abnormality persists for >48 h despite supportive treatment 
• 
The abnormality leads to hospitalization. 
Corneal events 
• 
Grade 4 per the GSK corneal grading scale provided in Table 33. 
Other organ-specific 
toxicities 
• 
Liver toxicity meeting prespecified GSK liver stopping criteria. 
*For a list of most frequent adverse events for belantamab mafodotin see Investigator’s Brochure, [GSK Document Number 2013N175128 V08, 2020]; for lenalidomide see Celgene 
Corporation (2019), REVLIMID Prescribing Information, and for bortezomib see VELCADE (bortezomib) Prescribing Information (2019). 


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6.2. 
Number of Participants 
Overall, it is estimated that approximately 152 treated participants will be enrolled in this 
two-part study (approximately 27 in Part 1, and approximately 125 in Part 2). 
• 
Up to 27 DLT-evaluable participants with RRMM (approximately 14 participants in 
Arm A and approximately 13 participants in Arm B) will be evaluated during the 
Part 1 dose escalation phase. 
• 
Part 2 will enroll approximately 125 participants with RRMM (approximately 31 
participants in Arm A and approximately 94 participants in Arm B) in order to 
further evaluate the safety and preliminary clinical activity of the combination 
treatments.  
At the time of Amendment 3 more participants have been added to Part 1 (Arms A and 
B) for the study due to non-DLT evaluable participants and the requirement for an 
additional replacement participant to assure an adequate assessment of DLTs. Two 
participants were added to Part 2 (Arms A and B) as a replacement for participants who 
either received an incorrect dose or failed to complete a full cycle. 
6.3. 
Participant Study Completion, Study Analysis and End of 
Study 
Participant Study Completion 
A participant will be considered to have completed the study if he or she received at least 
one dose of study treatment and has progressed or died before the end of the study, has 
not been lost to Follow-up, or has not withdrawn consent from study participation, or the 
study or a treatment arm has been terminated. 
A participant will be considered to have withdrawn from the study if the patient 
• 
has not died and is lost to Follow-up, or 
• 
has withdrawn consent, or 
• 
is no longer being followed at the investigator’s discretion 
Documentation of the cause of death in the electronic case report form (eCRF) is required 
for all participants who die in the study regardless of the cause of death. 
 
Study Analysis 
Final analysis will be conducted approximately 12 months from the last subject first visit 
(LSFV) in either arm. 
6.4. 
End of Study Definition 
Following the final analysis, the study will move into the PACT phase and the clinical 
study database will be closed to new data. Participants who are receiving belantamab 
mafodotin monotherapy or in combination with Len/Dex (Arm A) or Bor/Dex (Arm B) 
may continue to receive belantamab mafodotin monotherapy or in combination with 


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either Len/Dex (Arm A) or Bor/Dex (Arm B) if they are gaining clinical benefit as 
assessed by the investigator until they meet any criterion for permanent discontinuation 
of study intervention (see section 9 and Section 10.2). 
The end of study is defined when the last patient had their last visit (last subject last dose 
plus 70days SAE reporting period). GSK retains the right to request additional 
information for any patient with ongoing AE(s)/SAE(s) ocular data at the end of the 
study. All participants will be monitored and receive follow-up care in accordance with 
standard local clinical practice. 
6.5. 
Scientific Rationale for Study Design 
The recent addition of monoclonal antibodies (elotuzumab and daratumumab) to SoC 
treatments, such as Len/Dex or Bor/Dex has demonstrated that the results achieved can 
be improved significantly. [Lonial, 2015], [Dimopoulos, 2016].   
Belantamab mafodotin is being studied in MM participants as monotherapy in the studies 
BMA117159 and 205678. The selected RP2D of 3.4 mg/kg was considered well tolerated 
in BMA117159.  Belantamab mafodotin montherapy when used as a single agent in 
BMA117159 had an ORR of 60% (95% CI: 42.1, 76.1) and the median PFS was 12 
months [Trudel, 2018; Trudel, 2019].  In the Phase 2 study 205678 in RRMM patients, 
belantamab monotherapy showed an ORR of 31% (97.5%CI: 20.8, 42.6) [Lonial, 2020]. 
Given the previous experience with monoclonal antibodies which exhibited lower single 
agent activity as monotherapy in similar populations, the combination therapy of 
belantamab mafodotin with SoC agents is an attractive option and is expected to result in 
additive, or enhanced effects which could potentially translate into a deep and long 
lasting response over what has been achieved with available agents. 
Since belantamab mafodotin has not been combined with Len/Dex or Bor/Dex outside of 
this study, Part 1 will explore the safety and tolerability of escalating doses and alternate 
dosing schedule(s) of belantamab mafodotin administered in combination with Len/Dex 
(Arm A) or Bor/Dex (Arm B).  Part 2 will further evaluate the safety and preliminary 
clinical activity of selected doses of belantamab mafodotin with Len/Dex or Bor/Dex to 
identify the optimal dose(s) and schedule for each arm in participants with RRMM who 
have relapsed or who are refractory to at least 1 prior line of treatment. 
While there are some potential overlaps in the pattern of toxicities (primarily 
hematological) of the study treatments, these are expected to be manageable with 
appropriate supportive care. Combination therapy with these agents remains an attractive 
option to explore for the treatment of RRMM.   


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6.6. 
Dose Justification 
6.6.1. 
Starting Dose of Belantamab Mafodotin 
The starting dose for both arms of this study is 2.5 mg/kg, which is one dose level below 
the RP2D of 3.4 mg/kg for the monotherapy of belantamab mafodotin in the FTIH study 
BMA117159 when administered on a Q3W schedule. In addition to being safe and 
tolerated in a monotherapy setting, the starting dose of 2.5 mg/kg may potentially offer 
some benefit to participants if enhanced or additive effects occur with the combinations 
of belantamab mafodotin with Len/Dex or Bor/Dex, respectively. While the 2.5 mg/kg 
dose did not result in high ORR in the FTIH study BMA117159, this dose was later 
found to be effective in study 205678 with an ORR of 31% in a heavily pre-treated 
relapsed refractory patient population; 2.5 mg/kg Q3W is the proposed monotherapy dose 
for this population.  
The starting dose of 2.5 mg/kg Q3W for this combination study will allow for careful 
assessment of safety, while still providing potential benefit to participants. It is to be 
noted that a dose of 1.9 mg/kg could also provide benefit as target engagement for this 
dose was greater than 90% at the end of the first infusion based on decrease from baseline 
in serum free soluble BCMA (BMA117159). Responses have also been seen at lower 
doses of 0.96 and 1.92 mg/kg (1 out of 3 and 1 out of 4 participants respectively) in that 
study.    
Treatment in Arm B (combination with Bor/Dex) will be administered on a 21-day 
schedule which is identical as for monotherapy with belantamab mafodotin and aligned 
with dosing schedule of Bor/Dex.  
Treatment in Arm A (combination with Len/Dex) will be administered on a 28-day 
schedule. The cycle length has been adjusted to reflect the schedule of administration for 
Len/Dex. Given the mechanism of action and the fact that responses achieved with 
monotherapy with belantamab mafodotin were durable even in participants who had 
prolonged intervals between dosings due to toxicity, it is felt that a cycle length of 28 
days is appropriate for Arm A.  
For Arm A, if Dose Level -1 combination regimen (1.9 mg/kg) is tolerable, escalation to 
the higher dose of 2.5 mg/kg will proceed and additional participants will be enrolled to 
this next dose cohort.   
For Arm B, if Dose Level 1 combination regimen (2.5 mg/kg) is tolerable, escalation to 
the higher dose of 3.4 mg/kg will proceed and additional participants will be enrolled to 
this next dose cohort.   
Safety assessments and dose escalation will proceed independently for Arm A and Arm 
B. 


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6.6.2. 
Alternate Schedule for Belantamab Mafodotin 
SPLIT Dosing 
Administration of belantamab mafodotin divided as two equal administrations a week 
apart (i.e. SPLIT dosing) will be evaluated to determine if this dosing schedule results in 
an improvement to the benefit/risk due to reduction in the maximum concentration while 
maintaining similar exposure over a cycle compared to the Q3W dosing. With anticipated 
accumulation, it is predicted that a 3.4 mg/kg dose administered with a SPLIT dosing of 
1.7 mg/kg on Day 1 and Day 8 will lead to maximum concentration similar to the one 
observed with 2.5 mg/kg Q3W while achieving the same exposure (AUC) as 3.4 mg/kg 
Q3W. 
STRETCH and S/D STRETCH Schedule: 
Based on the population pharmacokinetics performed on the DREAMM-1 and 2 studies, 
belantamab mafodotin clearance decreases over time with an elimination half-life of 14 
days after repeated administration. This leads to a moderate accumulation over time. It 
has been noted that safety events related to corneal toxicity occurred more frequently 
after repeated administration than after the first dose and tended to still occur after 
repeated administration at a reduced dose. These findings may be related to the long half-
life and the decrease in clearance over time, both leading to drug accumulation. 
To reduce increased exposure over time and potentially improve the benefit/risk, an 
extended interval of every 8 weeks for Arm A or 6 weeks for Arm B (STRETCH 
schedule) will be evaluated; 6-8 weeks represents 3-4 half-lives and is anticipated to lead 
to minimal accumulation. In addition, in Arm B, a S/D STRETCH schedule with a first 
dose of 2.5 mg/kg followed by 1.9 mg/kg every 6 weeks from Cycle 3 onwards will also 
be studied as an alternative to 2.5 mg/kg repeating every 6 weeks. 
6.6.3. 
Standard of Care Dosing 
6.6.3.1. 
Len/Dex Dose (Arm A) 
Len/Dex will be administered at the approved and clinically used dose, and there will be 
no dose escalation for Len/Dex. Details on Len/Dex administration are provided in 
Section 8.1.1.2. 
6.6.3.2. 
Bor/Dex Dose (Arm B) 
Bor/Dex will be administered at the approved and clinically used dose, and there will be 
no dose escalation for Bor/Dex. Details on Bor/Dex administration are provided in 
Section 8.1.2.2. 


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7. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
7.1. 
Inclusion Criteria 
The study will enroll adult participants with RRMM, who have undergone autologous 
stem cell transplant (SCT), or are considered transplant ineligible, and who have been 
previously treated with at least 1 prior line of therapy, and who have documented 
evidence of disease progression during or after their most recent therapy.    
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
1. Capable of giving signed informed consent which includes compliance with the 
requirements and restrictions listed in the informed consent form (ICF) and in this 
protocol. 
2. Male or female, 18 years or older (at the time consent is obtained). 
3. Have confirmed diagnosis of Multiple Myeloma as defined by the International 
Myeloma Working Group (IMWG) [Rajkumar, 2016]. 
4. Eastern Cooperative Oncology Group (ECOG) performance status: 
• 
For Arm A only: 0 to 1 (Appendix 3, Section 14.3). 
• 
For Arm B only: 0 to 2 (Appendix 3, Section 14.3). 
5. Have undergone autologous SCT or are considered transplant ineligible. 
6. Have been previously treated with at least 1 prior line of MM therapy and must have 
documented disease progression during or after their most recent therapy. 
7. Must have at least ONE aspect of measurable disease, defined as one of the 
following:  
a. 
Urine M-protein excretion ≥200 mg/24h, or 
b. Serum M-protein concentration ≥0.5 g/dL (≥5.0 g/L), or 
c. 
Serum free light chain (FLC) assay:  involved FLC level ≥10 mg/dL 
(≥100 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65). 
8. Participants with a history of autologous stem cell transplant (SCT) are eligible for 
study participation provided the following eligibility criteria are met: 
a. 
Autologous SCT was >100 days prior to study enrollment 
b. No active bacterial, viral, or fungal infection(s) present 
c. 
Participant meets the remainder of the eligibility criteria outlined in this protocol 


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9. All prior treatment-related toxicities (defined by National Cancer Institute Common 
Toxicity Criteria for Adverse Events [NCI-CTCAE], Version 4.03, 2010) must be 
Grade 1 at the time of enrollment, except for alopecia. Participants with Grade 2 
neuropathy can be enrolled into Len/Dex treatment arm, but not into Bor/Dex 
treatment arm. 
10. Adequate organ system functions as defined by the laboratory assessments listed in 
Table 17. 
Table 17 
Adequate Organ System Function Based on Safety Assessments 
Organ System and Laboratory 
Tests 
Laboratory Values 
Hematologic 
Absolute neutrophil count (ANC)a 
 
1.5 × 109/L 
Hemoglobin a 
8.0 g/dL 
Platelets a 
75 × 109/L 
Hepatic 
Total bilirubin 
1.5 × ULN; (isolated bilirubin >1.5 × ULN is acceptable if bilirubin 
is fractionated and direct bilirubin is <35%) 
ALT 
2.5 × ULN 
Renal 
eGFRb 
40 mL/min/1.73 m2 
Spot urine (albumin/creatinine ratio 
from spot urine) 
500 mg/g (56 mg/mmol) 
Cardiac 
Left Ventricular Ejection Fraction 
(LVEF) by ECHO 
40%  
Note:  Laboratory results obtained during Screening should be used to determine eligibility criteria.  In situations 
where laboratory results are outside the permitted range, the Investigator may re-test the participant and the 
subsequent within range screening result may be used to confirm eligibility. 
a. 
Without Growth factor support for the past 14 days, excluding erythropoietin. Transfusions are allowed 
b. 
As calculated by Modified Diet in Renal Disease (MDRD) formula (Appendix 4, Section 14.4) 
 
 
11. Female Participants: 
Contraceptive use by women should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies. 
A female participant is eligible to participate if she is not pregnant or breastfeeding, and 
at least 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 (Appendix 7, Section 
14.7) during the intervention period and for 4 months after the last dose of 


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belantamab mafodotin and agrees not to donate eggs (ova, oocytes) for the purpose 
of reproduction during this period.  
The investigator should evaluate the effectiveness of the contraceptive method in 
relationship to the first dose of study intervention. 
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. 
WOCBP Participants Assigned to Arm A 
Due to lenalidomide being a thalidomide analogue with risk for embryo-fetal toxicity and 
prescribed under a pregnancy prevention/controlled distribution program, WOCBP 
participants will be eligible if they commit either to abstain continuously from 
heterosexual sexual intercourse or to use two methods of reliable birth control (one 
method that is highly effective; see Appendix 7, Section 14.7), beginning 4 weeks prior 
to initiating treatment with lenalidomide, during therapy, during dose interruptions and 
continuing for 4 weeks following discontinuation of lenalidomide treatment. Thereafter, 
WOCBP participants must use a contraceptive method that is highly effective (with a 
failure rate of <1% per year) for a further 3 months, and agree not to donate eggs (ova, 
oocytes) for the purpose of reproduction during this period. 
Two negative pregnancy tests must be obtained prior to initiating lenalidomide therapy. 
The first test should be performed within 10-14 days and the second test within 24 hours 
prior to prescribing lenalidomide therapy. 
WOCBP Participants Assigned to Arm B 
WOCBP assigned to Arm B 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 belantamab mafodotin or 7 months from the 
last dose of bortezomib, whichever is longer. 
12. Male Participants: 
Contraceptive use by men should be consistent with local regulations regarding the 
methods of contraception for those participating in clinical studies. 
Male participants are eligible to participate if they agree to the following:  
• Arm A: from the time of first dose of study until 6 months after the last dose of 
belantamab mafodotin 4 weeks after the last dose of lenalidomide, whichever is 
longer, to allow for clearance of any altered sperm: 
• Arm B: from the time of first dose of study until 6 months after the last dose of 
belantamab mafodotin or 4 months from the last dose of bortezomib (whichever is 
the longer) to allow for clearance of any altered sperm. 
Refrain from donating sperm and 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  


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OR 
• 
Must agree to use contraception/barrier as detailed below. 
Agree to use a male condom even if they have undergone a successful vasectomy and 
female partner to use an additional highly effective contraceptive method with a failure 
rate of <1% per year as described in Appendix 7, Section 14.7 when having sexual 
intercourse. Male participants should also use a condom with pregnant females. 
If the female partner of the male participant is pregnant at the time of enrollment, or 
becomes pregnant during the trial, the male participant must agree to remain abstinent (if 
it is consistent with their preferred and usual lifestyle) or use a male condom. 
7.2. 
Exclusion Criteria 
A participant will not be eligible for inclusion in this study if any of the following criteria 
apply: 
1. Systemic anti-myeloma therapy (including systemic steroids) within 14 days, or 
plasmapheresis within 7 days prior to the first dose of study drug. 
2. Use of an investigational drug within 14 days or five half-lives (whichever is longer) 
preceding the first dose of study drug.  
3. Prior treatment with a monoclonal antibody within 30 days of receiving the first dose 
of study drugs. 
4. Prior allogenic stem cell transplant.  
Note: Participants who have undergone syngeneic transplant will be allowed only if 
they have no history and no currently active, graft versus host disease (GvHD) 
5. Evidence of active mucosal or internal bleeding. 
6. Any major surgery within the last four weeks. 
7. 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 fulfill criteria given in Table 17. 
8. 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.  
9. Current active liver or biliary disease (with the exception of Gilbert’s syndrome or 
asymptomatic gallstones, or otherwise stable chronic liver disease per investigator’s 
assessment). 
10. Participants with invasive malignancies other than multiple myeloma are excluded, 
unless the second malignancy has been considered medically stable for at least 2 
years. The participant must not be receiving active therapy, other than hormonal 
therapy for this disease. 
Note: Participants with curatively treated non-melanoma skin cancer are allowed 
without a 2-year restriction.  


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11. Evidence of cardiovascular risk including any of the following: 
• 
Evidence of current clinically significant untreated arrhythmias, including 
clinically significant ECG abnormalities including 2nd degree (Mobitz Type II) 
or 3rd degree atrioventricular (AV) block. 
• 
History of myocardial infarction, acute coronary syndromes (including unstable 
angina), coronary angioplasty, or stenting or bypass grafting within 3 months 
of Screening. 
• 
Class III or IV heart failure as defined by the New York Heart Association 
functional classification system (Appendix 5, Section 14.5).  
• 
Uncontrolled hypertension. 
12. Known immediate or delayed hypersensitivity reaction or idiosyncratic reaction to 
drugs chemically related to belantamab mafodotin, or any of the components of the 
study treatment. 
13. Pregnant or lactating female. 
14. Active infection requiring treatment. 
15. Known HIV infection. 
16. 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) 
17. 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. 
Hepatitis RNA testing is optional and participants with negative Hepatitis C antibody 
test are not required to also undergo Hepatitis C RNA testing  
18. Current corneal disease except for mild punctate keratopathy (Appendix 8, Section 
14.8). 
Note: Participants with mild punctate keratopathy are allowed.   
Additional Exclusion Criteria for Participants Assigned to Arm A (belantamab 
mafodotin plus Len/Dex)     
19. Participants unable to tolerate antithrombotic prophylaxis must be excluded.  
20. Discontinuation of prior treatment with lenalidomide due to intolerable adverse 
events.  
Additional Exclusion Criteria for Participants Assigned to Arm B (belantamab 
mafodotin plus Bor/Dex)  
21. Unacceptable adverse effects from previous bortezomib treatment. 
22. Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain from previous 
bortezomib treatment. 
23. Intolerance or contraindications to anti-viral prophylaxis. 


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7.3. 
Lifestyle Restrictions 
The following lifestyle restrictions apply while the participants are in the study:  
• 
Contact lenses are prohibited while on the study treatment (from first dosing to the 
end of study treatment). Contact lens use may be restarted after the end of study 
treatment and a consultation with a qualified eye care specialist confirms there are no 
other contraindications.  Use of bandage contact lenses is permitted during study 
treatment as directed by a qualified eye care specialist. 
• 
Participants must not donate blood while receiving study treatment; Participants in 
Arm A must not donate blood for 28 days following discontinuation of lenalidomide. 
• 
Intraocular pressure may become elevated with dexamethasone treatment in some 
individuals. Intraocular pressure should be monitored. 
Injection Site: 
When bortezomib in Arm B is administered via SC injection, sites for each injection 
(thigh or abdomen) should be rotated.  New injections should be given at least one inch 
from an old site and never into areas where the site is tender, bruised, erythematous, or 
indurated. 
If local injection site reactions occur following administration of bortezomib SC in Arm 
B, a less concentrated solution (1 mg/mL instead of 2.5 mg/mL) may be administered SC.  
Alternatively, the IV route of administration should be considered. 
Meals and Dietary Restrictions 
There are no recognized dietary restrictions for the individual components of Arm A or 
Arm B. 
• 
For participants assigned to Arm A, lenalidomide capsules should be swallowed 
whole with water; the capsules should not be opened, broken, or chewed.  
Lenalidomide should be taken orally at approximately the same time each day 
[Celgene Corporation (2019), REVLIMID REVLIMID (lenalidomide) Prescribing 
Information, 2019] or most recent label. 
• 
Lenalidomide capsules contain lactose. The risk-benefit of Arm A should be 
evaluated in participants with lactose intolerance. 
Caffeine, Alcohol, and Tobacco 
No restrictions 
Activity 
No restrictions 


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7.4. 
Screen Failures 
Screen Failures are defined as participants who consent to participate in the clinical study 
but are not subsequently assigned to either Arm A or Arm B, or were assigned but did not 
receive treatment, because they did not satisfy all the Inclusion/Exclusion criteria 
provided in Section 7.   
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: the participant ID number; demography; 
eligibility (Inclusion/Exclusion criteria failed); reason for screen failure; any serious 
adverse events (SAE) related to study participation; and protocol deviations, if any. 
Individuals identified as Screen Failures may be rescreened if the failure was based on 
elements of eligibility that may change, e.g., laboratory test results.  Rescreened 
participants should be assigned a different participant number from that assigned for the 
initial screening. 
8. 
TREATMENTS 
“Study Treatment” is defined as any investigational treatment(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
8.1. 
Treatments Administered 
Details of the identity and characteristics of the individual components of the Study 
Treatments are shown in Table 19.  A summary of the treatment regimens and schedules 
is contained in Table 18. 
 


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Table 18 
Summary of Treatment Regimens and Schedules 
Treatment Arm 
Part 
Cohort 
Dose of Belantamab Mafodotin 
Schedule 
SoA  
Arm A: 28-Day Cycle 
Lenalidomide 25mg PO QD, D1-D21;  
Dexamethasone 20mg PO or IV, D1, 8, 
15, 22 
1 and 2 
2.5 mg/kg SINGLE 
 2.5 mg/kg IV  
Day 1 
Table 5 
1 and 2 
2.5 mg/kg SPLIT 
 1.25 mg/kg IV  
Day 1, 8 
Table 6 
1 
1.9 mg/kg SINGLE 
 1.9 mg/kg IV 
Day 1 
Table 5 
2 
1.9 mg/kg STRETCH 
1.9 mg/kg IV 
Day 1 in every alternate 28-day 
cycle 
Table 5 
Arm B: 21-Day Cycle 
Bortezomib 1.3mg/m2 SC or IV BIW, D1, 
4, 8, 11;  
Dexamethasone 20mg PO or IV QIW, 
D1, 2, 4, 5, 8, 9, 11, 12)  
Cycle 1-8 
Monotherapy ≥ Cycle 9 
1 and 2 
3.4 mg/kg SINGLE 
 3.4 mg/kg IV  
Day 1 
Table 7 
2 
3.4 mg/kg SPLIT 
 1.7 mg/kg IV  
Day 1, 8 
Table 8 
1 and 2 
2.5 mg/kg SINGLE 
 2.5 mg/kg IV  
Day 1 
Table 7 
2 
2.5 mg/kg SPLIT 
 1.25 mg/kg IV  
Day 1, 8 
Table 8 
2 
1.9 mg/kg SINGLE 
1.9 mg/kg IV 
Day 1 
Table 7 
2 
2.5 mg/kg STRETCH 
 2.5 mg/kg IV  
Day 1 in every alternate 21-day 
cycle 
Table 9 
2 
S/D STRETCH 
Cycle 1:  2.5 mg/kg IV STRETCH 
Cycle 3+:  1.9 mg/kg IV STRETCH 
Day 1 in every alternate 21-day 
cycle 
Table 9 
2 
1.9 mg/kg STRETCH 
1.9 mg/kg IV 
Day 1 in every alternate 21-day 
cycle 
Table 9 
 


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8.1.1. 
Belantamab Mafodotin and Len/Dex Combination (Arm A) 28-day 
Cycle: SINGLE,SPLIT, and STRETCH Schedules 
The schedules for dosing of belantamab mafodotin and Len/Dex on a 28-day schedule is 
shown in Figure 5. 
Figure 5 
Arm A: 28-day Dosing Schedules  
 
 


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8.1.1.1. 
Belantamab mafodotin  
For SINGLE day dosing schedule, belantamab mafodotin will be administered FIRST 
(prior to Len/Dex) in the clinic as a single full dose on Day 1 of each 28-day cycle as a 
30-60 minute (min) infusion, followed by a 1 to 2 h rest period. For example, a 2.5 mg/kg 
SINGLE dosing schedule will administer a 2.5 mg/kg dose on Day 1 of each cycle.  
For SPLIT day dosing schedule, belantamab mafodotin will be administered FIRST 
(prior to Len/Dex) in the clinic in two equal divided doses - one on Day 1 and the other 
on Day 8 of each 28-day cycle as a 30-60 min infusion, followed by a 1 to 2 h rest period. 
For example, a 2.5 mg/kg SPLIT dosing schedule will administer a 1.25 mg/kg dose on 
Day 1 and a 1.25 mg/kg dose on Day 8 of each cycle.  
For the STRETCH dosing schedule, belantamab mafodotin will be administered FIRST 
(prior to Len/Dex) in the clinic on Day 1 of every alternate 28-day cycle as a 30-60 min 
infusion, followed by a 1 to 2 h rest period. A 1.9 mg/kg STRETCH dosing schedule will 
administer a 1.9 mg/kg dose on Day 1 of all alternate 28-day cycles (C1, C3, C5, C7 and 
so on).  
Starting dose in Part 1 will be 2.5 mg/kg IV for belantamab mafodotin (Dose Level 1). If 
the 2.5 mg/kg dose is not tolerated an additional, lower dose (1.9 mg/kg [Dose Level –1]) 
will be evaluated. Additionally, alternate dosing schedules will also be explored, 
including SPLIT dosing where the belantamab mafodotin dose will be split into two 
equal halves with each half dose administered on Day 1 and Day 8 of each cycle.  
Note: 2.5 mg/kg IV is the highest dose (dose level 1) that will be assessed in Arm A.  
The actual body weight in kg at baseline (assessed on C1D1 prior to dosing) will be used 
for dose calculation of belantamab mafodotin in all participants during the treatment 
period.  If the change of body weight is greater than 10%, the dose should be re-
calculated based on the actual body weight at the time of dosing.  Participants must be 
weighed prior to dosing for each cycle. 
8.1.1.2. 
Len/Dex 
Lenalidomide will be administered as 25 mg PO daily on days 1-21 of each 28-day cycle, 
in the participants with eGFR 60 mL/min/1.73 m2.  The dose of lenalidomide will be 
reduced to 10 mg daily on Days 1 to 21 in participants with eGFR of 40-60 mL/min/1.73 
m2. Lenalidomide is administered at a fixed dose level, with no adjustments needed for 
body weight or BSA [REVLIMID (lenalidomide) Prescribing Information 2019]. 
On lenalidomide and belantamab mafodotin co-administration days, lenalidomide should 
be administered as close as possible to the end of the 1-2 h rest period after 
administration of belantamab mafodotin and no later than 6 h after the end of the rest 
period after administration of belantamab mafodotin. 
Dexamethasone will be given 40 mg weekly PO or IV on Days 1, 8, 15 and 22 of each 
cycle. Dexamethasone is administered at a fixed dose of 40 or 20 mg PO or IV, with no 


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adjustments needed for body weight or BSA. For dexamethasone refer to dexamethasone 
prescribing information.  
Participants who are >75 years old, with BMI <18.5 kg/m2, the dose of dexamethasone 
can be reduced to 20 mg at the discretion of the investigator. 
In the event of tolerability issues, the dose of dexamethasone can be reduced from 40 mg 
to 20 mg; if 20 mg is not tolerated, dexamethasone may be permanently discontinued.  
On days where only lenalidomide and dexamethasone are taken at home, they should be 
taken in the morning approximately at the same time each day.  On days when 
lenalidomide PK samples will be collected, participants will be required to take their 
morning dose in the clinic. For Cycle 1, the 24 h post-dose lenalidomide PK sample must 
be collected before lenalidomide dosing on Cycle 1 Day 2. 
8.1.2. 
Belantamab Mafodotin and Bor/Dex Combination (Arm B) 21-day 
Cycle: SINGLE and SPLIT Schedules 
The schedules for dosing of belantamab and Bor/Dex on a 21-day schedule is shown in 
Figure 6 


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Figure 6 
Arm B: 21-day Dosing Schedules  
 
8.1.2.1. 
Belantamab Mafodotin 
For SINGLE day dosing schedule, belantamab mafodotin will be administered FIRST 
(prior to Bor/Dex) in the clinic as a single full dose on Day 1 of each 21-day cycle as a 
30-60 min infusion, followed by a 1 to 2 h rest period. For example, a 3.4 mg/kg 
SINGLE dosing schedule will administer a 3.4 mg/kg dose on Day 1 of each cycle, a 2.5 
mg/kg SINGLE dosing schedule will administer a 2.5 mg/kg dose on Day 1 of each 
cycle, a 1.9 mg/kg SINGLE dosing schedule will administer a 1.9 mg/kg dose on Day 1 
of each cycle.   
For SPLIT day dosing schedule, belantamab mafodotin will be administered FIRST 
(prior to Bor/Dex) in the clinic in two equal divided doses - one on Day 1 and the other 
on Day 8 of each 21-day cycle as a 30-60 min infusion, followed by a 1 to 2 h rest period. 
For example, a 2.5 mg/kg SPLIT dosing schedule will administer a 1.25 mg/kg dose on 
Day 1 and a 1.25 mg/kg dose on Day 8 of each cycle, a 3.4 mg/kg SPLIT dosing schedule 
will administer a 1.7 mg/kg dose on Day 1 and a 1.7 mg/kg dose on Day 8 of each cycle. 


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The starting dose in Part 1 will be 2.5 mg/kg IV for belantamab mafodotin (Dose Level 
1). If safety and tolerability of the starting dose is confirmed, an escalation of the dose of 
belantamab mafodotin to 3.4 mg/kg (Dose Level +1) will be performed in the next cohort 
of participants.  If the 2.5 mg/kg dose is not tolerated, or if emerging data were to indicate 
potential improved benefit/risk at reduced dose, an additional, lower dose (1.9 mg/kg 
(Dose Level –1) will be evaluated.  
Note: 3.4 mg/kg IV is the highest dose (Dose level +1) that will be assessed in Arm B   
8.1.2.2. 
Bor/Dex 
Bortezomib 1.3 mg/m2 SC or IV (depending on participants’ and institutional preference) 
will be administered on Days 1, 4, 8, and 11 of every 21-day cycle for a total of up to 8 
cycles. The administration of bortezomib will be after belantamab mafodotin 
administration, approximately after 1 h and after assuring that participant is clinically 
stable. Bortezomib doses are calculated based on the participant’s BSA (West, 2000), 
ranging from a recommended starting dose of 1.3 mg/m2 to a reduced dose of 1.0 mg/m2 
or 0.7 mg/m2 [VELCADE (bortezomib) Prescribing Information (2019)]. Formulae used 
to calculate the administered volume of bortezomib for SC or IV administration are given 
in Section 8.1.5.3. 
For participants who experience an IRR during belantamab mafodotin, bortezomib 
administration will be delayed until the IRR has resolved, and the participant is 
considered clinically stable.   
Dexamethasone will be administered at 20 mg PO or IV on Days 1, 2, 4, 5, 8, 9, 11, and 
12 of every 21-day cycle. Dexamethasone is administered at a fixed dose of 20 mg PO or 
IV, with no adjustments needed for body weight or BSA. Dexamethasone dose may be 
reduced at investigator’s discretion for participants who are older than 75 years of age, 
for participants who have BMI <18.5 kg/m2, or for participants who had previous 
unacceptable side effects associated with glucocorticoid therapy. Dexamethasone will be 
given for a total of up to 8 cycles. For dexamethasone refer to dexamethasone prescribing 
information.  
In case of lack of tolerability, dexamethasone can be reduced from 20 mg to 10 mg and if 
10 mg is not tolerated, may be permanently discontinued.  
Dexamethasone should be taken at the same time of the day and may be taken at home. 
8.1.3. 
Belantamab Mafodotin and Bor/Dex Combination (Arm B) 21-day 
Cycle: STRETCH and S/D STRETCH Dosing Schedule 
The schedule for dosing of belantamab mafodotin and Bor/Dex on a STRETCH schedule 
is shown in Figure 7. 


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Figure 7 
Arm B: STRETCH Dosing Schedule  
 
 
8.1.3.1. 
Belantamab mafodotin 
For the STRETCH dosing schedule, belantamab mafodotin will be administered FIRST 
(prior to Bor/Dex) in the clinic on Day 1 of every alternate 21-day cycles as a 30-60 min 
infusion, followed by a 1 to 2 h rest period. A 2.5 mg/kg STRETCH dosing schedule will 
administer a 2.5 mg/kg dose on Day 1 of all alternate 21-day cycles (C1, C3, C5, C7 and 
so on). A 1.9 mg/kg STRETCH dosing schedule will administer a 2.5 mg/kg dose on Day 
1 of all alternate 21-day cycles (C1, C3, C5, C7 and so on). 
For the S/D STRETCH dosing schedule, belantamab mafodotin will be administered 
FIRST (prior to Bor/Dex) in the clinic at 2.5 mg/kg as a dose on Day 1 of Cycle 1 
followed by 1.9 mg/kg step-down dose on Day 1 of all alternate 21-day cycles C3 
onwards (C3, C5, C7 and so on), as a 30-60 min infusion, followed by a 1 to 2 h rest 
period.  
8.1.3.2. 
Bor/Dex 
Bortezomib 1.3 mg/m2 SC or IV (depending on participants’ and institutional preference) 
will be administered on Days 1, 4, 8, and 11 of every 21-day cycle for a total of up to 8 
cycles. The administration of bortezomib will be after belantamab mafodotin 
administration, approximately after 1 – 2 h and after assuring that participant is clinically 
stable. Bortezomib doses are calculated based on the participant’s BSA (West, 2000), 
ranging from a recommended starting dose of 1.3 mg/m2 to a reduced dose of 1.0 mg/m2 
or  0.7 mg/m2 [VELCADE (bortezomib) Prescribing Information (2019)]. Formulae used 
to calculate the administered volume of bortezomib for SC or IV administration are given 
in Section 8.1.5.3. 


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For participants who experience an IRR during belantamab mafodotin, bortezomib 
administration will be delayed until the IRR has resolved, and the participant is 
considered clinically stable.   
Dexamethasone will be administered at 20 mg PO or IV on Days 1, 2, 4, 5, 8, 9, 11, and 
12 of every 21-day cycle. Dexamethasone is administered at a fixed dose of 20 mg PO or 
IV, with no adjustments needed for body weight or BSA. Dexamethasone dose may be 
reduced at investigator’s discretion for participants who are older than 75 years of age, 
for participants who have BMI <18.5 kg/m2, or for participants who had previous 
unacceptable side effects associated with glucocorticoid therapy. Dexamethasone will be 
given for a total of up to 8 cycles. For dexamethasone refer to dexamethasone prescribing 
information.  
In case of lack of tolerability, dexamethasone can be reduced from 20 mg to 10 mg and if 
10 mg is not tolerated, may be permanently discontinued.  
Dexamethasone should be taken at the same time of the day and may be taken at home. 
8.1.4. 
Pharmaceutical Presentation 
8.1.4.1. 
Belantamab mafodotin 
Belantamab mafodotin solution, 20 mg/mL, 1.5 mL is supplied as a sterile, preservative-
free aqueous solution of purified monoclonal ADC in type 1 untreated borosilicate clear 
glass, stoppered vials. The drug product solution appears as a clear or opalescent; 
colorless, yellow to brown liquid; essentially free from particles. The drug is supplied as 
a single-use vial. Each vial of belantamab mafodotin solution, 20 mg/mL; 1.5 mL is filled 
with 1.6 mL of solution to provide a 1.5 mL extractable volume.  
Subjects continuing treatment during PACT phase after final analysis may receive 
lyophilized study drug. Lyophilized belantamab mafodotin 100 mg/vial is supplied as a 
white to yellow powder in a single-dose vial for reconstitution and further dilution.  
8.1.4.2. 
Lenalidomide 
Lenalidomide (REVLIMID) capsules, for oral use is available in 2.5 mg, 5 mg, 10 mg, 
15 mg, 20 mg and 25 mg capsules for oral administration. For details of pharmaceutical 
presentation or prescribing information refer to the local prescribing information for 
lenalidomide.  
8.1.4.3. 
Bortezomib 
Bortezomib (VELCADE) for Injection is supplied as individually-cartoned 10 mL vials 
containing 3.5 mg of bortezomib as a white to off-white cake or powder.  Retain in 
original package to protect from light. For details of pharmaceutical presentation or 
prescribing information refer to the local prescribing information for bortezomib.  


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8.1.4.4. 
Dexamethasone 
Dexamethasone is available in a tablet formulation for oral administration and as 
Dexamethasone Sodium Phosphate Injection (USP), a sterile solution of dexamethasone 
sodium phosphate in water for injection for intravenous (IV) use. For details of 
pharmaceutical presentation or prescribing information refer to the local prescribing 
information for dexamethasone.


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Table 19 
Description and Identity of Study Treatments 
Study Treatment Name 
Belantamab 
mafodotin 
Arm A and Arm B 
Arm A Standard of Care (28-Day Cycle) 
Arm B Standard of Care (21-Day Cycle) 
Lenalidomide 
Dexamethasone 
Bortezomib 
Dexamethasone 
Dosage Formulation 
20 mg/mL, 1.5 mL vial  
or 
Lyophilized powder, 
100 mg/vial in single-
use vial for 
reconstitution (Subjects 
continuing treatment in 
PACT phase after final 
analysis may receive 
lyophilized study drug) 
Capsules, for oral use 
Tablets for oral 
administration / 
Injection for IV use 
Solution for injection, 
for subcutaneous (2.5 
mg/mL) or intravenous 
(1 mg/mL) use 
Tablet for oral 
administration / 
Injection for IV use 
Route of Administration  
IV Infusion (See SRM 
for details) 
Oral 
Oral or IV 
IV as a 3 to 5 second 
bolus Infusion or SC 
Oral or IV 
Dosing Instructions 
30-60 min IV infusion  
Days 1 to 21 of each    
28-day cycle  
Days 1, 8, 15, and 22 of 
each 28-day cycle  
Days 1, 4, 8, and 11 of 
every 21-day cycle 
Days 1, 2, 4, 5, 8, 9, 11, 
and 12 of every 21-day 
cycle 
Packaging and Labelling 
Open-label 
Open-label 
Open-label 
Open-label 
Open-label 


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Study Treatment Name 
Belantamab 
mafodotin 
Arm A and Arm B 
Arm A Standard of Care (28-Day Cycle) 
Arm B Standard of Care (21-Day Cycle) 
Lenalidomide 
Dexamethasone 
Bortezomib 
Dexamethasone 
Manufacturer/ Source of 
Procurement 
GlaxoSmithKline/Baxter Celgene Corporation 
(US & Europe) 
Refer to SRM for 
country-specific details 
Refer to SRM for 
country-specific details 
Millennium 
Pharmaceuticals, Inc. 
(US) 
Janssen Pharmaceutica 
(Europe) 
Refer to SRM for 
country-specific details 
Refer to SRM for 
country-specific details    
 


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8.1.5. 
Preparation of Doses 
8.1.5.1. 
Belantamab mafodotin 
Belantamab mafodotin will be administered intravenously over 30 min to 1 h. The 
maximum dose to be administered to participants in this trial is 3.4 mg/kg. Dilute 
belantamab mafodotin solution in normal 0.9% saline to the appropriate concentration for 
the dose. For lyophilized powder, reconstitute belantamab mafodotin lyophilized powder 
100 mg/vial 2.0mL of water for injection (WFI); dilute with saline to the appropriate 
concentration for the dose before use. 
Refer to the SRM for more details on preparation and handling, and administration 
instructions for belantamab mafodotin. 
8.1.5.2. 
Lenalidomide 
Lenalidomide is administered at a fixed dose level of 25 or 10 mg PO, depending upon 
renal function. Refer to the SRM for more details on preparation, handling, and 
administration instructions for lenalidomide. Dose modifications may be required for 
safety; see Table 23 for further information. 
8.1.5.3. 
Bortezomib 
Bortezomib dosing is based on the participant’s body surface area (BSA; West, 2000). 
The reconstituted concentration of bortezomib for subcutaneous administration 
(2.5 mg/mL) is greater than the reconstituted concentration of bortezomib for intravenous 
administration (1 mg/mL). Because each route of administration has a different 
reconstituted concentration, caution should be used when calculating the volume to be 
administered. Dose modifications may be required for safety, see Table 24 for further 
information. 
After determining the participant’s BSA in m2, use the following equations to calculate 
the total volume (mL) of reconstituted bortezomib to be administered: 
For Intravenous Administration (1 mg/mL concentration) 
[bortezomib dose (mg/m2) × participant BSA (m2)]  [1 mg⁄mL] = Total bortezomib 
volume (mL) to be administered 
For Subcutaneous Administration (2.5 mg/mL concentration) 
[bortezomib dose (mg/m2) × participant BSA (m2)]  [2.5 mg⁄mL] = Total bortezomib 
volume (mL) to be administered 
Refer to the SRM for more details on preparation, handling, and administration 
instructions for bortezomib. 


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8.1.5.4. 
Dexamethasone 
Dexamethasone is administered at a fixed dose level of 40 mg or 20 mg (PO or IV) at the 
discretion of the investigator, and is not adjusted for weight or BSA. Refer to the SRM 
for more details on preparation and handling, and administration instructions for 
dexamethasone. 
8.1.6. 
Treatment Duration 
8.1.6.1. 
Arm A 
For participants assigned to Arm A (belantamab mafodotin in combination with Len/Dex, 
28-day cycle), participants may continue combination treatment until the occurrence of 
PD, intolerable AEs, consent withdrawal, death, or end of study. 
8.1.6.2. 
Arm B 
For participants assigned to Arm B (belantamab mafodotin in combination with Bor/Dex, 
21-day cycle), participants may continue combination treatment for a total of up to 8 
cycles, as per prescribing information for bortezomib for the treatment of RRMM. 
Participants completing 8 cycles of combination therapy will continue treatment with 
belantamab mafodotin as monotherapy until PD, intolerable AEs, consent withdrawal, 
death, or end of study.  
8.1.6.3. 
Lack of tolerability in Arm A or B 
In case a participant meets stopping criteria for Len/Dex or Bor/Dex treatment and cannot 
continue on Len/Dex or Bor/Dex treatment due to related safety/tolerability issues, the 
participant may continue on study with belantamab mafodotin monotherapy. In case the 
participant meets stopping criteria for belantamab mafodotin, the participant will 
discontinue all treatment but will continue to be monitored as described in the SoA tables 
for follow-up activities. Cross over between arms is not allowed. 
8.2. 
Dose Modification 
After the completion of Cycle 1, dose modifications for all study drugs are allowed 
(within restrictions) to manage tolerability or adverse events. 
8.2.1. 
Dose Modification After Cycle 1 
In both Part 1 and Part 2 of the study after Cycle 1, and dose modifications may be made 
for individual participants, based on safety findings. Dose interruptions and reductions 
are permitted throughout the study per guidance below.    
The dose allowed for belantamab mafodotin may be reduced twice by 25% of the 
originally assigned dose. The rule of 25% dose reduction always refers to the originally 
assigned dose. If the participant is unable to tolerate at least a full dose of belantamab 
mafodotin 1.9 mg/kg (including SPLIT dose of 0.95 mg/kg on Day 1 and Day 8), they 
will be withdrawn from the trial due to unacceptable toxicity (Table 21).  


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For the S/D STRETCH dosing schedules, belantamab mafodotin will be administered at 
2.5 mg/kg on D1 of Cycle 1 followed by 1.9 mg/kg dose in all subsequent alternate 
planned cycles starting at Cycle 3 Day 1 throughout the rest of treatment. As 1.9 mg/kg is 
the lowest full dose evaluated in this study, no dose reductions for belantamab mafodotin, 
except for dose delays and interruptions, will be allowed. If the participant is unable to 
tolerate the dose of belantamab mafodotin at 1.9 mg/kg, they will be withdrawn from the 
trial due to unacceptable toxicity (Table 21).  
In Arm A, for the 1.9 mg/kg STRETCH dosing schedule, if a planned dose of belantamab 
mafodotin was held/missed due to any reason, the next dose can be administered at Day 1 
of the next planned 28-day cycle, as long as the interval between 2 consecutive doses is at 
least 56 (3) days.  
In Arm B, for the S/D STRETCH, 2.5 mg/kg STRETCH and 1.9 mg/kg STRETCH 
dosing schedules, if a planned dose of belantamab mafodotin was held/missed due to any 
reason, the next dose can be administered at Day 1 of the next planned 21-day cycle, as 
long as the interval between 2 consecutive doses is at least 42 (3) days.  
• 
Detailed guidance for belantamab mafodotin dose reductions and delays is shown in 
Table 20, Table 21, and Table 22.   
• 
Detailed guidance for lenalidomide dose reductions and delays is shown in Table 23. 
• 
Detailed guidance for bortezomib dose reductions and delays is shown in Table 24. 
• 
Detailed guidance for dexamethasone dose reductions and delays is shown in Table 
25 (Arm A) and Table 26 (Arm B). 
Dosing delays also are permitted for medical/surgical events or for logistical reasons not 
related to study therapy (e.g., COVID-19 related restrictions, ophthalmology services 
unavailable, elective surgery, unrelated medical events, participant vacation, and/or 
public holidays, but not for a participants’ decision to delay treatment). The reason for 
any dose delay must be documented in the participant's eCRF and clinic records. 
Refer to the SRM for more details on dose modification scenarios. 
 


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Table 20 
Recommendations for Dose Reduction of Belantamab Mafodotin 
 
 
SINGLE Dosing 
SPLIT Dosing 
STRETCH Dosing 
Treatment 
Arm 
Arm A and Arm B 
Arm B only 
Arm A and Arm B 
Arm Aa and Arm 
B 
Arm B only 
Assigned 
Dose 
1.9 mg/kg 
on Day 1  
2.5 mg/kg on 
Day 1 
3.4 mg/kg on 
Day 1 
2.5 mg/kg 
SPLIT into 1.25 
mg/kg on Day 1 
and Day 8 
3.4 mg/kg SPLIT 
into 1.7 mg/kg on 
Day 1 and Day 8 
1.9 mg/kg 
STRETCH 
2.5 mg/kg 
STRETCH 
S/D STRETCH 
Dose upon 
First 25% 
Dose 
Reduction 
from 
Assigned 
Dose 
No dose 
reduction 
allowed 
1.9 mg/kg (no 
dose 
reductions 
below a full 
dose of 1.9 
mg/kg 
allowed) 
2.5 mg/kg 
1.9 mg/kg 
SPLIT into 0.95 
mg/kg on Day 1 
and Day 8 (no 
dose reductions 
below a full 
dose of 1.9 
mg/kg allowed) 
2.5 mg/kg SPLIT 
into 1.25 mg/kg 
on Day 1 and 
Day 8 
No dose reduction 
allowed 
1.9 mg/kg 
STRETCH (no 
dose reductions 
below a full dose 
of 1.9 mg/kg 
allowed) 
No dose 
reduction below 
1.9 mg/kg 
allowed 
Dose upon 
Second 25% 
Dose 
Reduction 
from 
Assigned 
Dose 
No dose 
reduction 
allowed 
No dose 
reduction 
allowed 
1.9 mg/kg (no 
dose 
reductions 
below a full 
dose of 1.9 
mg/kg 
allowed) 
No dose 
reduction 
allowed 
1.9 mg/kg SPLIT 
into 0.95 mg/kg 
on Day 1 and 
Day 8 (no dose 
reductions below 
a full dose of 1.9 
mg/kg allowed) 
No dose reduction 
allowed 
No dose 
reduction 
allowed 
No dose 
reduction 
allowed 
a. The 1.9 mg/kg STRETCH dosing schedule for Arm A may be evaluated if emerging data suggests that this schedule may further 
optimize the tolerability or offers an improved benefit/risk profile. 
 


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Table 21 
Dose Modification Guidelines for Adverse Events Associated with Belantamab Mafodotin (Arm A and B) 
Toxicity 
Grade/Symptoms 
Recommendations  
Serum creatinine elevation which cannot be 
explained by concomitant sepsis, TLS, other 
severe infection with fever or dehydration 
 
If absolute serum 
creatinine increase 
from baseline of 
>0.5 mg/dL  
Repeat within 48 h 
• If confirmed: withhold therapy, institute treatment and monitoring as clinically 
indicated, and follow for resolution. 
• Discuss any further dosing with Medical Monitora. 
Serum creatinine Grade >3 
>3.0 mg/dL from 
baseline 
or 
3.0-6.0 × ULN 
• Provide appropriate medical treatment 
• Permanently discontinue treatment with belantamab mafodotin 
Spot urine (creatinine / albumin ratios) 
>2000 mg/g 
(224 mg/mmol) 
• Re-test (at least 7 days apart) 
• If not confirmed, continue belantamab mafodotin at 100% dose 
• If confirmed on re-test and no clear evidence of disease progressiona 
• Interrupt treatment with belantamab mafodotin 
• Repeat testing within 4 weeks 
• If spot urine ≤ 2000 mg/g (224 mg/mmol) may restart belantamab 
mafodotin with 25% dose reduction b.  
• 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 resolution. 
Thrombocytopenia (on days of dosing)  
 
Graded according to NCI-CTCAE criteria 
Grade 3 
SINGLE and 2.5 mg/kg STRETCH Dosing: 
• 
No bleeding: continue treatment with 25% dose reduction b. Consider reverting to 
previous dose once thrombocytopenia recovered to Grade 2, or less.  
• 
With bleeding: withhold dose. Treatment with a 25% dose reductiona may continue 
after thrombocytopenia has recovered to Grade 2 or less.  
• 
Consider additional supportive treatment (e.g., transfusion), as clinically indicated 
and per local practice. 
 
 


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Toxicity 
Grade/Symptoms 
Recommendations  
SPLIT Dosing: 
• 
If noted on Day 1 of any cycle, follow guidance outlined above for SINGLE Day 
dosing for “No bleeding” vs “With bleeding” scenarios as appropriate. 
• 
If noted on Day 8 of any cycle; and participant has received belantamab mafodotin 
on Day 1: 
o No bleeding: continue belantamab mafodotin Day 8 dosing with a 25% 
dose reductionb. Consider reverting to previous dose once 
thrombocytopenia recovers to Grade 2, or less.  
o If the dose is unable to be administered on Day 8 of the cycle, it can be 
withheld and administered at any time, up to, and including Day 15 of the 
same cycle, and once the investigator determines the participant is 
clinically fit to receive the dose. 
o If belantamab mafodotin is withheld on Day 8 through Day 15 due to 
clinical reasons, then belantamab mafodotin will not be administered until 
Day 1 of the next planned 28-day cycle for Arm A or Day 1 of the next 
planned 21-day cycle for Arm B. 
o With bleeding: withhold belantamab mafodotin and provide supportive care 
to stop the bleeding.   
o Continue treatment after recovery with the 25% dose reduction b.   
o If the dose is unable to be administered on Day 8 of the cycle, it can be 
withheld and administered at any time, up to, and including Day 15 of the 
same cycle, and once the investigator determines the participant is 
clinically fit to receive the dose. 
o If belantamab mafodotin is withheld on Day 8 and up to Day 15 due to 
clinical reasons, then belantamab mafodotin will not be administered until 
Day 1 of the next planned 28-day cycle for Arm A or Day 1 of the next 
planned 21-day cycle for Arm B.  
 
S/D STRETCH and 1.9 mg/kg STRETCH Dosing: 
• 
No bleeding: withhold dose.  Treatment at 1.9 mg/kg dose may continue after 
thrombocytopenia has recovered to Grade 2 or less. 


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Toxicity 
Grade/Symptoms 
Recommendations  
• 
With bleeding: withhold dose. Treatment at 1.9 mg/kg dose may continue after 
thrombocytopenia has recovered to Grade 2 or less. 
• 
Consider additional supportive treatment (e.g., transfusion), as clinically indicated 
and per local practice. 
Grade 4 
• 
Withhold the belantamab mafodotin dose. Consider restarting with 25% dose 
reductiona if thrombocytopenia recovers to Grade 3 and only if there is no active 
bleeding at time of treatment restart. 
If thrombocytopenia is considered disease-related, and is not accompanied by 
concurrent bleeding, and which recovers following transfusion to >25 x109/L belantamab 
mafodotin treatment with 25-50% dose reductiona may be considered following 
discussion with the GSK Medical Monitor. 
Febrile neutropenia 
 
Graded according to NCI-CTCAE criteria 
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).b 
Upon recovery, consider a 25% dose reduction a of belantamab mafodotin, if 
neutropenia was drug-related.  
Neutrophil Count Decreased (Neutropenia) 
 
Graded according to NCI-CTCAE criteria 
Grade 3-4 
• 
Defined as ANC <1.0x109/L 
SINGLE, STRETCH and S/D STRETCH Dosing: 
• 
If noted on Day 1 of any cycle, withhold belantamab mafodotin. Repeat hematology 
(CBC) as clinically indicated.  
• 
Resume belantamab mafodotin at pre-held dose once neutropenia recovers to 
Grade ≤ 2 (ANC ≥ 1.0x109/L) on Day 1 of the subsequent cycle.  
• 
Consider prophylactic antibiotics, per physician discretion and local institutional 
guidance, in participants with Grade 3-4 neutropenia (ANC <1.0x109/L), even if 
afebrile. Consider growth factorsb. 
SPLIT Dosing 
• 
If noted on Day 1 of any cycle, follow guidelines as outlined above for single Day 1 
dosing 
• 
If noted on Day 8 of any cycle, and participant has received belantamab mafodotin 
on Day 1, then continue belantamab mafodotin Day 8 dosing unless the investigator 


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Toxicity 
Grade/Symptoms 
Recommendations  
determines that the participant is clinically unfit to receive the dose (e.g., febrile 
neutropenia).  
• 
If the dose is unable to be administered on Day 8 of the cycle, it can be withheld and 
administered at any time, up to, and including on Day 15 of the same cycle, and 
once the investigator determines the participant is clinically fit to receive the dose.  
• 
If belantamab mafodotin is withheld on Day 8 up to Day 15 due to clinical reasons, 
then belantamab mafodotin will not be administered until Day 1 of the next planned 
28-day cycle for Arm A or Day 1 of the next planned 21-day cycle for Arm B. 
For a subsequent 
drop in ANC to 
<1.0 × 109 /L 
• 
Consider 25% dose reduction b of belantamab mafodotin, if it was drug-related. 
Infusion Reaction 
Graded according to NCI-
CTCAE criteria 
Note: If symptoms resolve within 1 h of stopping drug infusion, the infusion may be restarted at 50% of the 
original infusion rate (e.g., from 100 mL/h to 50 mL/h).  Otherwise dosing will be held until symptoms resolve 
and the participant should be premedicated at the next scheduled dose  
Grade 2 
• 
Stop infusion, provide medical treatment and continue at slower infusion rate after 
resolution to Grade 0-1 
Grade 3 
• 
Further treatment with belantamab mafodotin needs to be discussed with Medical 
Monitor. Continuation only allowed after recovery to  Grade 1 and with 
premedication, and extension of infusion time to 2-4 h. Any future infusion needs to 
be premedicated. 
Grade 4 
• 
Permanently discontinue 
Pneumonitis 
Graded according to NCI-CTCAE criteria 
Grade 1 
Withhold dose and follow recommendations below:  
• 
Obtain high resolution chest CT if possible.  
• 
CT scan (high-resolution with lung windows) recommended  
• 
Clinical evaluation and laboratory work-up for infection  
• 
Monitoring of oxygenation via pulse-oximetry recommended  
• 
Consultation with pulmonologist recommended  
• 
If resolved: Retreatment at the full dose is possible  


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Toxicity 
Grade/Symptoms 
Recommendations  
 
Grade 2 
Withhold treatment with belantamab mafodotin  
Follow recommendations below:  
• Obtain high resolution chest CT if possible.  
• CT scan (high-resolution with lung windows)  
• Clinical evaluation and laboratory work-up for infection  
• Consult pulmonologist 
• Pulmonary function tests (PFT) – if abnormal, repeat every 8 weeks until back to 
baseline  
• Bronchoscopy with biopsy and/or bronchoalveolar lavage (BAL) recommended  
• Symptomatic therapy including corticosteroids if clinically indicated  
 
If resolved: Restart treatment with 50% dose reduction b.  
Grade 3-4 
Permanently discontinue treatment with belantamab mafodotin and follow 
recommendations below.  
• 
Obtain CT scan (high-resolution with lung windows) 
• 
Clinical evaluation and laboratory work-up for infection  
• 
Consult pulmonologist  
• 
PFT – if abnormal, repeat every 8 weeks until back to baseline bronchoscopy with 
biopsy and/or BAL if possible.  
• 
Symptomatic therapy including corticosteroids as clinically indicated 
a. 
Medical monitor may consult GSK’s Nephrology safety panel regarding treatment continuation.  
b. 
Dose reduction strategy: see Table 20. 
 
 
 


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Table 22 
Dose Modification Guidelines for Belantamab Mafodotin Treatment-Related Corneal Events 
Grade 1 per GSK Scalea 
Grade 2 per GSK Scalea 
Grade 3 per GSK Scalea 
Grade 4 per GSK Scalea 
Belantamab Mafodotin 
Dosing Actions 
Continue treatment with current 
dose of belantamab mafodotin. 
If either ophthalmic exam 
findings or visual acuity findings 
are Grade 1, continue dosing 
with belantamab mafodotin at 
current dose. 
If visual acuity and exam 
findings are both Grade2, 
HOLD belantamab mafodotin. 
• 
Upon improvement of 
either visual acuity or 
ophthalmic exam findings 
to Grade 1 or baseline, 
resume with current dose 
Hold belantamab mafodotin. 
• 
Upon improvement of 
either visual acuity or 
ophthalmic exam findings 
to Grade 1 or baseline, 
resume with 25% dose 
reduction* 
(* for participants receiving 
1.9 mg/kg dose continue at 
1.9 mg/kg)  
In case of recurring ≥Grade 3 
events, consult GSK Medical 
monitor 
Stop treatment with belantamab 
mafodotin. 
Additional topical treatment may 
be prescribed, as recommended 
by ophthalmologist* 
Treatment re-start may be 
possible after discussion and 
agreement between the treating 
qualified eye care specialist, 
treating physician, the GSK 
Medical Monitor and possibly a 
GSK ophthalmologist 
Corneal Management 
Care Regardless of 
Grade 
Preservative-free artificial tears: 
• 
Increase to 1 drop as frequently as every 2 h, as needed 
Cooling Eye Masks: 
At the start of each infusion, participants may apply cooling eye masks to their eyes for approximately 1 h or as long as tolerated. 
Steroid Eye Drops: 
Corticosteroid eye drops are not required as prophylaxis but can be used therapeutically if clinically indicated per discretion of an eye care 
specialist. Allow at least 5-10 minutes between administration of artificial tears and steroid eye drops (if administered). 
a.  See Appendix 8 for GSK Scale for belantamab mafodotin Corneal Events 


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Table 23 
Dose Modification Guidelines for Hematologic and Other Toxicities Associated with Lenalidomide Plus 
Dexamethasone (Arm A) 
Toxicity 
Grade/Symptoms 
Recommendations 
Thrombocytopeniaa 
Platelets fall to <30 × 109 /L 
• 
Interrupt lenalidomide, follow by weekly hematology assessment 
Platelets return to ≥30 × 109 /L 
• 
Resume lenalidomide at next lower dose. Do not dose below 2.5 mg daily 
For each subsequent drop in platelets 
to <30 × 109 /L 
• 
Interrupt lenalidomide treatment. Do not dose below 5 mg daily for Days 1 to 21 of 
28-day cycle 
Platelets return to ≥30 × 109 /L 
• 
Resume lenalidomide at 5 mg daily for Days 1 to 21 of 28-day cycle. Do not dose 
below 5 mg daily for Days 1 to 21 of 28-day cycle 
Neutropeniab 
Absolute Neutrophil Counts 
(ANC) 
ANC fall to <1.0 × 109 /L 
• 
Interrupt lenalidomide, hematology (CBC) at least once a week  
• 
Consider prophylactic antimicrobials per physician discretion and institutional 
guidelines  
• 
Consider additional supportive treatment, per local practice (e.g., growth factors) 
• 
Immediate hospitalization for febrile neutropenia is required 
When ANC returns to ≥ 1.0 × 109 /L 
• 
Resume lenalidomide at next lower dose, continuously for Days 1-21 of repeated 
28-day cycle 
For a subsequent drop in ANC to 
<1.0 × 109 /L 
• 
Interrupt lenalidomide treatment.  
When ANC returns to ≥1.0 × 109 /L 
• 
Resume lenalidomide at next lower dose daily for Days 1 to 21 of 28-day cycle. Do 
not dose below 5 mg daily for Days 1 to 21 of 28-day cycle 
Cutaneous Reactions 
Grade 2-3 
• 
Consider dose interruption or discontinue lenalidomide 
Grade 4 
• 
Permanently discontinue lenalidomide  
Hypersensitivity 
Angioedema and anaphylaxis 
• 
Permanently discontinue lenalidomide 


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Toxicity 
Grade/Symptoms 
Recommendations 
For other non-hematological 
toxicities judged to be related 
to lenalidomide  
Grade 3 to 4 
• 
Hold lenalidomide treatment and restart at the physician’s discretion at next lower 
dose level when toxicity has resolved to Grade 2 
a. 
Note that in the REVLIMID (lenalidomide) PI, platelet counts and neutrophil counts are presented as 30,000/mcL; those values have been converted to 30×109/L to maintain 
consistency with protocol laboratory conventions. 
b. 
Note that in the REVLIMID (lenalidomide) PI, platelet counts and neutrophil counts are presented as 1,000/mcL; those values have been converted to 1.0×109/L to maintain 
consistency with protocol laboratory conventions 
Data Source: REVLIMID (lenalidomide) Approved Labelling. 
Table 24 
Dose Modification Guidelines for Hematologic and Other Toxicities Associated with Bortezomib Plus 
Dexamethasone (Arm B) 
Toxicity 
Gradea/Symptoms 
Recommendations 
Hematological toxicity 
Graded according to NCI-
CTCAE criteria 
Grade 4 
• 
Withhold bortezomib therapy until symptoms of toxicity have resolved.  
• 
Bortezomib may be reinitiated with 1 dose level reduction (from 1.3 mg/m2 to 1 mg/m2, 
or from 1 mg/m2 to 0.7 mg/m2) 
Non-hematological toxicities 
(excluding peripheral 
neuropathy)c 
Grade ≥ 3 
• 
Withhold bortezomib therapy until symptoms of toxicity have resolved. Then, 
bortezomib may be reinitiated with 1 dose level reduction (from 1.3 mg/m2 to 1 mg/m2, 
or from 1 mg/m2 to 0.7 mg/m2).  
• 
For bortezomib-related neuropathic pain and/or peripheral neuropathy, hold or modify 
bortezomib as outlined in the bortezomib Approved Labelling. 
Peripheral Neuropathyb 
 
 
Grade 1 (asymptomatic; loss of 
deep tendon reflexes or 
paresthesia) without pain or loss of 
function 
• 
No action 
Grade 1 with pain, or  
Grade 2 (moderate symptoms; 
limiting instrumental Activities of 
Daily Living [ADLc]) 
• 
Reduce bortezomib to 1 mg/m2 


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Toxicity 
Gradea/Symptoms 
Recommendations 
Grade 2 with pain or  
Grade 3 (severe symptoms; 
limiting self care ADLd) 
• 
Withhold bortezomib therapy until toxicity resolves. When toxicity resolves, reinitiate 
with a reduced dose of bortezomib at 0.7 mg/m2 once per week. 
Grade 4 (life threatening 
consequences; urgent intervention 
indicated) 
• 
Discontinue bortezomib. 
a. 
Criteria and Recommendations from bortezomib Approved Labelling. 
b. 
Criteria and Recommendations for Peripheral Neuropathy from bortezomib Approved Labelling. 
c. 
Instrumental ADL: refers to preparing meals, shopping for groceries or clothes, using telephone, managing money etc. 
d. 
Self-care ADL: refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. 
Data Source: bortezomib Approved Labelling. 
 
 


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8.2.2. 
Dose Modification Guidelines for Dexamethasone 
For participants who are intolerant to full dose of dexamethasone, the dose of dexamethasone can be reduced as per guidance below: 
Table 25 
Dose Modification Guidelines for Toxicities Related to Dexamethasone in Arm A 
Toxicity 
Recommendations 
For participants who are >75 with BMI 
<18.5 kg/m2 
Reduce the dose of dexamethasone by 50% (i.e. from 40 mg to 20 mg) at the discretion of the investigator. 
Lack of tolerance or significant toxicities 
related to dexamethasone 
Reduce dexamethasone dose by 50% (i.e. from 40 mg to 20 mg). If 20 mg is not tolerated, the dexamethasone dose 
can be further reduced, or permanently discontinued. 
  
Table 26 
Dose Modification Guidelines for Toxicities Related to Dexamethasone in Arm B 
Toxicity 
Recommendations 
For participants who are >75 years, with 
BMI <18.5 kg/m2 
Reduce the dose of dexamethasone by 50% (i.e. from 20 mg to 10 mg) at the discretion of the investigator. 
Lack of tolerance or significant toxicities 
related to dexamethasone 
Reduce dexamethasone dose by 50% (i.e. from 20 mg to 10 mg). If 10 mg is not tolerated, the dexamethasone dose 
can be further reduced or permanently discontinued. 
 


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8.3. 
Method of Treatment Assignment 
A unique participant number will be assigned to all participants who sign the ICF and are 
screened in the study. 
Participants, who satisfy the Inclusion and Exclusion criteria for entry, will be assigned to 
either Arm A or Arm B at the discretion of the investigator, until the maximum planned 
number of participants is obtained in each treatment group.   
Crossover between arms is not permitted in this study. 
Study treatment will be dispensed at the study visits summarized in the Schedule of 
Activities (Section 3). Returned study treatments (lenalidomide, bortezomib, or 
dexamethasone) should not be re-dispensed to the participants. 
8.4. 
Blinding 
This is an open-label study; therefore, no blinding of treatment identity is needed for 
either Arm A or Arm B.   
8.5. 
Preparation/Handling/Storage/Accountability 
• The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study treatment received and any discrepancies 
are reported and resolved before use of the study treatment. 
• Only participants enrolled in the study may receive study treatment and only 
authorized site staff may supply or administer study treatment. All study treatments 
must be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labelled storage conditions with access 
limited to the investigator and authorized site staff. 
• The investigator, designee, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance 
(i.e., receipt, reconciliation, and final disposition records). 
• Further guidance and information for the final disposition of unused study treatment 
are provided in the SRM.  
• 
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. 
• 
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 
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8.6. 
Treatment Compliance 
When participants have parenteral study treatments (belantamab mafodotin or bortezomib 
or dexamethasone) administered at the site, they will receive study treatment in the clinic 
under supervision of the investigator or designee. The date and time of each dose 
administered in the clinic will be recorded in the participant’s CRF and source 
documents. The dose of study treatment and study participant identification will be 
confirmed at the time of dosing by a member of the study site staff other than the person 
administering the study treatment. 
When participants self-administer oral study treatment(s) at home, dosing with Len/Dex 
(Arm A) or with dexamethasone (Arm B) will be recorded in the Participant’s Study 
Diary. The entries in the Diary will be assessed through querying the participant during 
the site visits and documented in the source documents and CRF. A record of the number 
of doses dispensed to and taken by each participant must be maintained and reconciled 
with study treatment and compliance records. Treatment start and stop dates, including 
dates for treatment delays and/or dose reductions will also be recorded in the CRF. 
In addition, a complete list of all prior anti-cancer therapies will be recorded in the eCRF. 
8.7. 
Concomitant Therapy 
Participants will be instructed to inform the investigator prior to starting any new 
medications from the time of first dose of study treatment until the End of the Study 
Treatment Visit. Any concomitant medication (including over-the-counter or prescription 
medicines, vitamins, and/or herbal supplements) that the participant is receiving at the 
time of enrollment or receives during the study must be recorded along with: 
• 
reason for use 
• 
dates of administration including start and end dates 
• 
dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant therapy. 
8.7.1. 
Permitted Concomitant Medications and Therapies 
Participants should receive full supportive care during the study, including transfusions, 
growth factors, and treatment with antibiotics, anti-emetics, antidiarrheals, and 
analgesics, as appropriate.  
Concomitant therapy with bisphosphonates is allowed.  
Concomitant prophylactic treatment for tumor lysis syndrome (according to local 
standards) in participants with high tumor load should be considered. 
Participants may receive local irradiation for pain control or stability control. 


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Several permitted concomitant medications may need special monitoring if used. Please 
refer to the SRM for details. 
8.7.2. 
Prohibited Concomitant Medications and Therapies 
Chronic treatment with oral steroids other than part of the study treatment is prohibited 
while the participant is on study with the exception of low dose prednisolone (<10 mg/d) 
as substitution in participants with adrenal insufficiency.  
A short course (up to 7 days) of steroids is allowed to manage rash, treatment-induced 
diarrhea, or other acute complications. Steroids may be used to treat infusion related 
reactions. Inhaled steroids are allowed. 
Plasmapheresis is prohibited from 7 days prior to first dose of study drug through the end 
of study treatment. 
Administration of live or live-attenuated vaccines are contraindicated 30 days prior to the 
first dose of study treatment and while receiving study treatment. Use of live or live-
attenuated vaccines is further contraindicated for at least 70 days following the last dose 
of belantamab mafodotin.  Killed or inactivated vaccines may be administered; however, 
the response to such vaccines cannot be predicted. 
Elimination pathways for belantamab mafodotin and cys-mcMMAF have not been 
characterized in humans; however, cys-mcMMAF was shown to be a substrate of P-gp 
and OATP transporters and to be a poor substrate of CYP enzymes in vitro.  Caution 
should be exercised when belantamab mafodotin is combined with strong inhibitors of P-
gp, and strong inhibitors of OATP should be avoided unless considered medically 
necessary. 
A list of Prohibited Concomitant Medications is provided in SRM, based on known 
interactions or characteristics of each component of the Study Treatment.  
8.7.3. 
Prohibited Devices 
Contact lenses are prohibited while the participant is on study treatment.  
8.8. 
 Treatment After the End of the Study 
Study participants that continue to benefit from study intervention beyond the DCO date 
will continue to have access to study intervention until the EOS as defined in Section 8.9. 
There is no planned intervention following the EOS. 
The Investigator is responsible for ensuring that consideration has been given to the post-
study care of the participant’s medical condition. 
Refer to End of Treatment & Follow-Up Assessments for participants who are to be 
followed for disease progression and/or survival after they permanently discontinue from 
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8.9. 
Continued Access to Study Intervention after Final Data cut  
Participants receiving belantamab mafodotin monotherapy or in combination with either 
Len/Dex (Arm A) or Bor/Dex (Arm B) at the time of the final analysis data cut-off date,  
may continue to receive belantamab mafodotin monotherapy or in combination with 
either Len/Dex (Arm A) or Bor/Dex (Arm B), if in the opinion of their treating physician, 
they are continuing to derive clinical benefit from continued treatment. In case the 
participant meets stopping criteria for belantamab mafodotin, the participant will 
discontinue all treatment and will continue to be monitored as per standard of care at the 
participant’s particular study site. Study treatment will continue until a study 
discontinuation (see Protocol Section 9.3) as assessed by the investigator has been met.  
Participants who continue study treatment in the PACT phase will be cared for in 
accordance with local standard clinical practice Investigators must report all SAEs, AEs 
leading to treatment discontinuation, overdose and pregnancy cases until 70 days after 
receipt of their last dose of study treatment in accordance with Section 10.2.4 (Reporting 
of Serious Adverse Events). Pre-specified ocular data (refer to the SRM) will be reported 
for up to 12 months from the end of PACT treatment or until resolution (to Grade 1 or 
baseline), whichever comes first.  
Post final analysis data cut-off, reporting and follow up of SAEs, AEs leading to 
treatment discontinuation, overdose and pregnancy cases and pre-specified ocular data 
will be done via paper forms (see SRM for details).  
For dispensing of study treatment and drug accountability in the PACT phase please refer 
to the SRM.  
9. 
DISCONTINUATION CRITERIA 
9.1. 
Discontinuation of Study Treatment 
All participants who discontinue from study treatment will have safety assessments at the 
time of discontinuation and during EOT Follow-up as specified in Table 10. Participants 
will receive study treatment until disease progression, death or unacceptable toxicity.  
Study treatment may be permanently discontinued for any of the following reasons: 
• 
Participant has met any of the protocol defined safety stopping criteria (Section 
9.2) 
• 
Deviation(s) from the protocol 
• 
Request of the participant or proxy (withdrawal of consent by participant or 
proxy) 
• 
Investigator’s discretion 
• 
Pregnancy 
• 
Participant is lost to Follow-up  
• 
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If the participant voluntarily discontinues from treatment due to toxicity, ‘adverse event 
(AE)’ will be recorded as the primary reason for permanently discontinuation on the 
electronic case report form (eCRF).    
Once a participant has permanently discontinued from study treatment, the participant 
will not be allowed to re-start taking study treatment. 
9.1.1. 
Discontinuation of Individual Components of Combination Study 
Treatment 
The primary reason study treatment was permanently discontinued must be documented 
in the participant’s medical records and eCRF. 
• 
At the discretion of the investigator and in consultation with the Medical Monitor, 
participants assigned to Arm A and meeting Stopping Criteria for lenalidomide plus 
dexamethasone may continue to receive belantamab mafodotin monotherapy on the 
approved schedule until PD, unacceptable toxicity, or death occurs. The primary 
reason each study treatment was discontinued must be documented in the medical 
record and on the eCRF.   
• 
At the discretion of the investigator and in consultation with the Medical Monitor, 
participants assigned to Arm B and meeting Stopping Criteria for bortezomib plus 
dexamethasone prior to completing 8 cycles, may still continue to receive 
belantamab mafodotin monotherapy until PD, unacceptable toxicity, or death occurs.  
The primary reason each study treatment was discontinued must be documented in 
the medical record and on the eCRF.  
The reason for discontinuing each agent in the combination Arm A and B must be 
recorded independently; the reason for each component of the combination may differ 
from each other.  
9.2. 
Safety Stopping Criteria 
9.2.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology (in alignment with the FDA 
premarketing clinical liver safety guidance [Food and Drug Administration, 2009]). 
Discontinuation of study treatment for abnormal liver tests is required when the 
participant satisfies any of the stopping rules as shown in Figure 8. 


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Figure 8 
Liver Stopping and Monitoring Event Algorithm 
 
Refer to Appendix 9 (Section 14.9) for required Liver Safety Actions and Follow-up Assessments. 
9.2.2. 
Study Treatment Restart or Rechallenge 
A participant who met liver chemistry stopping criteria cannot resume study intervention 
unless all of the following conditions are met: 
• 
GSK approval is granted (see Section 9.1.1), 
• 
Institutional Review Board/Independent Ethics Committee (IRB/IEC) approval 
is obtained and 
• 
Separate ICF for study intervention restart/rechallenge is signed by the 
participant and participant is informed of any associated risks 
If GSK approval to restart/rechallenge participant with study intervention is not granted, 
then participant must permanently discontinue study intervention and may continue in the 
study for protocol-specified follow up assessments. 
Refer to Study Procedural Manual for full guidance. 
9.2.3. 
QTc Interval Stopping Criteria 
If a participant that meets the corrected QT (QTc) interval duration criteria below, study 
treatment(s) will be withheld.   
• 
QTcF >530 msec 


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Based on average QTcF value of triplicate electrocardiograms (ECGs) to include manual 
over-read.  
For example, if an ECG demonstrates a prolonged QT interval, obtain 2 additional ECGs 
over a brief period (e.g., within approximately 10 min of the abnormal ECG, if possible, 
and approximately 10 min apart from each other), and then use the averaged QTc values 
of the 3 ECGs to determine whether the participants should have study treatment(s) 
withheld.  The QTc should be based on single or averaged QTc values of triplicate ECGs 
obtained over a brief (e.g., 5-10 min) recording period.   
The QT interval should be corrected for heart rate by Fridericia’s formula (QTcF).   
See the Schedule of Activities for data to be collected at the time of treatment 
discontinuation and Follow-up and for any further evaluations that need to be completed. 
9.2.4. 
Left Ventricular Ejection Fraction (LVEF) Stopping Criteria 
ECHO must be performed at Screening and then every 12 weeks (7 days), and at the 
End of Study Treatment Visit as outlined in the Schedule of Activities (Section 3). 
Participants who have an asymptomatic, absolute decrease of >10% in left ventricular 
ejection fraction (LVEF) compared with baseline and the ejection fraction is below the 
institution’s lower limit of normal (LLN) should temporarily discontinue study treatment 
and have a repeat evaluation of LVEF within 1 week.  ECHO should be repeated every 1 
to 2 weeks for 4 weeks or until LVEF recovery to above institutional LLN and within 
10% of baseline. 
• 
If the LVEF recovers (defined as LLN and an absolute decrease 10% 
compared with baseline) at any time during the next 4 weeks, after consultation 
and approval of the Medical Monitor, the participant may be restarted on study 
treatment at a reduced dose. For such participants, monitoring of LVEF will be 
performed 2 and 4 weeks after rechallenge, and every 4 weeks thereafter for 16 
weeks and then per protocol. 
• 
If repeat LVEF does not recover within 4 weeks, study treatment should be 
permanently discontinued. Ejection fraction should be monitored every 4 weeks 
for a total of 16 weeks or until resolution. 
Participants with Grade 3 or 4 (symptomatic) left ventricular systolic dysfunction must 
discontinue study treatment. Ejection fraction should be monitored every 4 weeks for a 
total of 16 weeks or until resolution. If recovery occurs (LVEF institutional LLN and 
symptom resolution) within 4 weeks, then study treatment may be restarted at a reduce 
dose in consultation with the Medical Monitor. 
ECHOs for participants who experience a >10% decrease in LVEF from baseline and 
whose cardiac ejection fraction is < institution’s LLN will be reviewed by the Sponsor. 
Instructions for submitting qualifying ECHOs are provided in the SRM. 


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9.2.5. 
Corneal Event Stopping Criteria 
Corneal events, which commonly manifests as a superficial microcystic keratopathy, has 
been observed with antibody drug conjugates, including those conjugated to MMAF.  
Further information regarding corneal event associated with belantamab mafodotin, 
including the GSK grading scale and prophylactic measures are in Appendix 8, Section 
14.8. 
All belantamab mafodotin dose modifications and stopping criteria are to be based on the 
GSK Scale provided in Appendix 8, Section 14.8. Corneal events will be graded 
according to both CTCAE criteria for eye disorders and the guidelines provided in 
Appendix 8. 
The treating physician or qualified eye care specialist (Appendix 12) must discuss the 
participants who develop a Grade 4 corneal event according to the GSK scale with the 
Medical Monitor or a GSK eye care specialist to determine whether the participant can be 
allowed to restart treatment with belantamab mafodotin or whether belantamab mafodotin 
should be permanently discontinued. If a participant is allowed to continue on study, the 
dose of belantamab mafodotin will be reduced after discussion with Medical Monitor. 
The decision will be documented in study files, together with individual assessment of 
risk-benefit. 
9.2.6. 
Infusion-Related Reaction Management and Stopping Criteria 
Premedication is not required prior to infusion unless deemed medically appropriate by 
the investigator. Premedication should be considered in any participant who experienced 
an IRR at first or any subsequent infusion with belantamab mafodotin. For infusion 
reactions of any grade/severity, immediately interrupt the belantamab mafodotin infusion 
and manage symptoms. Once reaction symptoms resolve, resume the infusion at a 
reduced rate. Premedication may be administered with subsequent infusions per 
institutional guidelines. IRRs should be managed by guidelines provided in Table 20. 
A participant that experiences a Grade 4 IRR associated with belantamab mafodotin 
should be permanently withdrawn from the study. 
9.2.7. 
Allergic and Anaphylactic Reaction Stopping Criteria 
All participants will be monitored carefully for evidence of allergic response to study 
treatments. A participant that exhibits signs or symptoms of severe hypersensitivity or 
anaphylaxis will receive appropriate medical treatment and be permanently withdrawn 
from the study. 
9.3. 
Withdrawal from the Study 
A participant may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioral, 
compliance, or administrative reasons.  


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If the participant withdraws consent for disclosure of future information, the Sponsor 
may retain and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the Investigator must document this in the site study records. 
Refer to End of Treatment & Follow-Up Assessments (Table 6) for information to be 
collected at the time of study discontinuation. 
9.4. 
Lost to Follow-Up 
A participant will be considered lost to Follow-up if they repeatedly fail to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to and/or 
should continue in the study. 
• 
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 with a primary reason of lost to Follow-up.  


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10. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the Schedule of Activities 
(Section 3). Key assessments to be performed during the study are briefly described 
below, with more detailed information provided for some specific assessments in the 
Protocol Appendices or the SRM. Protocol waivers or exemptions for study assessments 
will not be allowed.  
The investigators will maintain screening logs to record details of all participants 
screened and to confirm eligibility or record reasons for screening failure, as appropriate. 
Procedures conducted as part of the participant’s routine clinical management (e.g., blood 
count) and obtained before signing of ICF may be utilized for screening or baseline 
purposes provided the procedure met the protocol-specified criteria and was performed 
within the time frame defined in the Schedule of Activities (Table 4).   
Where applicable country and local regulations and infrastructure allow, home healthcare 
and telemedicine may be permitted (Appendix 13 Section 14.13)  
10.1. 
Assessments for Evaluation of Clinical Activity 
Clinical activity will be evaluated in all participants in the study.  Standard Response 
assessments for RRMM will be applied to clinical activity data, and will include: Overall 
Response Rate (ORR), 
 
 – as defined by 2016 IMWG 
response criteria [Kumar, 2016], and as data permits. In addition, the number (%) of 
participants achieving 
 will be assessed 
according to IMWG criteria 2011 and 2016 [Kumar, 2016], as data permits.  
Clinical activity assessments and/or diagnostic criteria will be evaluated during treatment, 
per IMWG and other current practice guidelines for the management of RRMM [Bennett, 
2016; Kumar, 2016; Moreau, 2017; National Comprehensive Cancer Network, 2016; 
Rajkumar, 2016].  These may include: 
• 
Laboratory tests (serum and urine M-protein test, immunofixation, free light chains 
[FLC])  
• 
Bone marrow (BM) aspirate/biopsy for disease assessment, 
 
 testing 
• 
Imaging for extramedullary disease and skeletal survey 
10.1.1. 
Imaging 
Imaging is only required for participants with extramedullary disease by either CT, MRI, 
or PET/CT per local guidance. The screening assessment may be performed up to 
30 days prior to C1D1. The imaging method used at baseline should be used throughout 
the study (i.e. if CT/PET scan was used as baseline, the participant should be followed by 
CT/PET scans). A selected target lesion should be measured and followed over time. 
Plasmacytoma measurements should be taken from the CT portion of the PET/CT, or 
MRI scans, or dedicated CT scans, where applicable. For participants with only skin 
CCI
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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). 
10.2. 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 6, Section 14.6. 
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study treatment or the study, 
or that caused the participant to discontinue the study treatment (see Section 9.1). 
Adverse events, including corneal events, will be graded by the investigator according to 
the NCI-CTCAE, (version 4.03). For dosing decisions, corneal events associated with 
belantamab mafodotin will also be graded according to the GSK grading scale provided 
in Appendix 8. 
10.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
All SAEs will be collected from the start of treatment until at least 70 days following 
discontinuation of study treatment regardless of initiation of a new cancer therapy or 
transfer to hospice at the time points specified in the Schedule of Activities (SoA) 
(Section 3). 
• 
However, any SAEs assessed as related to study participation (e.g., study treatment, 
protocol-mandated procedures, invasive tests, or change in existing therapy) or 
related to a GSK product will be recorded from the time a participant consents to 
participate in the study up to and including any follow-up. 
• 
All AEs will be collected from the start of treatment until at least 70 days following 
discontinuation of study treatment regardless of initiation of a new cancer therapy or 
transfer to hospice at the time points specified in the SoA. 
• 
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 h, as indicated in Appendix 6, Section 
14.6. The investigator will submit any updated SAE data to the Sponsor within 24 h 
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 
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• 
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 6, Section 14.6.  
• 
For participants in the PACT phase of the study, GSK will continue to collect safety 
information including SAEs, AEs leading to treatment discontinuation, overdose and 
pregnancy cases and pre-specified ocular data via paper forms, emails (preferably), 
and fax which will be reported directly to GSK (see SRM for details). SAE, overdose 
and pregnancy and cases will go to the Global Safety database (ARGUS). 
• 
SAEs, overdose and pregnancy cases will be reported during the PACT treatment 
period and for up to 70 days after last dose. Additionally, any SAE that are ongoing 
at the time of the final data cut-off must be followed up to resolution unless the event 
is considered by the investigator unlikely to resolve, or the patient is lost to follow-
up.   
• 
Pre-specified ocular data will continue to be collected for participants receiving 
belantamab mafodotin after the start of PACT as follows: Participants without 
significant ocular examinations findings, symptoms or vision changes when entering 
the PACT phase will be required to have an ocular assessment at least every 3 
months until the end of treatment. Participants who at the time of entering PACT 
have ocular symptoms or vision changes, or develop these during PACT treatment, 
the ocular assessment will occur every cycle until resolution (KVA Grade 1 or 
baseline). After the end of PACT treatment, participants with treatment-related 
ocular examination findings, ocular symptoms, or vision changes will be followed at 
least every 3 months for up to 12 months from the end of treatment or until 
resolution (to KVA Grade 1 or baseline), whichever comes first. For participants 
without ocular examination findings, ocular symptoms, or vision changes at the end 
of PACT treatment, no further ocular exams are required. In addition, participants 
who stopped belantamab mafodotin prior to PACT but have ongoing ocular events at 
the time of final study data-cut-off/start of PACT, will be followed at least every 3 
months for up to 12 months from the end of treatment or until resolution (KVA 
Grade 1 or baseline), whichever comes first. GSK retains the right to request 
additional information for any patient with ongoing AE(s)/SAE(s) at the end of the 
study, if judged necessary.  
10.2.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence.  
10.2.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, and non-serious AEs of special 
interest, will be followed until the event is resolved, stabilized, otherwise explained, or 
the participant is lost to Follow-up (as defined in Section 9.4). Further information on 
follow-up procedures is given in Appendix 6, Section 14.6. 


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10.2.4. 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the Sponsor of an SAE is essential so that 
legal obligations and ethical responsibilities towards the safety of participants and 
the safety of a study 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 an 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. 
10.2.5. 
Cardiovascular and Death Events 
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
For any cardiovascular events detailed in Appendix 5, Section 14.5 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 medical 
dictionary for regulatory activities (MedDRA) terms. The CV information must be 
recorded in the specific cardiovascular section of the eCRF within 1 week of receipt of a 
CV Event data query prompting its completion. 
10.2.6. 
Adverse Events of Special Interest 
Adverse events of special interest (AESI) for belantamab mafodotin are corneal events, 
thrombocytopenia and infusion related reactions.  Severity of all AESI will be graded 
using National Cancer Institute-Common Toxicity Criteria for Adverse Events (CTCAE, 
v4.03; Appendix 8). Severity of corneal events will also be graded using the GSK scale 
for corneal events provided in Table 33. Guidelines for dose modifications and 
interruptions for management of common toxicities associated with the study treatment(s) 
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10.2.7. 
Pregnancy 
Do not collect pregnancy information for female participants known to be pregnant 
during the screening phase or before exposure to study. 
The need for a screening pregnancy test depends on whether a female participant is of 
childbearing potential or non-childbearing potential. 
If a female participant is of childbearing potential, she must have a serum β-human 
chorionic gonadotropin (β –HCG) pregnancy test performed within 24 h prior to the first 
dose of study treatment. Participants with positive pregnancy test result must be excluded 
from the study. Participants with negative pregnancy test result must agree to use an 
effective contraception method as described below during the study until 4 months 
following the last dose of study treatment. 
• 
Details of all pregnancies in female participants will be collected after the start of 
study treatment and  
• 
Arm A: for 4 months following last dose of belantamab mafodotin or 4 weeks 
after the last dose of lenalidomide, whichever is longer (by telephone for 
WOCBP only) 
• 
Arm B: for 4 months following last dose of belantamab mafodotin or 7 months 
following last dose of bortezomib whichever is longer (by telephone for 
WOCBP only) 
• 
Details of all pregnancies for female partners of male participants will be collected 
after the start of study treatment and 6 months following the last dose of belantamab 
mafodotin (by telephone for WOCBP partners only) 
• 
If a pregnancy is reported, the investigator must inform GSK within 24 h of learning 
of the pregnancy and must follow the procedures outlined in Appendix 7, as well as 
those outlined in REVLIMID (lenalidomide) Patient Exposure Registry (Refer to 
SRM). 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
10.2.8. 
Medical Device Incidents (including malfunctions) 
Not applicable for this study 
10.3. 
Treatment of Overdose 
10.3.1. 
Belantamab Mafodotin Overdose 
There is no specific information on overdose of belantamab mafodotin. GSK does not 
recommend specific treatment for an overdose of belantamab mafodotin. 
In the event of an overdose (defined as administration of more than the protocol-specified 
dose) of belantamab mafodotin, the investigator should: 
• 
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• 
closely monitor the participant for AEs, SAEs, and laboratory abnormalities 
until they are resolved and belantamab mafodotin concentrations are predicted to 
be within the anticipated range in absence of the overdose  
• 
obtain an additional PK and serum 
 sample as soon as the overdose 
situation is recognized and contact the GSK Medical Monitor for further 
guidance with regards to additional sample collection (determined on a case-by-
case basis) 
• 
document the quantity of the excess dose as well as the duration of the 
overdosing in the eCRF 
Decisions regarding belantamab mafodotin or administration of SoC agents following an 
overdose will be made by the investigator in consultation with the GSK Medical Monitor 
based on the clinical evaluation of the participant. 
10.3.2. 
Lenalidomide Overdose 
There is no specific experience in the management of lenalidomide overdose in 
participants with MM. In dose-ranging studies in healthy participants, some were 
exposed to up to 200 mg (administered 100 mg BID) and in single-dose studies, some 
participants were exposed to up to 400 mg. Pruritis, urticaria, rash, and elevated liver 
transaminases were the primary reported AEs.  In clinical trials, the dose-limiting toxicity 
was neutropenia and thrombocytopenia. 
10.3.3. 
Bortezomib Overdose 
There is no known specific antidote for bortezomib over-dosage. In humans, overdose of 
more than twice the recommended dose has been associated with the acute onset of 
symptomatic hypotension and thrombocytopenia with fatal outcomes. In the event of an 
overdose, the participant’s vital signs should be monitored, and appropriate supportive 
care given to maintain blood pressure (such as fluids, pressors, and/or inotrophic agents) 
and body temperature. 
10.3.4. 
Dexamethasone Overdose 
Overdosage or prolonged use may exaggerate glucocorticoid adverse effects. Treatment 
should be symptomatic and supportive with the dosage of dexamethasone being reduced 
or slowly withdrawn where possible. 
10.4. 
Demographics and Medical History 
Demographic and medical history data will be collected at Screening and verified pre-
dose on Day 1 Cycle 1 in both Part 1 and Part 2. 
Demographic data we can collect may differ in different regions but should include: year 
of birth, sex, and race/ethnicity (if permitted). The medical history data that may be 
collected can be divided into two sections: 
• 
Standard Medical History of Prior Conditions: may include the condition/diagnosis, 
body system (if appropriate), date of diagnosis, intensity (if appropriate), date of 
resolution, and any interventions or treatments (with dates). 
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• 
History of RRMM and Current Comorbid Conditions may include: the 
condition/diagnosis (for non-RRMM), body system (if appropriate, for non-RRMM), 
date of diagnosis, intensity or Grade (as appropriate), prior treatment regimens with 
start and stop dates, and any interventions or treatments. 
10.5. 
Daily Study Diary 
Depending on assigned treatment, participant will be issued Daily Study Diary that will 
be reviewed at each clinic visit. Participant Diary will be used to record drug 
accountability information: doses of lenalidomide or dexamethasone taken at home 
during a treatment cycle; drug name, dose (or number of tablets or capsules), the date the 
dose was taken, and the time the dose was taken will all be recorded in the Diary. 
10.6. 
Safety Assessments 
10.6.1. 
Physical Examinations 
Physical examinations will be performed during Screening, pre-dose on Day 1 (and on 
Day 8 for SPLIT dosing) of each Cycle, and upon discontinuation form Study Treatment 
(End of Treatment Visit and 
 FU Visit). A physical examination 
will include, at a minimum, assessments of the head, eyes, ears, nose, throat, skin, 
thyroid, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes and extremities. 
Height and weight will also be measured at Screening and recorded, with weight repeated 
at the start of each cycle (Schedule of Activities, Section 3). Body weight at C1D1 (prior 
to dosing) will be used for dose calculation of belantamab mafodotin. Body weight will 
also be measured prior to each dose. If the change of body weight is greater than 10%, 
the dose should be re-calculated based on the actual body weight at the time of dosing. 
During the physical examinations, investigators should pay special attention to clinical 
signs related to previous serious illnesses and record any changes noted during study 
treatment, if any. 
10.6.2. 
ECOG Performance Status 
The participant’s performance status will be assessed using the ECOG scale (Appendix 3, 
Section 14.3) as specified in the Schedule of Activities (Section 3). 
10.6.3. 
Vital Signs 
Vital sign measurements will include systolic and diastolic blood pressure, temperature, 
and heart rate. Vital signs should be measured after resting for at least 5 min. Vital signs 
will 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. 
On each dosing day, vital signs must be assessed prior to each infusion of belantamab 
mafodotin at pre-dose, defined as within 30 min prior to start of infusion (SOI), within 15 
min after End of Infusion (EOI), and at 1 h (±5 min) after EOI. On days where 
bortezomib is administered, vital signs must be assessed within 30 mins prior and within 
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15 min after each dose of bortezomib. On days where vital sign time points align with PK 
sampling time points, vital signs should be assessed prior to PK samples being drawn. 
In general, participants must also be monitored for at least 1 h after the completion of the 
infusion of belantamab mafodotin and may be discharged if considered clinically stable 
and all other study procedures have been completed. 
In case of IRRs monitoring will be performed with higher frequency (as clinically 
indicated). 
10.6.4. 
New York Heart Association Functional Scale 
Criteria for rating participants for heart failure status according to the New York Heart 
Association (NYHA) criteria are provided in Appendix 5, Section 14.5. 
10.6.5. 
Electrocardiograms 
Triple 12-lead electrocardiogram (ECGs) will be obtained at designated time points 
specified in the Schedule of Activities (Section 3) during the study using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and 
corrected QT (QTc) intervals.   
At each assessment, a 12-lead ECG will be performed by qualified personnel at the site 
after the participant has at least a 5-min rest.   
The QT interval should be corrected for heart rate by Fridericia’s formula (QTcF). Refer 
to Section 9.2.3 for QTc withdrawal criteria. Refer to the Study Procedures Manual for 
details regarding ECG procedures. 
Instructions for submission of ECGs are provided in the SRM. 
10.6.6. 
Echocardiogram 
ECHOs must be performed at baseline and then every 12 weeks ( 7 days) to assess 
cardiac ejection fraction for the purpose of study eligibility, as specified in the SoA. A 
final ECHO will also be performed at the End of Treatment Visit. 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.  
10.6.7. 
Ophthalmic Examinations 
Study sites are required to establish a close collaboration with a qualified eye care 
specialist who will be responsible for assessing participants while they are on-study and 
managing participants who develop a corneal event in close communication with the 
GSK Medical Monitor. Participants will be assessed by a qualified eye care specialist at 
screening/baseline and then on Day 1 of every cycle prior to belantamab mafodotin 
dosing up to Dose 6 of belantamab mafodotin (assessment window of up to 5 days prior 
to dosing, but all effort should be made to schedule as close to belantamab mafodotin 
dosing as possible). For STRETCH schedule, belantamab mafodotin dosing is scheduled 


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on Day 1 of every alternate 21-day cycle, but participants will be assessed by a qualified 
eye care specialist on Day 1 of every 21-day cycle up to the Dose 6 of belantamab 
mafodotin  regardless of dosing (assessment window of up to 5 days before Day 1 of 
every 21-day cycle prior to dosing, but all effort should be made to schedule as close to 
belantamab mafodotin dosing as possible). See Appendix 12 for qualifications and 
requirements of the eye care specialist. 
• 
If there are no significant ocular examinations findings, patient’s symptoms or 
vision changes at the time of the Dose 6 exam, participants may have their 
ophthalmologic exams decreased to once every 3 months.  
• 
If a participant subsequently develops vision changes or other ocular symptoms, 
the participant should be promptly evaluated by a qualified eye care specialist. 
• 
In case of persistent ophthalmic exam findings, newly developed ocular 
symptoms or vision changes at the Dose 6 exam, the participants will have 
further ophthalmologic exams, at least every cycle until resolution (to Grade 1 
or baseline) or more frequently as clinically indicated by the qualified eye care 
specialist. 
Participants who have corneal signs per the GSK scale for Corneal Events at the End of 
Treatment Visit will be followed once every 3 months (7 days) until full resolution of 
ophthalmic changes (Grade 1 or baseline) by a qualified eye care specialist or start a new 
anti-cancer therapy, or up to 1 year (whichever comes first). 


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10.6.7.1. 
Ocular Examinations and Procedures 
A full screening/ baseline ophthalmic examination for all participants must include for 
both eyes (OU): 
1. Best corrected visual acuity  
2. Documentation of manifest refraction and the method used to obtain best corrected 
visual acuity 
3. Current glasses prescription (if applicable) 
4. Anterior segment (slit lamp) examination with focus on the cornea and lens, including 
fluorescein staining of the cornea  
5. Intraocular pressure measurement 
6. Dilated funduscopic exam 
The on treatment and follow-up ophthalmic exam should be performed for both eyes 
(OU), as described below (and in the SoA) and must include:  
1. Best corrected visual acuity 
2. Documentation of manifest refraction and the method used to obtain best corrected 
visual acuity 
3. Anterior segment (slit lamp) examination with focus on the cornea and lens, 
including fluorescein staining of the cornea 
4. Intraocular pressure measurement (if clinically indicated) 
5. Dilated funduscopic exam (if clinically indicated) 
The end of treatment and last follow-up ophthalmic exam should match the screening/ 
baseline exam. 
Additional examinations should be performed at the discretion of the treating eye 
specialist.  
10.6.8. 
Patient-Reported Outcome Version of the Common Term Criteria 
for Adverse Events (PRO-CTCAE) 
The Patient-Reported Outcomes Version of the Common Terminology Criteria for 
Adverse Events is a patient-reported outcome measure developed to evaluate 
symptomatic toxicity in patients on cancer clinical trials [Basch, 2014]. The PRO-
CTCAE was designed to be used as a companion to the Common Terminology Criteria 
for Adverse Events (CTCAE), the standard lexicon for adverse event reporting in cancer 
trials. The PRO-CTCAE includes an item library of 124 items representing 80 
symptomatic toxicities drawn from the CTCAE.  PRO-CTCAE provides a systematic yet 
flexible tool for descriptive reporting of symptomatic treatment side effects in cancer 
clinical trials. In the present study, a subset of items selected from the PRO-CTCAE 
Version 1.0 item library will be administered, as shown in the Schedule of Activities 
(Section 3). The PRO-CTCAE will be administered to participants in different regions 
based on the availability of translated versions. All participants will complete the self-


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administered version of this assessment unless they are unable to do so due to site 
restrictions or the PI or site feels it is in the best interest of the participant not to come to 
the site. Participants who cannot complete the self-administered version should use an 
Interviewer-Administered format. The interview may be administered over the telephone. 
If the Interviewer-Administered format is used, it should be read to the participants 
verbatim, and participant responses should be recorded directly without any 
interpretation. 
10.6.9. 
Visual Function Safety Assessment 
The impact of potential ocular toxicity on function and health-related quality of life will 
be assessed with the use of 2 visual function questionnaires: the National Eye Institute 
Visual Function Questionnaire-25 (NEI-VFQ-25), and the Ocular Surface Disease Index 
(OSDI). All participants will complete the self-administered version of these two 
assessments, unless their vision prevents them from being able to complete the 
questionnaire on their own, they are unable to complete the self-administered version due 
to site restrictions, or the PI or site feels it is in the best interest of the participant not to 
come to the site. Participants who are not able to complete the self-administered version 
should use an Interviewer-Administered format. If the Interviewer-Administered format 
is used, it should be read to the participants verbatim, and participant responses should be 
recorded directly without any interpretation. For any additional assessments conducted 
via telephone (either during participation in the treatment period or during Follow-up), 
the Interviewer-Administered format should be used. 
10.6.9.1. 
National Eye Institute Visual Function Questionnaire-25 
The NEI-VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 
vision-related constructs, plus an additional single-item general health rating question. 
These include a global vision rating (1 item); difficulty with near vision activities (3 
items); difficulty with distance vision activities (3 items); limitations in social functioning 
due to vision (2 items); role limitations due to vision (2 items); dependency on others due 
to vision (3 items); mental health symptoms due to vision (4 items); driving difficulties (3 
items); limitations with peripheral vision (1 item), limitations with color vision (1 item); 
and Ocular pain (2 items). The NEI-VFQ-25 will be completed by the participants at the 
times shown in the Schedule of Activities (Section 3). 
10.6.9.2. 
The Ocular Surface Disease Index 
The Ocular Surface Disease Index (OSDI) is a 12-item questionnaire designed to assess 
both the frequency of dry eye symptoms and their impact on vision-related functioning 
[Dougherty, 2011, Schiffman, 2000]. The OSDI has demonstrated good reliability, 
validity, sensitivity, and specificity, and can be used as a complement to other clinical 
and participative measures of dry eye disease by providing a quantifiable assessment of 
dry eye symptom frequency and the impact of these symptoms on vision-related 
functioning. The OSDI will be completed by the participants at the times shown in the 
Schedule of Activities (Section 3). 
 


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10.6.10. 
Laboratory Assessments 
All protocol-required laboratory assessments should be performed according to the 
Schedule of Activities (Section 3). 
Details for the preparation and shipment of samples are provided in the SRM. 
Local laboratory results will be used to make decisions regarding treatment or 
management of AEs.  
Prior to administration of the first dose of study treatment, results of laboratory 
assessments should be reviewed.  Any laboratory test with a value outside the normal 
range may be repeated (prior to the first dose) at the discretion of the Investigator. 
If additional non-protocol-specified laboratory assessments are performed at the 
institution’s local laboratory and result in a change in participant management or are 
considered clinical significant by the investigator (for example SAE or AE or dose 
modification) the results must be recorded in the participant’s CRF. Clinically significant 
abnormal laboratory findings are those which are not associated with the underlying 
disease, unless judged by the investigator to be more severe than expected for the 
participant’s condition.  
All laboratory tests with values that are significantly abnormal during participation in the 
study or within 70 days after the last dose of study treatment should be repeated until the 
values return to normal or baseline. If such values do not return to normal within a period 
judged reasonable by the Investigator, the etiology should be identified and the Sponsor 
notified. 
Hematology, clinical chemistry, urinalysis and additional parameters to be tested are 
listed in Table 27 with detailed instructions and timing in the SRM. 
Refer to the SRM for appropriate processing and handling of samples to avoid duplicate 
and/or additional blood draws. 
Table 27 
List of Clinical Laboratory Tests 
Hematology1 
Platelet Count  
Red Blood Cell 
(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 


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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 
Urinalysis1 
Specific gravity; pH, glucose, protein, blood and ketones by dipstick 
Microscopic examination (if blood or protein is detected by dipstick) 
Other Laboratory Tests 
Spot urine (albumin/creatinine ratios) 1, 3; HbA1c1; C-reactive protein (CRP)1; Pregnancy Test (urine or 
blood)1; Follicle-stimulating hormone (FSH)1 and estradiol1 (as needed in women of non-child-bearing 
potential only); Hepatitis B (HbsAg)1; HbcAb, Hepatitis C antibody1, Hepatitis C RNA test1 (optional) 
Note: Hep C RNA testing is optional but may be done to determine participant eligibility if Hep C antibody 
positive. 
eGFR
1 
PK and ADA
2 
Pharmacokinetics (PK) 
Anti-Drug Antibodies (ADA) 
Disease Evaluation Laboratory Tests1, 3 
Beta2 microglobulin; SPEP (Serum Protein Electrophoresis); Serum M-protein calculation; Serum Kappa, 
lambda free LC, FLC ratio; Serum Immunofixation; UPEP (Urine Protein Electrophoresis); 24-h urine 
collection for M-protein; Urine Immunofixation; Ca corrected for Albumin (Serum); IgG, IgM, IgA, IgD/IgE
4  
Bone Marrow Aspiration/Biopsy 
BM for FISH analysis
1, 3, 5; BM aspirate for BCMA expression and biomarker research
2; BM biopsy to 
confirm sCR (by IHC)
 2; BM aspirate for 
 testing
2 
Biomarker Measurements2   
 Genetic Sample6 
1. 
To be performed at local laboratory 
2. 
To be performed at central laboratory 
3. 
If not available locally it can be performed centrally 
4. 
Only for participants with IgD/E myeloma 
5. 
FISH testing at least for: t(4;14), t(14;16), amp(1q), del(1p) and del(17p13).  If participant is known to have 
tested positive for t(4;14) or  t(14/16) on previous tests regardless of timeframe, FISH for these 
translocations does not need to be repeated. FISH results for amp(1q), del(1p) and del(17p13) from 
samples taken within 60 days prior to first dose are acceptable. 
6. 
Informed consent for optional sub-studies (e.g. genetic research) must be obtained before collecting a 
sample. 
 
10.6.11. 
DNA Sampling for Genetic Testing 
Genetic variation may impact a participant’s response to therapy, susceptibility, severity 
and progression of disease. Variable response to therapy may be due to genetic 
determinants that impact drug absorption, distribution, metabolism, and excretion; 
mechanism of action of the drug; disease etiology; and/or molecular subtype of the 
disease being treated. Therefore, where local regulations and IRB/IEC allow, and pending 
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the consent of the participant, a 6 mL of blood sample will be collected for DNA 
analysis. If insufficient DNA is extracted from the original sample, or if the sample was 
damaged or otherwise could not be processed, the site may be requested to recollect the 
genetic sample where applicable and if the participant consents.   
DNA samples will be used for research related to belantamab mafodotin or RRMM and 
related diseases. They may also be used to develop tests/assays including diagnostic tests) 
related to belantamab mafodotin and RRMM. Detailed Guidance relating to sampling, 
analysis of genetic material in this study is provided in Appendix 10 – Genetics. 
Genetic research may consist of the analysis of one or more candidate genes or the 
analysis of genetic markers throughout the genome (or analysis of the entire genome as 
appropriate).  DNA samples will be analyzed by using appropriate descriptive and/or 
statistical analysis methods. A detailed description of any planned analyses will be 
documented in a RAP prior to initiation of the analysis.  Additional analyses may be 
conducted if it is hypothesized that this may help further understand the clinical data.  
The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to belantamab mafodotin or study treatments of this class. The 
results of genetic analyses may be reported in the clinical study report or in a separate 
study summary. 
The Sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality.  
The samples will be retained while research on belantamab mafodotin (or study 
treatments of this class) or RRMM continues but no longer than 15 years after the last 
participant last visit or other period as per local requirements. 
10.6.12. 
Suicidal Risk Monitoring 
Not applicable. 
10.7. 
Pharmacokinetics 
10.7.1. 
Blood Sample Collection for Pharmacokinetics 
Blood samples for pharmacokinetic (PK) analysis of belantamab mafodotin (ADC and 
total antibody) and cys-mcMMAF will be collected for all participants at the time points 
indicated in the Schedule of Activities tables (Section 3). 
For participants assigned to Arm A and receiving belantamab mafodotin Q4W, additional 
blood samples for lenalidomide pharmacokinetics will also be collected at Cycle 1 at the 
time points indicated in SoA (Table 5).  
For participants assigned to Arm B and receiving belantamab mafodotin Q3W, additional 
blood samples for bortezomib pharmacokinetics will be also collected at Cycle 1 at the 
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Each PK sample should be collected as close as possible to the planned time relative to 
the administration of the drug being measured on PK days (i.e., belantamab mafodotin 
samples collected relative to belantamab mafodotin dosing, lenalidomide samples 
collected relative to lenalidomide dosing, and bortezomib samples collected relative to 
bortezomib dosing). The actual date and time of each blood sample collection will be 
recorded. Details on PK blood sample collection including blood volumes, processing, 
storage, and shipping procedures are provided in the SRM. 
 samples should be collected at all PK time points as close as 
possible to the belantamab mafodotin PK sample. 
All PK, 
 and ADA samples once collected (regardless of dosing) will be 
analyzed if the sample date and time have been recorded. 
10.7.2. 
Pharmacokinetic Sample Analysis 
Plasma analysis will be performed under the control of GSK, the details of which will be 
included in the SRM. Concentrations of belantamab mafodotin (ADC and total antibody) 
and cys-mcMMAF will be determined in plasma samples using the currently approved 
bioanalytical methodology. Concentrations of lenalidomide and bortezomib will be 
determined in plasma samples using validated bioanalytical methods. Raw data will be 
archived at the bioanalytical site (as described in the SRM). 
Once the plasma has been analyzed for belantamab mafodotin (ADC and total antibody) 
and cys-mcMMAF, any remaining plasma may be analyzed for other compound-related 
metabolites and the results reported separately. 
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10.9. 
Immunogenicity Assessments 
Serum samples for determination of anti- belantamab mafodotin antibodies will be taken 
from all participants at the time points specified in the Schedule of Activities (Section 3). 
These samples will be tested by the sponsor or sponsor’s designee.  
Anti-belantamab mafodotin antibody samples will be tested for anti-belantamab 
mafodotin antibodies using a tiered-testing scheme consisting of validated screening, 
confirmation, and titration assays.  Briefly, all samples will be tested in the screening 
assay.  Samples that screen positive are considered potentially positive and will be tested 
for specificity in a confirmation assay.  Finally, titer values will be obtained for 
confirmed positive samples using a titration assay.  The sample results (e.g., positive or 
negative) and titer values (positive samples only) will be reported.  Samples that test 
positive for anti-belantamab mafodotin antibodies may be further characterized in a 
validated neutralizing antibody assay to determine the neutralizing activity of the 
antibodies.   
The detection and characterization of antibodies to belantamab mafodotin will be 
performed using validated assays. The anti-belantamab mafodotin antibody assay was 
designed to detect antibodies to belantamab mafodotin, the unconjugated monoclonal 
antibody and the linker-payload portion of the belantamab mafodotin.  Additionally, 
plasma samples will be collected at the same time points (see SoA) as the 
immunogenicity samples and analyzed to determine the belantamab mafodotin plasma 
concentration.  The belantamab mafodotin plasma concentration results will enable 
interpretation of the anti-belantamab mafodotin antibody data.  Anti-belantamab 
mafodotin antibody samples will be disposed three months after final approved results are 
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provided to the Clinical Study Team or its designee or upon documented study 
termination. 
10.11. 
Health-Related Quality of Life 
Two validated health-related quality of life (QoL) instruments will be employed in this 
study, to assess disease severity, disease symptoms, adverse events associated with the 
study treatment, and general quality of life in study participants with RRMM assigned to 
either Arm A or Arm B. All participants will complete the self-administered version of 
these assessments unless they are unable to do so due to site restrictions or the PI or site 
feels it is in the best interest of the participant not to come to the site. Participants who 
cannot complete the self-administered version should use an Interviewer-Administered 
format. The interview may be administered over the telephone. If the Interviewer-
Administered format is used, it should be read to the participants verbatim, and 
participant responses should be recorded directly without any interpretation. 
10.11.1. 
European Organisation for Research and Treatment of Cancer 
Quality of Life Questionnaires  
The symptoms related to multiple myeloma and its treatment, and the impact of these 
symptoms on daily functioning will be assessed using the European Organisation for 
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Research and Treatment of Cancer Quality of Life Questionnaires; EORTC QLQ-C30 
and QLQ-MY20. The EORTC QLQ-C30 AND QLQ-MY20 will be completed at the 
times shown in the Schedule of Activities (Section 3). 
10.11.1.1. European Organisation for Research and Treatment of Cancer Quality 
of Life Questionnaire 30-item Core Module (EORTC QLQ-C30) 
The EORTC QLQ-C30 is a 30-item questionnaire containing both single- and multi-item 
measures [Aaronson, 1993]. These include five functional scales (Physical, Role, 
Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and 
Nausea/Vomiting), a Global Health Status/QoL scale, and six single items (Constipation, 
Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). Scores for each 
scale and single-item measure are averaged and transformed linearly to a score ranging 
from 0–100. A high score for functional scales and for Global Health Status/QoL 
represent better functioning ability or HRQoL, whereas a high score for symptom scales 
and single items represents significant symptomatology [Proskorovsky, 2014]. 
10.11.1.2. European Organisation for Research and Treatment of Cancer Quality 
of Life Questionnaire 20-item Multiple Myeloma Module (EORTC QLQ-
MY20) 
The EORTC QLQ-MY20 is a supplement to the QLQ-C30 instrument used in 
participants with multiple myeloma [Aaronson, 1993; Cocks, 2007]. The module 
comprises 20 questions that address four myeloma-specific HRQoL domains: Disease 
Symptoms, Side Effects of Treatment, Future Perspective, and Body Image. Three of the 
four QLQ-MY20 domains are multi-item scales: Disease Symptoms (includes bone aches 
or pain, back pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with 
activity); Side Effects of Treatment (includes drowsiness, thirst, feeling ill, dry mouth, 
hair loss, upset by hair loss, tingling hands or feet, restlessness/agitation, acid 
indigestion/heartburn, and burning or sore eyes); and Future Perspective (includes worry 
about death and health in the future, and thinking about illness). The Body Image scale is 
a single-item scale that addresses physical attractiveness. As with the QLQ-C30, QLQ-
MY20 domain scores are averaged and transformed linearly to a score ranging from 0–
100. A high score for Disease Symptoms and Side Effects of Treatment represents a high 
level of symptomatology or problems, whereas a high score for Future Perspective and 
Body Image represents better outcomes [Proskorovsky, 2014]. 
11. 
DATA MANAGEMENT 
For this study participant data will be entered into GSK-defined CRFs, transmitted 
electronically to GSK or designee and combined with data provided from other sources in 
a validated data system.   
Management of clinical data will be performed in accordance with applicable GSK 
standards and data cleaning procedures to ensure the integrity of the data, e.g., removing 
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Adverse events and concomitant medications terms will be coded using MedDRA 
(Medical Dictionary for Regulatory Activities) and an internal validated medication 
dictionary, GSKDrug.   
CRFs (including queries and audit trails) will be retained by GSK or designee and copies 
will be sent to the Investigator to maintain as the Investigator copy.  Participant initials 
will not be collected or transmitted to GSK according to GSK policy. 
12. 
STATISTICAL CONSIDERATIONS 
This section briefly describes the planned analyses to be performed for Study 207497.  
Statistical analyses will either be performed separately or by combining data from Part 1 
(Dose Escalation) and Part 2 (Dose Expansion) as well as being performed independently 
for Arm A and Arm B. 
Actual analyses to be performed for each Treatment may be dependent on the outcomes 
of Part 1 and Part 2 for both Arm A and Arm B.  Ultimately those analyses will be 
described fully in the Reporting and Analysis Plan (RAP) that will be finalized prior to 
the final database release or interim database release. 
12.1. 
Hypothesis(es) 
12.1.1. 
Arm A – Belantamab Mafodotin with Len/Dex 
12.1.1.1. 
Part 1 
No formal statistical hypotheses are being tested in Part 1. Analysis of the data obtained 
from Part 1 will only utilize descriptive methods.   
12.1.1.2. 
Part 2  
No formal statistical hypotheses are being tested in Part 2. Analysis of the data obtained 
from Part 1 will only utilize descriptive methods.   
For Part 2, the number of participants who permanently discontinue study treatment due 
to AEs related to belantamab mafodotin within the first two cycles will be continuously 
monitored. For STRETCH dosing schedule, a cycle is a SoC cycle of 28 days. If the 
observed number of participants permanently discontinuing belantamab mafodotin is 
significantly higher than 12% (at 1-sided alpha of 0.01), then the combination treatment 
at that dose level or higher dose level will be considered to have unacceptable toxicity 
and the dose level as well as higher dosed levels will be closed. 
12.1.2. 
Arm B – Belantamab Mafodotin with Bor/Dex 
12.1.2.1. 
Part 1 
No formal statistical hypotheses are being tested in Part 1.  Analysis of the data obtained 
from Part 1 will only utilize descriptive methods.   


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12.1.2.2. 
Part 2 
No formal statistical hypotheses are being tested in Part 2.  Analysis of the data obtained 
from Part 2 will only utilize descriptive methods.   
For Part 2, the number of participants who permanently discontinued study treatment due 
to AE related to belantamab mafodotin within the first two cycles will be continuously 
monitored starting from when 5 participants are dosed. For STRETCH dosing schedule, a 
cycle is a SoC cycle of 21 days. If the observed number of participants permanently 
discontinuing belantamab mafodotin is significantly higher than 12% (at 1-sided alpha of 
0.01), then the combination treatment at that dose level or higher dose level will be 
considered to have unacceptable toxicity and the dose level as well as higher dose levels 
will be closed. 
12.2. 
Sample Size Determination 
12.2.1. 
Arm A – Belantamab Mafodotin with Len/Dex 
12.2.1.1. 
Part 1 
The total number of participants to be enrolled into Part 1 will depend on the number of 
participants needed to characterize individual dose cohorts. The sample size is not driven 
by statistical considerations.  However, based on assumptions that 2 different dose levels 
will be evaluated, it is anticipated that approximately 14 evaluable participants will be 
enrolled in Part 1. 
12.2.1.2. 
Part 2 
The sample size is not driven by statistical considerations. Up to 2 dose levels and up to 3 
dosing schedules will be evaluated, approximately 9 participants each will be enrolled at 
the 2.5 mg/kg SINGLE and,  2.5 mg/kg SPLIT dose levels.  
• 
In addition, an alternate dosing schedule of STRETCH (Q8W) dosing may be 
explored for the 1.9 mg/kg dose level if emerging data (from either this study or 
across the program) suggests that this schedule may further optimize the tolerability 
or offers an improved benefit/risk profile. Up to 12 participants will be enrolled in 
this new cohort.  
Approximately 31 participants will be enrolled in Part 2. 
12.2.2. 
Arm B – Belantamab Mafodotin with Bor/Dex 
12.2.2.1. 
Part 1 
The total number of participants to be enrolled into Part 1 will depend on the number of 
participants needed to characterize individual dose cohorts. The sample size is not driven 
by statistical considerations.  However, based on assumptions that 2 different dose levels 
will be evaluated, an additional lower dose level may be explored using the mTPI design. 
It is anticipated that approximately 13 evaluable participants will be enrolled in Part 1. 


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12.2.2.2. 
Part 2 
The sample size is not driven by statistical considerations. Up to 3 dose levels and up to 4 
dosing schedules will be evaluated and up to 12 participants will be enrolled at each 
dosing schedule (up to 9 participants in the 3.4 mg/kg SINGLE), it is anticipated that 
approximately 94 participants will be enrolled in Part 2. 
12.2.3. 
Sample Size Sensitivity 
There is no need to perform sample size sensitivity analysis. 
12.2.4. 
Sample Size Re-estimation or Adjustment 
Sample size re-estimation is not planned for this study. 
12.3. 
Populations for Analyses 
For purposes of analysis, the following populations are defined in Table 28.  Each of the 
following population will be created separately for Arm A and Arm B and by each part as 
appropriate.  Additional analysis populations may be defined in the RAP. 
Table 28 
Definitions of Study Analysis Populations 
Population 
Description 
All Screened  
All participants who sign the ICF to participate in the clinical trial. 
Participants in this population will be used for screen failure summary. 
All Treated 
All participants who take at least 1 dose of any study treatment. 
Analyses of demographic, baseline characteristics, safety and all 
efficacy endpoints will be based on this population. 
Pharmacokinetic 
Participants in the All Treated Population from whom at least one PK 
sample was obtained, analyzed, and was measurable. Separate PK 
populations will be defined for each drug (belantamab mafodotin, 
lenalidomide, and bortezomib). This population will be the primary 
population for PK analyses. 
 
12.4. 
Statistical Analyses 
All statistical analyses will be performed by GSK (sponsor) or under the authority of the 
Sponsor.  A general description of the statistical methods to be used to analyze the 
clinical activity and safety data is outlined below. Statistical analyses will be performed 
for each treatment group separately. There will be no comparison between treatment 
groups or parts.  
Data will be listed and summarized mostly by doses. In general, separate analyses will be 
provided for Part 1 and Part 2 where applicable.  Data from Part 1 and Part 2 may be 


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combined at interim, and final analyses. Final analysis will be performed following 12 
months post LSFD. 
Specific details will be provided in the Reporting and Analysis Plan (RAP). 
12.4.1. 
Analyses of Clinical Activity 
The primary endpoint for Part 2 will be based on the responses assessed by the 
investigator.  
The primary efficacy endpoint will be analyzed based on the All Treated Population 
unless otherwise specified. 
The analytical methods planned for the primary efficacy endpoint are described in Table 
29. 
Table 29 
Statistical Analysis Methods for Clinical Activity Endpoints (Part 2) 
Endpoint 
Statistical Analysis Methods 
Primary 
Overall Response Rate (ORR) defined as percentage (%) of participants with a 
confirmed PR or better (i.e., PR, VGPR, CR and sCR), according to the International 
Myeloma Working Group (IMWG) Response Criteria). 
The number and percentage of participants in the following response categories will be 
presented: sCR, CR, VGPR, PR, overall response (sCR+CR+VGPR+PR), minimal 
response (MR), stable disease (SD), progressive disease (PD), and not evaluable 
(NE). The corresponding 95% CI for ORR will also be provided. Participants with 
unknown or missing responses will be treated as non-responders, i.e., these 
participants will be included in the denominator when calculating percentages of 
response.  
 
12.4.2. 
Safety Analyses 
All safety analyses will be performed on the All Treated Population.  Complete details of 
the safety analyses will be provided in the RAP. 
12.4.2.1. 
Exposure Duration 
The number of participants administered study treatment will be summarized for Arm A 
and Arm B independently, according to the duration of therapy.   
12.4.2.2. 
Adverse Events 
All adverse events whether serious or non-serious, will be collected from the start of 
treatment until at least 70 days following discontinuation of study treatment regardless of 
initiation of a new cancer therapy or transfer to hospice at the time points specified in the 
Schedule of Activities (SoA).  AEs will be recorded using standard medical terminology 
and graded according to the NCI-CTCAE, Version 4.03. For AE reporting, the verbatim 


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term used in the CRF by investigators to identify adverse events will be coded using the 
latest version of Medical Dictionary for Regulatory Activities (MedDRA) coding 
dictionary. 
12.4.2.3. 
Clinical Laboratory Evaluations 
The evaluation of clinical laboratory tests will focus on selected laboratory analytes from 
the hematology and blood chemistry panel. 
Descriptive statistics (mean, standard deviation, median, range) will be used to 
summarize observed laboratory values and change from baseline in observed value at 
each scheduled visit or worst-case postbaseline, as appropriate. 
The worst-case toxicity grade in hematology and chemistry results during the treatment 
will be summarized according to NCI-CTCAE, Version 4.03 [National Cancer Institute, 
2010]. Shift tables from baseline to the worst toxicity grade during treatment will be 
provided for each laboratory analyte as appropriate. Laboratory test results outside the 
reference ranges that do not have associated NCI-CTCAE criteria will be summarized 
using proportions.  Further details will be provided in the RAP. 
12.4.2.4. 
Other Safety Measures 
Data for vital signs, ECGs and ECHOs will be summarized. For continuous variables, 
these summaries will include sample size, mean, median, standard deviation, minimum, 
and maximum. For categorical variables, the summaries will include frequencies and 
corresponding percentages. Further details will be provided in the Reporting and Analysis 
Plan (RAP). 
12.4.3. 
Pharmacokinetic Analyses 
12.4.3.1. 
Belantamab mafodotin pharmacokinetic 
Belantamab mafodotin pharmacokinetic data will be reported separately for Arm A and 
Arm B as well as combined, if appropriate. 
Concentration-Time Data: Linear and semi-logarithmic individual concentration-time 
profiles and mean and median profiles (when appropriate) will be plotted for belantamab 
mafodotin (ADC and total mAb) and cys-mcMMAF). Concentrations of belantamab 
mafodotin (ADC and total mAb) and cys-mcMMAF) will be listed for each participant 
and summarized (when appropriate) by planned time point and dose level. 
Derived Pharmacokinetic Parameters:  Pharmacokinetic analyses will be the 
responsibility of Clinical Pharmacokinetics/Modelling and Simulation, GSK. Plasma 
belantamab mafodotin (ADC, total mAb) and cys-mcMMAF concentration-time data will 
be analysed using standard noncompartmental methods, data permitting.  
Pharmacokinetic parameters will be listed and summarized descriptively (mean, standard 
deviation, median, minimum, maximum, geometric mean, and the standard deviation, 
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Plasma belantamab mafodotin, total mAb, and/or cys-mcMMAF concentration-time data 
may be combined with data from other studies and analyzed using a population 
pharmacokinetic approach. The initial analysis will use the then-current population 
pharmacokinetic model to generate post hoc pharmacokinetic parameter estimates. 
Summary exposure measures (e.g., Cmax, AUC) will also be computed.  Results of this 
analysis may be provided in a separate report. 
12.4.3.2. 
Lenalidomide 
Concentration-Time Data:  Linear and semi-logarithmic individual concentration-time 
profiles and mean and median profiles (when appropriate) will be plotted for 
lenalidomide. Concentrations of lenalidomide will be listed for each participant and 
summarized (when appropriate) by planned time point. 
Derived PK Parameters:  Lenalidomide pharmacokinetics in the presence of 
belantamab mafodotin will be analyzed using standard noncompartmental methods, data 
permitting, or using a published population pharmacokinetic model [Guglieri-Lopez, 
2017]. Results of the population PK analysis, if performed, may be provided in a separate 
report. 
Pharmacokinetic parameters will be listed and summarized descriptively (mean, standard 
deviation, median, minimum, maximum, geometric mean, and the standard deviation, 
CV%, and 95% CI of log-transformed parameters) by dose level, if appropriate. 
12.4.3.3. 
Bortezomib 
Concentration-Time Data:  Linear and semi-logarithmic individual concentration-time 
profiles and mean and median profiles (when appropriate) will be plotted for bortezomib. 
Concentrations of bortezomib will be listed for each participant and summarized (when 
appropriate) by planned time point. 
Derived PK Parameters: Bortezomib pharmacokinetics in the presence of belantamab 
mafodotin will be analyzed using standard noncompartmental methods, data permitting.   
Pharmacokinetic parameters will be listed and summarized descriptively (mean, standard 
deviation, median, minimum, maximum, geometric mean, and the standard deviation, 
CV%, and 95% CI of log-transformed parameters) by dose level, if appropriate. 
12.4.4. 
Pharmacokinetic/PD Analyses 
If deemed appropriate and if data permit, exposure-response relationships between 
belantamab mafodotin exposure (e.g., dose, dose intensity, concentration, Cmax, or 
AUC) and clinical activity and/or toxicity (e.g., response, corneal event) may be explored 
using population methods; data from this study may be combined with data from other 


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studies for these analyses. If data permit, the effects of covariates may be explored. 
Results may be reported separately. 
12.4.5. 
Translational Research Analyses 
The results of translational research investigations will be reported either within or 
separately from the main clinical study report (CSR). All endpoints of interest from all 
comparisons will be descriptively and/or graphically summarized as appropriate to the 
data. Further details on the translational research analyses will be addressed in the RAP. 
12.4.5.1. 
Novel Biomarker(s) Analyses 
The results of these biomarker investigations may be reported separately from the main 
CSR. All endpoints of interest from all comparisons will be descriptively and/or 
graphically summarized as appropriate to the data. Additional exploratory analyses may 
be performed to further characterize novel biomarkers. 
12.4.5.2. 
Genetic Analyses 
Further details on genetic analyses can be found in Section 10.10 
12.4.6. 
Immunogenicity Assessment 
For each participant, the results and titers of anti- belantamab mafodotin binding 
antibodies will be listed for each assessment time point, along with plasma belantamab 
mafodotin concentration. The frequency and percentage of participants with positive and 
negative results will be summarized for each assessment time and overall for each 
participant by dose cohort. The detailed information will be included in the RAP. 
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12.4.7. 
Other Analyses 
All other exploratory analyses will be described in the RAP. 
12.4.8. 
Interim Analyses 
12.4.8.1. 
Arm A – belantamab mafodotin with Len/Dex 
Part 1 
During dose escalation, no formal interim analysis will be performed. Data will be 
reviewed through data visualization tool to inform dose escalation decisions. The mTPI 
design will be utilized to guide dose escalation/de-escalation decisions. More details of 
the dose escalation procedure are described in Section 6.1.1.1. 
Part 2 
Continuous monitoring will be conducted for Part 2 starting from when 5 participants are 
dosed at each dose level within each arm. The observed number of participants 
permanently discontinuing study treatment within the first two cycles due to AE related 
to belantamab mafodotin will be compared against the safety stopping rule in Table 30. 
Enrollment may stop if the safety stopping rule is met based on totality of safety data. For 
example, if 4 or more out of 5 participants permanently discontinued study treatment 
within the first 2 cycles due to AE related to belantamab mafodotin, enrollment may stop 
after review of all safety data; otherwise enrollment will continue. Operating 
characteristics for the stopping rule are provided in Appendix 11. 
Table 30 
Safety Stopping Rules for Arm A Part 2  
Number of dosed participants 
Stop if number of participants 
discontinuing study treatment 
within the first two cycles due 
to AE related to belantamab 
mafodotin is larger or equal to 
this this number 
Observed rate 
5-8 
4 
0.5-0.8 
9-12 
5 
0.42-0.56 
An interim analysis may be conducted when the last participant within each arm is 
followed for at least 1 cycle to evaluate safety, efficacy and PK profiles at each dose 
level. Following the interim analysis, additional analyses may be performed to continue 
to evaluate safety, efficacy and PK profiles at each dose level, prior to the final analyses. 
If any dose level is not enrolled due to safety concerns, it will not be included in the 
interim or final analyses. Additionally, if enrollment is stopped within a dose group, data 
may be analyzed for participants within the dose group who take at least 1 dose of any 
study treatment.  


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12.4.8.2. 
Arm B – belantamab mafodotin with Bor/Dex 
Part 1 
During dose escalation, no formal interim analysis will be performed. Data will be 
reviewed through the data visualization tool to inform dose escalation decisions. The 
mTPI design will be utilized to guide dose escalation/de-escalation decisions. More 
details of the dose escalation procedure are described in Section 6.1.2. 
Part 2 
Continuous monitoring will be conducted for Part 2 starting from when 5 participants are 
dosed at each dose level within each arm. The observed number of participants 
permanently discontinuing study treatment within the first two cycles due to AE related 
to belantamab mafodotin will be compared against the safety stopping rule in Table 31. 
Enrollment may stop if the safety stopping rule is met based on totality of safety data. For 
example, if 4 or more out of 5 participants permanently discontinued study treatment 
within the first 2 cycles due to AE related to belantamab mafodotin, enrollment may stop 
after review of all safety data; otherwise enrollment will continue. Operating 
characteristics for the stopping rule are provided in Appendix 11. 
Table 31 
Safety Stopping Rules for Arm B Part 2 
Number of dosed participants 
Stop if number of participants 
discontinuing study treatment 
within the first two cycles due 
to AE related to belantamab 
mafodotin is larger or equal to 
this this number 
Observed rate  
5-8 
4 
0.5-0.8 
9-12 
5 
0.42-0.56 
 
An interim analysis may be conducted when the last participant within each arm is 
followed for at least 1 cycle to evaluate safety, efficacy and PK profiles at each dose 
level. Following the interim analysis, additional analyses may be performed to continue 
to evaluate safety, efficacy and PK profiles at each dose level, prior to the final analyses. 
If any dose level is not enrolled due to safety concerns, it will not be included in the 
interim or final analyses. Additionally, if enrollment is stopped within a dose group, data 
may be analyzed for participants within the dose group who take at least 1 dose of any 
study treatment. 
12.4.9. 
Final Analysis 
Final analysis of the data captured in Part 1 and Part 2 for both Arm A and Arm B will be 
undertaken following 12 months post LSFD. (Section 6.3). Within each arm, data from 
the two parts may be combined for some analyses at the final analysis, as appropriate. 


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improvement in survival in multiple myeloma: changes in early mortality and outcomes 
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progression and survival in multiple myeloma relapsing after therapy with ImiDs and 
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Gamma-secretase directly sheds the survival receptor BCMA from plasma cells. Nat 
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CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 
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multiple myeloma. Leukemia. 2014;28:258-268. 
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therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621-631. 
Lonial S, Lee H C, Badros A, Trudel S, Nooka A K, Chari A, Abdallah A-O, et al. 
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two-arm, randomised, open-label, phase 2 study. Lancet Oncology, 2019, e-pub ahead of 
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for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomized, 
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Montes De Oca R, Bhattacharya S, Vitali N, et al. The anti-BCMA antibody-drug 
conjugate GSK2857916 drives immunogenic cell death and immune-mediated anti-tumor 
responses, and in combination with an OX40 agonist potentiates in vivo activity. 
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14. 
APPENDICES 
14.1. 
Appendix 1: Abbreviations and Trademarks 
14.1.1. 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
NONE 
 
MedDRA 
 
 
REVLIMID 
 
 
VELCADE 
 
14.1.2. 
Abbreviations and Acronyms 
Acronym 
Definition 
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 
ALT 
Alanine aminotransferase 
AMD 
Age-related macular degeneration 
ANC 
Absolute neutrophil count 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration time curve 
BCMA 
B-cell maturation antigen 
BCVA 
Best-corrected visual acuity 
BIB 
Bioanalysis, immunogenicity and biomarkers 
BID 
Twice daily 
BOR 
Bortezomib 
BM 
Bone marrow 
BMI 
Body mass index 
BSA 
Body surface area 
BW 
Body weight 
C1D1 
Cycle 1 Day 1 
CBC 
Complete blood count 
CIOMS 
Council for International Organizations of Medical Sciences 
CK 
Creatine kinase 
Cmax 
Maximum plasma concentration 
CONSORT 
Consolidated Standards of Reporting Trials 
CR 
Complete Response 
CRF 
Case Report Form 
CRP 
C-reactive protein 
CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CCI
CCI


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Acronym 
Definition 
CV 
Cardiovascular 
DCO 
Data cut-off 
Dex 
Dexamethasone 
DILI 
Drug-Induced Liver Injury 
DLT 
Dose-limiting toxicities 
DVT 
Deep vein thrombosis 
EC 
Ethics committee 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Report Form 
eGFR 
Estimated glomerular filtration rate 
EOI 
End of infusion 
EOS 
End of study 
EOT 
End of Treatment 
FDA 
Food and Drug Administration 
FISH 
Fluorescence-in-situ hybridization 
FLC 
Free light chain 
FSH 
Follicle-stimulating hormone 
FTIH 
First–Time-in-Human 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GVHD 
Graft-versus-host disease 
GSK 
GlaxoSmithKline 
HbsAg 
hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
HRT 
Hormone replacement therapy 
HSCT 
Hematopoietic stem cell transplant 
IB 
Investigator’s Brochure 
ICD 
immunogenic cell death 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use   
IHC 
Immunohistochemistry 
IMID 
Immunomodulatory drugs 
IMP 
Investigational Medicinal Product 
IMWG 
International Myeloma Working Group 
INR 
International normalization ratio 
IRB 
Institutional Review Board 
IRR 
Infusion-related reaction 
LDH 
Lactate dehydrogenase 
LEN 
Lenalidomide 
LLN 
Lower limit of normal 
LSFD 
Last subject first dose 
LSFV 
Last subject first visit 
LVEF 
Left ventricular ejection fraction 
MDRD 
Modified Diet in Renal Disease 
CCI


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Acronym 
Definition 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Myocardial infarction 
MM 
Multiple myeloma 
MMAF 
Monomethyl auristatin-F 
MoA 
Mechanism of action 
MR 
Minimal Response 
MSDS 
Material Safety Data Sheet 
MTD 
Maximum tolerated dose 
mTPI 
modified Toxicity Probability Interval 
NCCN 
National Comprehensive Cancer Network 
NCI 
National Cancer Institute 
NOS 
Not otherwise specified 
NYHA 
New York Heart Association 
ORR 
Overall Response Rate 
OSDI 
Ocular Surface Disease Index 
PACT 
Post analysis continued treatment 
PCR 
Polymerase chain reaction 
PD 
Progressive Disease 
PE 
Pulmonary embolism 
PET 
Positron Emission Tomography 
PI 
Proteasome inhibitors 
PK 
Pharmacokinetic(s) 
PO 
Per os (oral) 
PR 
Partial Response 
PRO 
Patient-Reported Outcome 
PRES 
Posterior Reversible Encephalopathy Syndrome 
QD 
Once daily 
QID 
Four times daily 
QoL 
Quality of life 
RAP 
Reporting and Analysis Plan 
RBC 
Red blood cell 
RP2D 
Recommended Phase 2 dose 
RPLS 
Reversible Posterior Leukoencephalopathy Syndrome 
RRMM 
Relapsed/Refractory Multiple Myeloma 
SAE 
Serious adverse event 
SC 
Subcutaneous 
sCR 
stringent Complete Response 
SCT 
Stem cell transplant 
SD 
Standard deviation of the mean 
S/D 
Step-down dosing 
SoA 
Schedule of Activities 
SoC 
Standard of Care 
SOI 
Start of infusion 
SPEP 
Serum Protein Electrophoresis 
SPM 
Second Primary Malignancies 
SRM 
Study Reference Manual 
CCI
CCI
CCI


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Acronym 
Definition 
t1/2  
Serum half-life 
TLS 
Tumor lysis syndrome 
tmax 
Time to maximum plasma concentration 
TNF 
Tumor necrosis factor 
TTP 
Time to Disease Progression 
ULN 
Upper limit of normal 
UPEP 
Urine protein electrophoresis 
VGPR 
Very good partial response 
VZIG 
Varicella zoster immune globulin 
WBC 
White blood cell 
WFI 
Water for injection 
WOCBP 
Woman of child-bearing potential 
 
CCI
CCI


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14.2. 
Appendix 2:  Study Governance Considerations and 
Informed Consent Process 
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 international council for harmonization of technical requirements for 
pharmaceuticals for human use (ICH) Good Clinical Practice (GCP) Guidelines 
• 
Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant 
documents (e.g., advertisements) must be submitted to an IRB/IEC by the 
Investigator and reviewed and approved by the IRB/IEC before the study is initiated.  
• 
Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants.  
• 
The investigator will be responsible for the following: 
• 
Providing written summaries of the status of the study to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/EC 
• 
Notifying the IRB/IEC of SAE or other significant safety findings as required by 
IRB/IEC procedures 
• 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations 
Financial Disclosure 
Investigators and sub-investigators will provide the Sponsor with sufficient, accurate 
financial information as requested to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
Informed Consent Process 
• 
The Investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions 
regarding the study.  
• 
Participants must be informed that their participation is voluntary.  Participants or 
their legally authorized representative will be required to sign a statement of 


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informed consent that meets the requirements of 21 CFR 50, local regulations, ICH 
guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center.  
• 
The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s) during 
their participation in the study.  
• 
A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorized representative.  
• 
Participants who are rescreened are required to sign a new ICF. 
The ICF may contain a separate section that addresses the use of remaining mandatory 
samples for optional exploratory research in accordance with SOP-GSKF-410. The 
investigator or authorized designee will explain to each participant the objectives of the 
exploratory research. Participants will be told that they are free to refuse to participate 
and may withdraw their consent at any time and for any reason during the storage period. 
A separate signature will be required to document a participant's agreement to allow any 
remaining specimens to be used for exploratory research.  Participants who decline to 
participate will not provide this separate signature. 
Data Protection 
• 
Participants will be assigned a unique identifier by the Sponsor.  Any participant 
records or datasets that are transferred to the Sponsor will contain the identifier only; 
participant names or any information which would make the participant identifiable 
will not be transferred.  
• 
The participant must be informed that his/her personal study-related data will be 
used by the Sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant.  
• 
The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
Committees Structure 
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 


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support publication of multicenter studies only in their entirety and not as individual 
site data. In this case, a coordinating investigator will be designated by mutual 
agreement. 
• 
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
Dissemination of Clinical Study Data 
• 
Where required by applicable regulatory requirements, an Investigator signatory will 
be identified for the approval of the CSR.  The Investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK site or other mutually-
agreeable location. 
• 
GSK will also provide the investigator with the full summary of the study results.  
The investigator is encouraged to share the summary results with the study 
participants, as appropriate. 
• 
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK Policy. 
• 
A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the Sponsor or designee electronically (e.g., laboratory 
data).  The investigator is responsible for verifying that data entries are accurate and 
correct by physically or electronically signing the CRF.  
• 
The investigator must maintain accurate documentation (source data) that supports 
the information entered in the CRF.  
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.  
• 
The Sponsor or designee is responsible for the data management of this study 
including quality checking of the data.  
• 
Study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and 
verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently 
approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements.  
• 
Records and documents, including signed ICF, pertaining to the conduct of this study 
must be retained by the investigator for 25 years from the issue of the final 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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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 the SRM. 
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 


T M F -1 4 6 2 4 3 5 8  
C O N FI D E N TI A L  
 
 
2 0 7 4 9 7  
 
Pr ot o c ol A m d 0 4  
 
1 9 5  
 
Ok e n, M. M., Cr e ec h, R. H., T or m ey, D. C., H ort o n, J., D avis, T. E., Mc F a d d e n, E. T., C ar b o n e, P. P.: T oxicity An d 
R es p o ns e Crit eri a Of T h e E ast er n C o o p er ativ e O nc ol o gy Gr o u p. A m J Cli n O nc ol 1 9 8 2; 5: 6 4 9 -6 5 5, [ Ok e n , 1 9 8 2] 
 
C CI - T hi s s e cti o n c o nt ai n e d Cli ni c al O ut c o m e A s s e s s m e nt d at a c oll e cti o n q u e sti o n n air e s or i n di c e s, w hi c h ar e pr ot e ct e d b y t hir d 
p art y c o p yri g ht l a w s a n d t h er ef or e h a v e b e e n e x cl u d e d.


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14.4. 
Appendix 4:  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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14.5. 
Appendix 5: New York Heart Association Classification 
The New York Heart Association (NYHA) Functional Classification: Class I, II, III or IV 
Heart Failure [New York Heart Association, 1994] provides a simple way of classifying 
the extent of heart failure. It places participants in one of 4 categories based on the level 
of limitation experienced during physical activity: 
Class 
Symptoms 
Class I 
(Mild) 
No limitation of physical activity. Ordinary physical activity does not cause undue 
fatigue, palpitation or dyspnea (shortness of breath). 
Class II 
(Mild) 
Slight limitation of physical activity. Comfortable at rest, but ordinary physical 
activity results in fatigue, palpitation or dyspnea. 
Class III 
(Moderate) 
Marked limitation of physical activity. Comfortable at rest, but less than ordinary 
physical activity results in fatigue, palpitation or dyspnea. 
Class IV 
(Severe) 
Unable to carry out any physical activity without discomfort. Symptoms of cardiac 
insufficiency at rest. If any physical activity is undertaken, discomfort is increased. 
The Criteria Committee of the New York Heart Association (NYHA). 1994. Nomenclature and Criteria for Diagnosis of 
Diseases of the Heart and Great Vessels. 9th Ed. Boston, Mass: Little, Brown & Co.; 1994:253-256. 
 


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14.6. 
Appendix 6: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study treatment, whether or not considered 
related to the study treatment. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study treatment. 
 
Events Meeting the AE Definition  
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses must be reported regardless of sequelae. 
• 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not 
be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting 
from lack of efficacy will be reported as AE or SAE if they fulfill the definition of 
an AE or SAE.  
 


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


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A SAE is defined as any untoward medical occurrence that, at any dose: 
d. Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
e. 
Is a congenital anomaly/birth defect 
f. 
Other situations: 
• 
Medical or scientific judgment must be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events must 
usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
g. Is associated with liver injury and impaired liver function defined as: 
• 
ALT 3 x ULN and total bilirubin* 2 x ULN (>35% direct), or 
• 
ALT 3 x ULN and INR** >1.5 
* Serum bilirubin fractionation should be performed if testing is available; if 
unavailable, measure urinary bilirubin via dipstick.  If fractionation is unavailable and 
ALT 3 x ULN and total bilirubin 2 x ULN, then the event is still to be reported as an 
SAE. 
** INR testing not required per protocol and the threshold value does not apply to 
participants receiving anticoagulants.  If INR measurement is obtained, the value is to 
be recorded on the SAE form. 
h. Refer to Appendix 9, Section 14.9 for liver chemistry follow-up procedures. 
 


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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 
• 
Peripheral arterial thromboembolism 
• 
Deep venous thrombosis/pulmonary embolism 
•   Revascularization 
 
Recording AE and SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE information in the CRF. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK or designee in lieu of completion of the GSK /AE/SAE 
CRF page. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE. 


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Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
(aside from corneal events) during the study and assign it to 1 of the following 
categories:  
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic 
observations only; intervention not indicated. 
• Grade 2: Moderate; minimal, local or noninvasive intervention indicated; 
limiting age appropriate instrumental ADL*. 
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL**. 
• Grade 4: Life-threatening consequences; urgent intervention indicated. 
• Grade 5: Death related to AE. 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using 
the telephone, managing money, etc. 
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the 
toilet, taking medications, and not bedridden. 
Corneal events associated with belantamab mafodotin will be graded according to 
the grading scale provide in Appendix 8. 
 
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 


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Assessment of Causality 
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 h of receipt 
of the information. 
 
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 h. 
• 
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 h 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 the SRM. 


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SAE Reporting to GSK via Paper CRF 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to the SAE coordinator. Details provided in the SRM. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time 
frames. 
• 
Contacts for SAE reporting can be found in the SRM. 
 


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14.7. 
Appendix 7: Contraceptive Guidance and Collection of 
Pregnancy Information 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other 
than the above, (e.g., Mullerian agenesis, androgen insensitivity), investigator 
discretion should be applied to determining study entry. 
Note:  Documentation can come from the site personnel’s: review of participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
• 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high follicle stimulating hormone (FSH) level in 
the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or hormonal replacement therapy 
(HRT). However, in the absence of 12 months of amenorrhea confirmation with 
more than one FSH measurement is required (in questionable cases a blood 
sample with simultaneous FSH >40 MIU/mL and estradiol <40 pg/mL 
[<147 pmol/L] is confirmatory).  
• 
Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen hormonal highly effective contraception methods if 
they wish to continue their HRT during the study.  Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment. 


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Contraception Guidance 
• 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 
• 
Highly Effective Methodsb That Have Low User Dependency  
• 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS)c 
• 
Bilateral tubal occlusion 
• 
Vasectomized partner 
• 
Note: Vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. Spermatogenesis cycle is approximately 90 days. 
• 
Highly Effective Methodsb That Are User Dependent 
• 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
• 
oral 
• 
intravaginal 
• 
transdermal 
• 
injectable 
• 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
• 
oral 
• 
injectable 
• 
Sexual abstinence 
• 
Note: Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with 
the study intervention. The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the study and the preferred and usual lifestyle of the 
participant. 
a. 
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
b. 
Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
c. 
Male condoms must be used in addition to hormonal contraception. If locally required, in accordance with 
Clinical Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive methods are limited to those 
which inhibit ovulation as the primary mode of action. 
 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhea method (LAM) are not acceptable methods of contraception for this 
study. Male condom and female condom should not be used together (due to risk of failure with friction). 


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Collection of Pregnancy Information 
Male participants with partners who become pregnant 
• 
Investigator will attempt to collect pregnancy information on the female partner of a 
male study participant who becomes pregnant while participating in this study. 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 h 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.  
• 
Information will be recorded on the appropriate form and submitted to GSK within 
24 h 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 6, Section 14.6.  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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14.8. 
Appendix 8: Corneal Event Grading and Mitigation Strategy 
Corneal events should be graded according to the guidelines provided in Table 33. 
In order to minimize the corneal findings, prophylactic preservative-free artificial tears 
should be administered in each eye at least 4 to 8 times daily, beginning on C1D1 until 
the End of Treatment (EOT). Allow at least 5-10 min between administration of artificial 
tears and steroid eye drops (if administered). In the event of ocular symptoms (i.e., dry 
eyes), the use of artificial tears may be increased up to every 2 h as needed. 
While not yet clinically demonstrated, it is theoretically possible that the application of a 
cooling eye mask during belantamab mafodotin administration, and in the first few hours 
after infusion may subsequently decrease ocular side effects. On the day of infusion, the 
following may be considered:  
• 
Beginning with the start of each belantamab mafodotin infusion, participants may 
apply cooling eye masks to their eyes for approximately 1 h or as much as tolerated 
by the participant.   
• 
Participants are encouraged to continue using the cooling eye mask beyond the first 
hour for up to 4 h. Further use beyond 4 h is at the participant’s discretion. 
Contact lenses are prohibited while the participant is on study treatment. 
The GSK grading scale for corneal events was developed to capture both corneal findings 
and visual acuity changes in participants treated with belantamab mafodotin and to 
provide recommendations for dosing decisions. This GSK scale is different from CTCAE 
criteria for eye disorders which relies mainly on participant’s symptoms and participant’s 
ability to attend to ‘activities of daily living’ and which (CTCAE) is to be used for 
grading of the adverse events.   
A summary of prophylactic interventions for corneal events associated with belantamab 
mafodotin is provided in Table 32. In addition to reporting eye disorders using CTCAE 
4.03 criteria, corneal events associated with belantamab mafodotin must also be graded 
according to the guidelines provided in Table 33. Additional guidance on visual acuity 
changes is provided in  Table 34. 
In the FTIH study (BMA117159), eye examinations showed that most participants 
continued to receive belantamab mafodotin dose when either a GSK Scale Grade 2 
corneal examination finding or a 2-3-line decrease in visual acuity was reported. With 
this dosing paradigm, participants generally showed improvement in both corneal 
examination findings and visual acuity over time. Therefore, the dosing guideline has 
been adjusted to allow dosing with belantamab mafodotin if only one component on the 
GSK corneal event scale indicates Grade 2 corneal event. 


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Table 32 
Prophylactic Measures for Corneal Events Associated with 
Belantamab Mafodotin 
Prophylactic 
Measurea 
Dose and Administration 
Timing 
Preservative-free 
artificial tears 
Administer in each eye at least 
4 to 8 times daily 
Administer daily beginning on Cycle 1 
Day 1 until EOT. Allow 5-10 min 
between administration of artificial tears 
and steroid eye drops 
Cooling eye mask 
May apply cooling eye mask to 
both eyes for approximately 1 h 
or as much as tolerated  
During belantamab mafodotin infusion 
administration in the first hour for up to 
4 h, as tolerated 
a. 
Dose modifications and treatment for ocular toxicities are discussed in Section 8.2.1 
 
 


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Table 33 
Grading Scale for Corneal Events Associated with Belantamab Mafodotin 
Measure 
 
Grade 1 per GSK Scale  
Grade 2 per GSK Scale 
Grade 3 per GSK Scale 
Grade 4 per GSK Scale 
Ophthalmic exam 
findings 
Mild superficial keratopathy 
(change from baseline) 
 
Moderate punctate keratopathy 
and/or 
Mild/patchy microcysts 
and/or 
Mild/patchy Epithelial or stromal 
edema 
and/or 
Sub-epithelial haze (peripheral)  
and/or 
Active stromal opacity (peripheral) 
Severe punctate keratopathy 
and/or 
Diffuse microcysts 
and/or 
Diffuse Epithelial or stromal edema 
and/or 
Sub-epithelial haze (central)  
and/or 
Active stromal opacity (central) 
Corneal ulcer 
Visual Acuity b, c 
Change of 1 line from baseline Change of 2-3 lines from baseline and 
not worse than 20/200b 
Change of more than 3 lines from 
baseline and not worse than 20/200b 
 
Worse than Vision 20/200b 
 
Note: Standardized guidance for grading ophthalmic findings associated with belantamab mafodotin is provided to sites in the ophthalmology SRM. Ophthalmic exam findings as 
described must be present in a participant to utilize GSK’s scale.  
a. 
Grading is based on most severe finding. If eyes differ in severity, GSK grading should be based on the more severe eye. 
b. 
Change in visual acuity should be due to corneal events. If change in vision is for reason other than corneal events, ophthalmic exam findings will drive event grading.  
c. 
See  Table 34 for additional guidance on how to grade changes in visual acuity depending on baseline vision. If a participant has a baseline visual acuity of 20/200 or worse in an 
eye, ophthalmic exam findings will drive event grading. 
 


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 Table 34 
Guidance for Assessing Changes in Visual Acuity for GSK 
Grading Scale 
Baseline Vision 
(best corrected) 
Grade 1 per 
GSK scale 
Grade 2 per GSK scale 
Grade 3 per 
GSK scale 
Grade 4 per GSK 
scale 
20/15 to 20/16 
From -0.12 to -0.1 
20/20 
0 
20/25 to 20/30 or 20/32 
0.1 to 0.18 or 0.2 
20/40 to 20/200 
0.3 to 1.0 
Worse than 20/200 
>1.0 
20/20 
0 
20/25 
0.1  
20/30 to 20/40  
0.18 to 0.3 
20/50 to 20/200 
0.4 to 1.0  
Worse than 20/200 
>1.0 
20/25 
0.1 
20/30 to 20/32 
0.18 to 0.2 
20/40 to 20/50 
0.3 to 0.4  
20/60 to 20/200 
0.48 to 1.0  
Worse than 20/200 
>1.0  
20/30 to 20/32 
0.18 to 0.2 
20/40 
0.3  
20/50 to 20/60 or 20/63 
0.4 to 0.48 or 0.5 
20/70 to 20/200 
0.56 to 1.0 
Worse than 20/200 
>1.0 
20/40 
0.3 
20/50 
0.4  
20/60 to 20/70 or 20/80 
0.48 to 0.56 or 0.6 
20/100 to 20/200 
0.7 to 1.0  
Worse than 20/200 
>1.0 
20/50 
0.4 
20/60 to 20/63 
0.48 to 0.5  
20/70 to 20/100 
0.56 to 0.7  
20/125 to 20/200 
0.8 to 1.0  
Worse than 20/200 
>1.0  
20/60 to 20/63 
0.48 to 0.5 
20/70 to 20/80 
0.56 to 0.6  
20/100 to 20/125 
0.7 to 0.8 
20/150 to 20/200 
0.88 to 1.0 
Worse than 20/200 
>1.0  
20/70 to 20/80 
0.56 to 0.6 
20/100 
0.7  
20/125 to 20/150 or 
20/1600.8 to 0.88 or 0.9 
20/200  
1.0  
Worse than 20/200 
>1.0 
20/100 
0.7 
20/125 
0.8  
20/150 to 20/160 or 
20/2000.88 to 0.9 or 1.0 
N/A 
Worse than 20/200 
>1.0  
20/125 
0.8 
20/150 to 20/160 
0.88 to 0.9 
20/200  
1.0  
N/A 
Worse than 20/200  
>1.0  
20/150 to 20/160 
0.88 to 0.9 
20/200 
1.0  
N/A 
N/A 
Worse than 20/200 
>1.0  
Worse than 
20/160 
>/= 1.0 
N/A 
N/A 
N/A 
Any further 
reduction from 
baseline is 
considered Grade 4 
Note: The Visual acuity is presented as Snellen equivalent and logMAR value. 


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14.9. 
Appendix 9: Liver Safety: Required Actions, Follow-up 
Assessments, and Study Treatment Rechallenge Guidelines 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology. 
Liver Chemistry Stopping Criteria – Liver Stopping Event 
ALT-absolute 
ALT 5 x ULN 
ALT Increase 
ALT 3 x ULN persists for 4 weeks 
Bilirubin1, 2 
ALT 3 x ULN and total bilirubin 2 x ULN (>35% direct bilirubin)  
INR2  
ALT 3 x ULN and INR >1.5 
Cannot Monitor 
ALT 3 x ULN and cannot be monitored weekly for 4 weeks 
Symptomatic3 
ALT 3 x ULN 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 treatment  
• 
Report the event to GSK within 24 h 
• 
Complete the liver event form and complete 
an SAE data collection tool if the event also 
meets the criteria for an SAE2 
• 
Perform liver event follow up assessments as 
described in the Follow Up Assessment 
column 
• 
Monitor the participant until liver chemistries 
resolve, stabilize, or return to within baseline 
(see MONITORING below) 
MONITORING: 
If ALT≥3xULN AND total bilirubin  2xULN 
or INR >1.5: 
• 
Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, total bilirubin and INR) 
and perform liver event follow up 
assessments within 24 h 
• 
Monitor participants twice weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
• 
Viral hepatitis serology4 
• 
Obtain INR and recheck with each liver chemistry 
assessment until the transaminase values show 
downward trend 
• 
Blood sample for pharmacokinetic (PK) analysis of 
belantamab mafodotin and a blood sample for 
, obtained within 70 days after last dose5 
• 
Serum creatine phosphokinase (CPK) and lactate 
dehydrogenase (LDH), gamma glutamyl 
transferase [GGT], glutamate dehydrogenase 
[GLDH], and serum albumin. 
• 
Fractionate bilirubin, if total bilirubin 2 x ULN 
• 
Obtain complete blood count with differential to 
assess eosinophilia 
• 
Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity, on the 
liver report form 
• 
Record use of concomitant medications on the 
concomitant medications report form including 
acetaminophen, herbal remedies, other over the 
counter medications 
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• 
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 INR) and 
perform liver event follow up assessments 
within 24-72 hours 
• 
Monitor participants weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
RESTART/RECHALLENGE 
• 
Restart/rechallenge is allowed per 
protocol but do not resume study 
intervention unless GSK approval is 
granted; If restart/rechallenge is not 
granted, permanently discontinue study 
intervention and continue participant in the 
study for any protocol specified follow up 
assessments. Refer to Restart/Rechallenge 
guidelines in Appendix 9 Section 14.9 
• 
Record alcohol use on the liver event alcohol 
intake form 
If ALT 3xULN AND total bilirubin 2xULN or 
INR >1.5 obtain the following in addition to the 
assessments listed above:: 
• 
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 
computerized tomography) and /or liver biopsy to 
evaluate liver disease; complete Liver Imaging 
and/or Liver Biopsy 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 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 3 x ULN and bilirubin 2 x ULN.  
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 3 x ULN and total bilirubin 2 x ULN (>35% direct bilirubin) or ALT 3 x ULN and INR >1.5, 
which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE; the INR threshold 
value 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. 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]. 
5. Record the date/time of the PK/
 blood sample draw and the date/time of the last dose of study treatment 
prior to blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK/
 sample cannot be 
collected in the time period indicated above, do not obtain a PK/
 sample. Instructions for sample handling 
and shipping are in the SRM.  
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Liver Chemistry Increased Monitoring Criteria and Actions with Continued Study 
Intervention Liver Monitoring Event 
Criteria 
Actions 
ALT 3 x ULN but <5 x ULN and  total 
bilirubin <2 x ULN or INR 1.5, without 
symptoms believed to be related to liver injury 
or hypersensitivity and who can be monitored 
weekly for 4 weeks 
 
• 
Notify the GSK medical monitor within 24 h of 
learning of the abnormality to discuss participant 
safety.  
• 
Participant can continue study treatment   
• 
Participant must return weekly for repeat liver 
chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) until they resolve, stabilize or return to 
within baseline  
• 
If at any time participant meets the liver chemistry 
stopping criteria, proceed as described above 
• 
If, after 4 weeks of monitoring, ALT <3 x ULN and 
bilirubin <2 x ULN, monitor participants twice 
monthly until liver chemistries normalize or return 
to within baseline. 
 
14.9.1. 
Liver Safety Drug Restart or Re-Challenge Guidelines 
A participant who met liver chemistry stopping criteria cannot resume study treatment 
unless all of the following conditions are met: 
• 
GSK approval is granted (as described below), 
• 
Institutional Review Board/Independent Ethics Committee (IRB/IEC) approval is 
obtained, and 
• 
Separate ICF for study treatment restart/rechallenge is signed by the participant and 
the participant is informed of any associated risks. 
If GSK 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. 
14.9.1.1. 
Rechallenge Following Liver Stopping Events that are Possibly Related 
to Study Treatment 
Following drug-induced liver injury, drug rechallenge is associated with a 13% 
mortality across all drugs in prospective studies [Andrade, 2009]. Clinical outcomes 
vary by drug, with nearly 50% fatality with halothane readministered within one month 
of initial injury. However, some drugs seldom result in recurrent liver injury or fatality.   
Risk factors for a fatal drug rechallenge outcome include: 
• 
Hypersensitivity with initial liver injury (e.g., fever, rash, eosinophilia)  


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• 
Jaundice or bilirubin >2 x ULN with initial liver injury (direct bilirubin >35% of 
total) 
• 
Ongoing severe liver injury defined by: ALT ≥3 × ULN, bilirubin ≥2 × ULN 
(direct bilirubin >35% of total), or INR ≥1.5 
• 
SAEs or fatality has earlier been observed with drug rechallenges [Hunt, 2010; 
Papay, 2009]. 
• 
Evidence of drug-related preclinical liability (e.g. reactive metabolites; 
mitochondrial impairment) 
Rechallenge refers to resuming study treatment following study treatment induced liver 
injury (DILI). Because of the risks associated with rechallenge after DILI, this should 
only be considered for a participant for whom there is compelling evidence of benefit 
from a critical or life-saving medicine, there is no alternative approved medicine 
available, and a benefit:risk assessment of rechallenge is considered to be favorable. 
Approval by GSK for rechallenge with study treatment can be considered where: 
• 
The Principal Investigator (PI) requests consideration of rechallenge with study 
treatment for a participant who is receiving compelling benefit with study treatment 
that exceeds risk, and no effective alternative therapy is available.   
• 
IRB/IEC approval for rechallenge with study treatment must be obtained. 
If the rechallenge is approved by GSK in writing: 
• 
The participant must be provided with a clear description of the possible benefits and 
risks of study treatment administration, including the possibility of recurrent, more 
severe liver injury or death.   
• 
The participant must also provide signed informed consent specifically for the 
rechallenge with study treatment.  Documentation of informed consent must be 
recorded in the study file. 
• 
Study treatment must be administered at the dose specified by GSK. 
• 
Participants approved by GSK for rechallenge with study treatment must return to 
the clinic twice a week for liver chemistry tests until stable liver chemistries have 
been demonstrated and then standard laboratory monitoring may resume as per 
protocol. 
• 
If after study treatment rechallenge, participant meets protocol-defined liver 
chemistry stopping criteria, study treatment should be permanently discontinued.  
• 
GSK Medical Monitor, and the IRB/IEC as required, must be informed of the 
participant’s outcome following study treatment rechallenge.  
• 
GSK to be notified of any adverse events, as per Section 10.2.4 and Appendix 6 
(Section 14.6).  


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14.9.1.2. 
Restart Following Transient Resolving Liver Stopping Events NOT 
Related to Study Treatment 
Restart refers to resuming study treatment following liver stopping events in which there 
is a clear underlying cause (other than DILI) of the liver event (e.g., biliary obstruction, 
pancreatic events, hypotension, acute viral hepatitis). Furthermore, restart is not permitted 
following liver stopping event when the underlying cause was alcohol-related hepatitis. 
Approval by GSK for study treatment restart can be considered where: 
• 
Principle Investigator requests consideration for study treatment restart if liver 
chemistries have a clear underlying cause (e.g., biliary obstruction, hypotension and 
liver chemistries have improved to normal or are within 1.5 x baseline and ALT 
<3 x ULN). 
• 
Possible study treatment-induced liver injury has been excluded by the principle 
investigator and the study team. This includes the absence of markers of 
hypersensitivity (otherwise unexplained fever, rash, eosinophilia). Where a study 
treatment has an identified genetic marker associated with liver injury (e.g. lapatinib, 
abacavir, amoxicillin/clavulanate), the presence of the marker should be excluded. If 
study treatment-related liver injury cannot be excluded, the guidance on rechallenge 
as stated in previous section will apply. 
• 
There is no evidence of alcoholic hepatitis. 
• 
IRB/IEC approval of study treatment restart must be obtained, as required. 
If restart of study treatment is approved by GSK in writing: 
• 
The participant must be provided with a clear description of the possible benefits and 
risks of study treatment administration, including the possibility of recurrent, more 
severe liver injury or death. 
• 
The participant must also provide signed informed consent specifically for the study 
treatment restart.  Documentation of informed consent must be recorded in the study 
file. 
• 
Study treatment must be administered at the dose specified by GSK. 
• 
Participants approved by GSK for restart of study treatment must return to the clinic 
once a week for liver chemistry tests until stable liver chemistries have been 
demonstrated and then laboratory monitoring may resume as per protocol.  
• 
If participant meets protocol-defined liver chemistry stopping criteria after study 
treatment restart, study treatment should be permanently discontinued. 
• 
GSK Medical Monitor, and the IRB/IEC must be informed of the participant’s 
outcome following study treatment restart.  
• 
GSK to be notified of any adverse events, as per Section 10.2.4. 
 


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14.9.1.3. 
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 et al. 
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 et al.  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;43:2363–2369 
Papay JI, Clines D, Rafi R, Yuen N, Britt SD, Walsh JS et al. Drug-induced liver injury 
following positive drug rechallenge.  Regul Tox Pharm. 2009;54:84-90.  
 
 


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14.10. 
Appendix 10:  Genetics 
Naturally occurring genetic variation may contribute to inter-individual variability in 
response to medicines, as well as an individual's risk of developing specific diseases.  
Genetic factors associated with disease characteristics may also be associated with 
response to therapy, and could help to explain some clinical study outcomes. For 
example, genetic variants associated with age-related macular degeneration (AMD) are 
reported to account for much of the risk for the condition [Gorin, 2012] with certain 
variants reported to influence treatment response [Chen, 2012]. Thus, knowledge of the 
genetic etiology of disease may better inform understanding of disease and the 
development of medicines. Additionally, genetic variability may impact the 
pharmacokinetics (absorption, distribution, metabolism, and elimination), or 
pharmacodynamics (relationship between concentration and pharmacologic effects or the 
time course of pharmacologic effects) of a specific medicine and/or clinical outcomes 
(efficacy and/or safety) observed in a clinical study. 
Therefore, where local regulations and IRB/IEC allow, a blood sample will be collected 
for DNA analysis. 
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14.10.2. 
Study Population 
Any participant who is enrolled in the study can participate in genetic research.  
Participant participation in the genetic research is voluntary and refusal to participate will 
not indicate withdrawal from the clinical study. Refusal to participate will involve no 
penalty or loss of benefits to which the participant would otherwise be entitled. 
14.10.3. 
Study Assessments and Procedures 
A key component of successful genetic research is the collection of samples during 
clinical studies. Collection of samples, even when no a priori hypothesis has been 
identified, may enable future genetic analyses to be conducted to help understand 
variability in disease and medicine response. 
• 
A 6 mL blood sample will be taken for Deoxyribonucleic acid (DNA) extraction. 
A blood sample is collected at the baseline visit, after the participant has been provided 
informed consent for genetic research. Instructions for collection and shipping of the 
genetic sample are described in the laboratory manual. The DNA from the blood sample 
may undergo quality control analyses to confirm the integrity of the sample.  If there are 
concerns regarding the quality of the sample, then the sample may be destroyed. The 
blood sample is taken on a single occasion unless a duplicate sample is required due to an 
inability to utilize the original sample. 
The genetic sample is labelled (or “coded”) with the same study-specific number used to 
label other samples and data in the study. This number can be traced or linked back to the 
participant by the Investigator or site staff. Coded samples do not carry personal 
identifiers (such as name or social security number). 
Samples will be stored securely and may be kept for up to 15 years after the last 
participant completes the study, or GSK may destroy the samples sooner. GSK or those 
working with GSK (for example, other researchers) will only use samples collected from 
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the study for the purpose stated in this protocol and in the ICF. Samples may be used as 
part of the development of a companion diagnostic to support the GSK medicinal 
product. 
Participants can request their sample to be destroyed at any time. 
14.10.4. 
Informed Consent 
Participants who do not wish to participate in the genetic research may still participate in 
the study. Genetic informed consent must be obtained prior to any blood being taken.  
14.10.5. 
Participant Withdrawal from Study 
If a participant who has consented to participate in genetic research withdraws from the 
clinical study for any reason other than being lost to Follow-up, the participant will be 
given a choice of one of the following options concerning the genetic sample, if already 
collected: 
• 
Continue to participate in the genetic research in which case the genetic DNA sample 
is retained 
• 
Discontinue participation in the genetic research and destroy the genetic DNA 
sample 
If a participant withdraws consent for genetic research or requests sample destruction for 
any reason, the investigator must complete the appropriate documentation to request 
sample destruction within the timeframe specified by GSK and maintain the 
documentation in the site study records. 
Genotype data may be generated during the study or after completion of the study and 
may be analyzed during the study or stored for future analysis. 
• 
If a participant withdraws consent for genetic research and genotype data has not 
been analyzed, it will not be analyzed or used for future research. 
• 
Genetic data that has been analyzed at the time of withdrawn consent will continue 
to be stored and used, as appropriate. 
14.10.6. 
Screen and Baseline Failures 
If a sample for genetic research has been collected and it is determined that the 
participant does not meet the entry criteria for participation in the study, then the 
investigator should instruct the participant that their genetic sample will be destroyed.  
No forms are required to complete this process as it will be completed as part of the 
consent and sample reconciliation process. In this instance a sample destruction form will 
not be available to include in the site files. 
14.10.7. 
Provision of Study Results and Confidentiality of Participant’s 
Genetic Data 
GSK may summarize the genetic research results in the CSR, or separately and may 
publish the results in scientific journals. 


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GSK may share genetic research data with other scientists to further scientific 
understanding in alignment with the informed consent. GSK does not inform the 
participant, family members, insurers, or employers of individual genotyping results that 
are not known to be relevant to the participant’s medical care at the time of the study, 
unless required by law. This is due to the fact that the information generated from genetic 
studies is generally preliminary in nature, and therefore the significance and scientific 
validity of the results are undetermined. Further, data generated in a research laboratory 
may not meet regulatory requirements for inclusion in clinical care. 
14.10.8. 
Germline Control 
US Food and Drug Administration states that an in vitro companion diagnostic device 
(IVD) could be essential for the safe and effective use of a corresponding therapeutic 
product to: 
• 
Identify participants who are most likely to benefit from a particular therapeutic 
product; 
• 
Identify participants likely to be at increased risk for serious adverse reactions as a 
result of treatment with a particular therapeutic product; 
• 
Monitor response to treatment for the purpose of adjusting treatment (e.g., schedule, 
dose, discontinuation) to achieve improved safety or effectiveness; 
• 
Identify participants in the population for whom the therapeutic product has been 
adequately studied, and found safe and effective, i.e., there is insufficient 
information about the safety and effectiveness of the therapeutic product in any other 
population. 
Global regulatory requirements for IVD companion diagnostic tests are evolving.  If a 
DNA-based IVD companion diagnostic device might be needed to identify participants 
who are appropriate for the GSK medicinal product(s) under investigation in this 
protocol, then GSK should collect and retain DNA samples from participants who carry 
the genetic variant of interest as well as DNA samples from participants who do not carry 
the genetic variants of interest to validate the performance of the companion diagnostic.  .  
Therefore, where local regulations and IRB/IEC allow, a sample will be collected for 
DNA analysis.   Any IVD companion diagnostic research objectives should be described 
in participant ICFs. 
14.10.9. 
References 
Chen H, Yu KD, Xu GZ. Association between Variant Y402H in Age-Related Macular 
Degeneration (AMD) Susceptibility Gene CFH and Treatment Response of AMD: A 
Meta-Analysis. PloS ONE. 2012;7:e42464 
Gorin MB. Genetic insights into age-related macular degeneration: Controversies 
addressing risk, causality, and therapeutics. Mol. Asp. Med. 2012;33:467-486. 


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14.11. 
Appendix 11: Operating Characteristics of Safety Stopping 
Rule for Expansion Cohort 
 


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14.12. 
Appendix 12: 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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14.13. 
Appendix 13: Alternative Health Care Approaches 
Home Healthcare (General Visit) 
Where applicable country, local regulations and infrastructure allow, home healthcare 
may be permitted.  Home healthcare is defined as a remote visit(s) that is/are performed 
at the participant’s home by qualified personnel (e.g. nurse practitioner, physician’s 
assistant).  Please refer to SRM for additional details. 
Activities that may be done as part of a home healthcare visit will follow the schedule 
provided in the SoA (Section 3) and could include:  
• 
Collection of blood and urine samples including:  
• 
Safety assessments which may include routine blood and urine sampling 
• 
PK and ADA specimen collection 
• 
Efficacy assessments  
• 
Biomarker, immunogenicity and genetic assessments 
• 
Pregnancy tests 
• 
12-Lead ECG 
• 
Other assessments as clinically indicated 
Note:  Biological samples should not be collected if they cannot be processed in 
a timely manner or appropriately stored until their intended use. Please refer to 
the SRM/lab manual for sample collection and storage requirements. 
• 
Measurement of vital signs (BP, heart rate, body temperature) and weight. 
• 
Physical examination 
• 
Administration of study treatments (subcutaneous delivery only, no i.v. or infusions). 
• 
Administration of medication 
• 
Identification and reporting of concomitant medications. 
• 
Dosing diary review for medication compliance. 
• 
Identification and reporting of AEs/SAEs. 
Note: The investigator or other qualified medical professional must ensure reporting 
of AEs and SAEs is completed in accordance with the protocol and applicable 
regulations and that the appropriate medical intervention, therapeutic intervention, 
and/or support measures are instituted, as necessary.  
The participant should be informed of any potential risks associated with Home 
Healthcare and sign a Informed Consent Form if required by local law or regulations. 
IRB/Ethics committee should be informed and/or approve of this change in approach and 
the process documented in study files. 


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Home Healthcare (Ophthalmologic Exam) 
Where applicable country and local regulations and infrastructure allow, protocol-
required eye exams may be done in the participant’s home or alternative location.  
Activities that may be done as part of remote eye exam must follow the schedule 
provided in the SoA (Section 3) and include (refer to SRM for additional details):  
• 
Visual Acuity   
• 
Slit lamp exam  
• 
Ophthalmoscopy 
• 
Other assessments as clinically indicated 
The participant should be informed of any potential risks associated with Home 
Healthcare Ophthalmologic exams and sign a revised Informed Consent Form if required. 
IRB/Ethics committee should be informed if required and/or approve of this change in 
approach and the process documented in study files. 
Telemedicine 
Where applicable country and local regulations and infrastructure allow, telemedicine 
visits may be permitted.  Telemedicine visits are defined as online (virtual) visits which 
will use secure video conference, phone calls, a web portal and/or mobile application as a 
way of communicating with and monitoring the participant’s progress.  Telemedicine 
visits are conducted by an investigator, site staff or other qualified medical professionals 
and may be done in conjunction with visits from Home Healthcare personnel (see above). 
Refer to SRM for additional details. 
Activities that may be done as part of a telemedicine visit include: 
• 
Medical evaluation of the participant  
• 
Identification and reporting of concomitant medications. 
• 
Dosing diary review for medication compliance. 
• 
Identification, management, and reporting of AEs and SAEs.   
Note: The investigator, site staff or other qualified medical professional must ensure 
reporting of AEs and SAEs is completed in accordance with the protocol and 
applicable regulations and that the appropriate medical intervention, therapeutic 
intervention, and/or support measures are instituted, as necessary. Participants 
utilizing telemedicine can report AEs at any time via an app, phone call or 
videoconference with site staff. 
The participant should be informed of any potential risks associated with the virtual 
medium and sign a revised Informed Consent Form if required. IRB/Ethics committee 
should be informed if applicable and/or approve of this change in approach and the 
process documented in study files. 
 


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14.14. 
Appendix 14: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
14.14.1. 
Protocol Amendment 3 (13-Jul-2020)  
Amendment 3: 13-JUL-2020 
Where this Protocol Amendment applies: 
Protocol Amendment 3 applies to all participants in all countries and at all sites.  
Overall rationale for Amendment 3:  
Protocol Amendment 3 includes updated duration of contraception for female participants 
to align with this guidance of child bearing potential based on review of guidelines on 
aneugens. 
Additionally, upon review of safety data from Study 205678 (DREAMM-2), it was 
determined that ocular changes associated with belantamab mafodotin treatment were 
mostly limited to the corneal epithelium [GSK Document Number 2013N175128 V08, 
2020]. Therefore, further collection of ocular safety data in belantamab mafodotin studies 
will be focused on corneal changes. Review of this data also indicated that the use of 
corticosteroid eye drops was ineffective in preventing or mitigating changes to the 
corneal epithelium associated with belantamab mafodotin [Lonial, 2020]. The 
discontinuation of corticosteroid eye drops as prophylaxis was communicated to the sites 
via a Protocol clarification letter dated 21 October 2019. Protocol Amendment 3 includes 
changes to ophthalmologic assessments based on these findings.   
Preclinical data from xenograft mouse models and emerging clinical data from Arm A in 
Amendment 2 suggests greater activity of belantamab mafodotin in combination with 
lenalidomide. Given this, doses higher than 2.5 mg/kg of belantamab mafodotin will not 
be evaluated in combination with lenalidomide/ dexamethasone in Arm A in Amendment 
3.  
Furthermore, in order to reduce increased exposure of belantamab mafodotin over time 
and potentially improve the benefit/risk for participants, reduced dose levels and 
extended dosing schedules for belantamab mafodotin will be evaluated in Amendment 3.  
• Arm A (Belantamab mafodotin + Len/Dex; 28-day cycle): As per above, in 
Arm A Part 2, an alternate dosing schedule of STRETCH (Q8W) dosing may be 
explored for the 1.9 mg/kg dose level if emerging data (from either this study or 
across the program) suggests that this schedule may further optimize the 
tolerability or offers an improved benefit/risk profile. To enable this, a potential 
extended dosing schedule has been introduced via this amendment, where 
belantamab mafodotin at 1.9 mg/kg will be administered once every 8 weeks 
(STRETCH) and will be evaluated dependent on emerging data. The cycle 


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duration will remain 28 days/4 weeks. Up to 12 participants will be enrolled in 
this new cohort. 
• Arm B (Belantamab mafodotin + Bor/Dex; 21-day cycle): Similarly, in Arm B 
Part 2, 2 new dosing schedules (STRETCH and Step-Down [S/D] STRETCH) 
and one new (reduced) dose level (dose level -1 at 1.9 mg/kg) of belantamab 
mafodotin has been added. In the extended dosing schedule, belantamab 
mafodotin will be administered every 6 weeks (STRETCH). The cycle duration 
will remain 21 days/3 weeks. Additionally, a S/D STRETCH schedule with a first 
dose of 2.5mg/kg dose at C1D1 followed by subsequent planned doses of 
1.9 mg/kg dose starting on Day 1 of alternate 21-day/3-week cycles C3 onwards 
(C3, C5, C7, and so on) will be evaluated. Furthermore, as target engagement and 
responses have been shown to occur at 1.9 mg/kg (and lower dose levels) in the 
first-time in human (FTIH) study BMA117159, belantamab mafodotin dose at a 
reduced dose level of 1.9 mg/kg in combination with SoC will be additionally 
explored in Arm B Part 2. To evaluate these additional dose levels and schedules, 
4 new dosing cohorts (2.5 mg/kg STRETCH, 2.5 → 1.9 mg/kg S/D STRETCH, 
1.9 mg/kg SINGLE (Q3W dosing) and 1.9 mg/kg STRETCH) are being added. 
Up to 12 participants will be enrolled in each of these 4 new cohorts. 
Protocol Amendment 3 includes the following: 
Section # and 
Name 
Description of Change 
Brief Rationale 
Belantamab Mafodotin Program Level Changes 
Section 1, Treatment 
Groups and 
Treatment Duration, 
Section 8.1.6.1 and 
Section 8.1.6.2 
Added “or end of study” to Arm A and 
Arm B text on continuing treatment until: 
“progressive disease (PD), intolerable 
AEs, consent withdrawal, or death” 
To make text consistent with 
Section 6.3 
Section 3, Table 4 
and Table 10 
Removed requirement for fasting 
glucose test at Screening. Fasting 
glucose and HbA1c to be done as 
clinically indicated and at End of 
Treatment 
Glucose included in chemistry panel 
and fasting glucose/HbA1c to be 
assessed as clinically indicated on-
treatment. 
Section 3, Table 4 – 
Table 8, Table 10, 
Section 10.6.10, and 
Table 27 
Removed troponin and B-type natriuretic 
peptide (BNP) testing.  
Based on clinical experience to date 
with belantamab mafodotin, and as 
reviewed by the GSK cardiac safety 
panel, it was agreed that troponin 
and B-type natriuretic peptide (BNP) 
was not required unless clinically 
indicated 
Section 3, Table 4 
Acceptable BM aspirate/biopsy changed 
from within 21 to within 28 days prior to 
first dose. 
Broaden window to avoid excessive 
procedures. 
Section 3, Table 5 - 
Table 8 
ECG footnote: timing for obtaining 
triplicate ECGs updated 
Broaden collection period for ease of 
use in clinic 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 3, Table 5 – 
Table 8 
PK blood sampling footnote: timing for 
obtaining EOI PK samples increased, 
language pertaining to collection 
following dosage delay clarified. 
Clarification; Broaden collection 
period for ease of use in clinic 
Section 3, Table 5 – 
Table 8, Table 10, 
Section 10.6.7 
Ocular exams: timing for on-study exams 
changed from every 4 weeks prior to Day 
1 dosing, to prior to belantamab 
mafodotin for the first 6 doses. Also 
changes to further exam schedule based 
on presence/absence of new corneal 
events.  
Ocular substudy safety data from 
Study 205678 data indicated that 
participant symptoms should 
determine the need for 
ophthalmology exams.  
 
Additional collection of digital 
photography is not needed based on 
sufficient collection of ocular 
photography in Study 205678. 
Section 3, Table 5 – 
Table 8; Section 
4.3.1; Section 14.8 
Corneal events management: removed 
text on prophylaxis with steroid eye 
drops.  
Steroid eye drops not beneficial in 
preventing or mitigating corneal 
events associated with belantamab 
mafodotin, based on findings from 
ocular substudy from Study 205678. 
Section 3, Table 5 – 
Table 8, and Section 
10.6.11 
Genetic sample: added text permitting 
recollection of genetic sample as 
necessary. 
Enables genetic testing to proceed if 
original sample is damaged, unable 
to be processed, or if insufficient 
DNA was extracted. 
Synopsis, Section 3 
Table 10, 
Section 4.3.1, 
Section 7.1, 
Section 7.3, 
Section 10.2.8 and 
Appendix 7 
Duration of contraception after last dose 
of belantamab mafodotin changed to 6 
months for males and 4 months for 
females 
Based on review of global guidelines 
on aneugens.  
Synopsis, Section 
4.2.3 
Updated description of belantamab 
mafodotin ADC and MoA 
Revised program language 
Section 4.2.4  
Updated clinical experience language for 
studies BMA117159 and 205678 
Updated relevant clinical data 
available. 
Section 4.3 
Updated benefit/risk assessment 
Incorporation of revised program 
safety language 
Synopsis, Section 
7.1, Table 17 
Left ventricular ejection Fraction (LVEF) 
by ECHO value for adequate organ 
system function changed from 45% to 
40% 
Based on clinical experience to date 
with belantamab mafodotin, and as 
reviewed by the GSK cardiac safety 
panel, it was agreed that a reduction 
in LVEF was acceptable for 
participants enrolling in the study. 
Synopsis, Section 
7.2, Section 9.2.3 
Removed exclusionary ECG QTcF 
parameter 
Aligned with Cardiac Safety Panel 
recommendations (Dec 2019) 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Synopsis, Section 
7.3 
Lifestyle Restrictions 
• 
Clarified language regarding use of 
bandage contact lenses and when 
contact lenses may be restarted 
following end of study treatment 
• 
Moved the sentence about 
administration of live/live-
attenuated vaccine to prohibited 
concomitant medication.  
Program clarifications and revisions 
 
 
 
 
The text was moved to a more 
appropriate section 
Section 8.2.1,  
Table 22 
Removed the requirement for 
prophylactic corticosteroid eyedrops 
Based on ocular substudy safety data 
from Study 205678 data  
Section 8.2.1,  
Table 23 
Inclusion of dose modification guidelines 
for cutaneous reactions and 
hypersensitivity associated with 
lenalidomide. 
Aligned with updated approved 
lenalidomide labelling. 
Section 8.7.2 
Added administration of live/live-
attenuated vaccine text. See the change 
for Section 7.3 above. 
 
Added restriction on use of 
live/attenuated virus vaccines for at least 
70 days after the last dose of 
belantamab mafodotin 
To enhance patients’ safety, the 
period for prohibited use of live/live-
attenuated vaccines has been 
extended 
 
 
Section 9.2.6 
Addition of reaction management 
language for belantamab mafodotin 
infusion reactions 
Clarification 
Section 10.3 
Updates to belantamab mafodotin, 
lenalidomide and bortezomib overdose 
language; addition of dexamethasone 
overdose section 
Clarification of overdose information 
Section 10.6.7 
Updated specifications for ophthalmic 
examinations 
Revised safety language and 
adjustments for added cohorts 
Study Design Changes 
Section 3, Section 
10.2.1, Section 
12.4.2.2 and Section 
14.9 
Adverse event assessment period 
increased from 45 days to at least 70 
days after the last dose 
Aligned with recent updated 
information regarding belantamab 
mafodotin half-life 
Synopsis, Section 
7.1 
Removal of IMWG reference pertaining 
to disease progression in Inclusion 
Criteria #6 
Due to varied global standards, 
wording in the listed criterion has 
been adjusted to introduce flexibility 
based on global differences 
Section 3, Table 5 
and Table 6 
Serum pregnancy test collection window 
expanded to 10-14 days 
To provide greater flexibility to sites 
in determining pregnancy status 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 3, Table 5 – 
Table 8 
Criteria for collection of BM aspirate for 
 and 
 updated to achieving 
VGPR or better 
Criteria for collection of BM aspirate 
for 
 and 
 updated to 
provide a more detailed disease 
response profile  
 
Synopsis, Table 1, 
Table 5, Figure 1, 
Section 6.1, Section 
6.2, Section 6.5.2, 
Table 18, Section 
8.1.1, Section 8.2.1, 
Section 12.2.1 
Addition of a potential new treatment 
cohort with introduction of Q8W 
(STRETCH) schedule for Arm A 
(belantamab mafodotin with Len/Dex) 
Evaluate other dosing regimens for 
optimal treatment  
Synopsis, Table 2, 
Table 9, Figure 2, 
Section 6.1, Section 
6.2, Section 6.5.2, 
Table 18, Section 
8.1.2.1, Section 
8.1.3, Section 8.2.1, 
Section 12.1.2, 
Section 12.2.2 
Addition of new treatment cohorts and 
introduction of Q6W (STRETCH) and 2.5 
→ 1.9 mg/kg Step-Down (S/D) 
schedules for Arm B (belantamab 
mafodotin with Bor/Dex) 
Evaluate other dosing regimens for 
optimal treatment 
Section 6.1.1, 
Section 6.1.2, 
Section 6.5.1, Table 
13, Section 8.1.1.1 
SINGLE and SPLIT doses at 3.4 mg/kg 
removed from Arm A; Decreased 
number of dose levels for exploration 
and defined maximum dose as 2.5 
mg/kg for belantamab mafodotin 
3.4 mg/kg dose is not currently being 
explored 
Synopsis, Section 
6.2, Section 6.3, 
Section 12.2 
Revised numbers of participants 
Adjusted numbers to accommodate 
new dosing regimen cohorts and 
addition replacements for non-DLT 
evaluable participants 
Section 6.5 
Provide justification for lower dosing and 
different regimens for belantamab 
mafodotin treatment 
Revised due to updated analysis of 
safety information 
Synopsis, Section 
7.1, Section 10.2.8 
WOCBP and male participants in Arm B: 
change the restriction of contraceptive 
period after bortezomib 
Added due to the changes in the 
bortezomib label 
Section 7.3 
The prohibition for blood donation in Arm 
A was changed from 120 days to 28 
days 
Alignment with lenalidomide label 
Section 8.2.1, Table 
20, Table 21 
Removed requirement that dose 
modifications be “after Cycle 1” from Part 
2. 
To provide greater flexibility to sites 
in managing hematological toxicity 
CCI
CCI
CCI
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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 8.2.1, 
Section 8.6, 
Appendix 13, SoA 
Table 4 – Table 10 
Added telemedicine and collection of 
data/follow-up by telephone 
Covid-19-related changes 
Section 10.9 
Revised text for immunogenicity 
assessments 
Update and clarification 
Section 12.4.3.1 
Pharmacokinetic analysis methods 
updated from population PK approach to 
standard noncompartmental analysis, 
data permitting. 
Pharmacokinetic analysis methods 
and population PK approach updated 
to align with program level guidance 
Section 12.4.4 
Updated text on PK/PD assessments 
Revised to match plans for analysis 
Section 12.4.8.1.2 
and 
Section 12.4.8.2.2 
Interim analysis wording modified 
Added additional details around 
planned interim analysis  
Section 12.4.9 
Final Analysis section added  
Clarification 
Section 12.4.5.3 
Revised text on biomarkers analyses 
Update and clarfication 
Section 14.9 
Actions and follow-up assessments 
modified in liver stopping events table 
Clarification 
Section 14.9.1.2 
Addition of statement regarding liver 
stopping event due to hepatitis 
Clarification of protocol in the event 
of alcohol-related hepatitis 
Administrative Changes 
Title Page 
Sponsor signatory changed 
 
Synopsis 
Corrected dose reduction guideline for 
dexamethasone from 75 years of age 
to >75 years of age 
Typographical error 
Table 1 and Table 2; 
Figure 5, Figure 6, 
Figure 7; Table 18 
Tables and figures to specify dosing 
regimens 
Added to clarify cohort differences 
and schedules 
Synopsis; Section 2, 
Section 6.1.2.3, 
Section 8.1.1.1, 
Clarified dose descriptions administered 
on Day 1 of SINGLE dose and on Day 1 
and Day 8 of SPLIT dose regimens. 
Clarification 
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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 8.1.2.1 and 
Table 18 
Synopsis; Section 3, 
Section 7.3, Section 
8.2.1, Section 9.2.5, 
Section 10.6.7 
Replaced reference to ophthalmologist 
and optometrist with “qualified eye care 
specialist” 
To clarify the definition of an eye care 
professional 
Section 6.5 
Description of new dosing schedules in 
Arm B 
Rationale added for explanation and 
justification 
Synopsis; Section 
7.1 
Clarification of inclusion criteria 
contraception language pertaining to 
WOCBP in Arm A vs Arm B. 
Clarification 
Section 3, Table 4 
Clarification to Pregnancy Test for 
WOCBP footnote regarding differences 
between Arm A and Arm B 
Clarification 
Section 3, Table 5-
Table 8; 
Section 10.6.1 
Clarification to Physical Assessment 
footnote that dose should be re-
calculated for body weight change 
>10%. 
Clarification 
Section 3, Table 4-
Table 9 
 testing 
footnote: clarification of 
 
 testing requirements. 
Clarification 
Section 3, Table 4 – 
Table 8 
BM aspirate footnote: clarified BM 
aspirate sampling 
Clarification 
Section 3, Table 5 – 
Table 8 
Footnotes added to study assessments 
for BM aspirate, 
 and PK blood 
sampling for belantamab mafodotin 
Clarification 
Section 3, Table 5 – 
Table 8 
Corneal Events Management: Added “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” to footnote. 
To align with existing language in 
Appendix 8 
Section 3, Table 5 
and Table 6 
Updated Footnote #9: Day 21 corrected 
to Day 22 
To align with standard of care (SoC; 
dexamethasone) dosing schedule 
Section 3, Table 5 
and Table 6  
Pharmacokinetic sampling for 
belantamab mafodotin Dose 2: wording 
change for delay of Dose 2  
Clarification 
CCI
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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 3, Table 7 
and Table 8 
Administration of dexamethasone: 
footnote updated to remove “weekly” 
from “reduced to 10 mg weekly” 
To align with SoC dosing schedule.  
Section 3, Table 8 
Hematology and clinical chemistry 
footnote: removed “to be performed 
every 3 weeks 3 days” and corrected 
“72 h prior” to “24 h prior” 
EORTC QLQ-30 and QLQ-MY20 
collected in Part 2 only changed to Part 1 
and Part 2 
Corrections 
Section 3, Table 10 
Addition of BM sampling considerations 
to BM aspirate/biopsy for Disease 
Assessment  
 
Section 4.3.1, Table 
11 
Updated Data summary/risk rationale 
and mitigation strategy items throughout 
table  
Added Embryo-fetal toxicity section to 
overlapping toxicities section 
Updating to include recent 
information 
Section 4.3.2 
Added discussion of benefits from study 
205678 to benefit assessment 
Updating to include recent 
information 
Section 4.3.3 
Updated benefit/risk conclusions to 
include preliminary safety data from Arm 
B 
Updating to include recent 
information 
Section 6.3 
Language regarding study completion, 
study analyses and end of study updated 
Clarification 
Section 8.1.1.2 
Language throughout section 
streamlined for clarity 
Clarification 
Section 8.1.1.2 and 
Section 8.1.2.2, 
Section 8.1.4.4 
For dexamethasone, added text referring 
to the product label and removed 
DECADRON reference.  
Clarification 
Section 8.1.3.2 and 
Section 8.1.4.3 
Removed references to REVLIMID and 
VELCADE-specific product information, 
replaced with referral to local prescribing 
information  
Broadened references for regional 
variance 
Section 8.2.1, 
Table 21 
Added missing footnote 
Correction/clarification 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 8.2.1, Table 
22 
Added directions for use of cooling eye 
masks to reflect information in SOA 
Clarification to align with SOA 
Section 8.2.1, 
Table 23 
Removed instruction to not dose below 
5 mg daily for Days 1 to 21 of 28-day 
cycle.  
Correction/clarification 
Section 10.6.8, 
Secction 10.11 
Updated text for PRO measures and HR-
QoL assessments 
Revised instructions and conduct 
Section 10.7.1 
Arm A, receiving belantamab mafodotin: 
Q3W corrected to Q4W 
Correction to align with Arm A cycle 
length 
Section 13 
Reference list updated as necessary 
Correction 
Section 14.8, Table 
34 
Corrections to values for changes in 
visual acuity 
Correction/clarification 
Section 14.12 
Appendix added to define eye care 
specialist qualifications and requirements 
Definition of eye care specialist 
required due to language changes 
throughout document. 
Section 14.13 
Added appendix on telemedicine 
procedures 
Added to facilitate adequate care and 
data collection 
Editorial/Document Formatting Changes 
Whole document 
Minor editorial and document formatting 
revisions 
Minor, therefore have not been 
summarized 
Whole document  
GSK2857916, GSK’916 replaced with 
belantamab mafodotin 
Use generic name 
Whole document 
Abbreviate the Step-Down regimen as 
S/D; Abbreviate Q6W regimen as 
‘STRETCH’ 
Ease of reference for dose regimen 
concepts 
 
14.14.2. 
Protocol Amendment 2 (26-APR-2019) from the Final Version (28-
FEB-2018)  
Amendment 2 26-APR-2019 
Where this Protocol Amendment Applies 
Protocol Amendment 2 applies to all countries and sites.  
Overall Rationale for the Amendment: 
i) 
In December 2018, GSK paused enrolment in the belantamab mafodotin in 
combination with lenalidomide/dexamethasone (Arm A) of study 207497 due to two 
similar events of pneumonia and sepsis in the setting of febrile neutropenia resulting in 


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death in the first two patients enrolled in Arm A. The pause in enrolment in Arm A 
occurred per protocol, to assess the dose exploration in this treatment arm. GSK used this 
as an opportunity to review the data and conduct an evaluation to assess factors that led to 
these neutropenic/infection events while amending the protocol. Protocol for study 
207497 is being amended to: a) to change ECOG eligibility criteria in Arm A from 0-2 to 
0-1, b) to include additional guidance for management of neutropenia / prophylaxis of 
infections to be implemented across the study on resuming Arm A and c) more stringent 
hematological monitoring for both Arm A and Arm B. 
ii) 
Regulatory feedback encouraged generation of additional data (safety, PK, PD, 
clinical activity) at lower dose levels of belantamab mafodotin to support dose selection 
for future Phase 3 studies with belantamab mafodotin in combination with standard of 
care (SoC) agents. Administration of belantamab mafodotin divided as two equal 
administrations a week apart will also be evaluated to see if this dosing schedule would 
result in improvement of benefit/risk due to ~25% reduction in the maximum 
concentration while maintaining similar exposure over a cycle compared to the full 
administration on Day 1. 
iii) 
Protocol Amendment 2 also incorporates the Protocol Clarification letter (dated 
28-Feb-2019) previously issued to study sites, that provided updated guidance on grading 
corneal events and dosing participants with belantamab mafodotin.  
iv) 
Administrative corrections and general program updates are also included in 
Amendment 2. 
 
Protocol Amendment 2 includes the following: 
Section # and 
Name 
Description of Change 
Brief Rationale 
Revised Study Design for 207497 
Section 2 
Schedule of  
Activities Tables 
Added SoA Tables 3 and 5 pertaining 
to the belantamab mafodotin SPLIT 
dosing cohorts based on the 
amendment 02-edited existing SoA 
tables (renumbered as Table 2 and 
Table 4, respectively). Additional PK 
timepoints were included for SPLIT 
dosing. 
To align with revised study design 
regarding SPLIT dosing 
Section 4 
Objectives and 
Endpoints 
Table 8: Combined previous Table 6 
and Table 7 into a single table 
To align with revised study design 
Section 5.1 Overall 
Design 
Revised study design 
Based on emerging data 
Section 5.1.1 
Arm A 
Figure 2: Replaced Figure with Study 
Design for Arm A 
Updated section to specifically refer 
To clarify and to align with revised 
study design 


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Section # and 
Name 
Description of Change 
Brief Rationale 
to Arm A  
 
Figure 3: Updated dose-finding 
criteria pertaining to Arm A and 
changed number of figure from 4 to 3 
To align with revised study design 
and number of participants in the 
protocol 
 
Table 10: Added table for operating 
characteristics of the dose escalation 
rules for Arm A 
To align with revised study design 
Section 5.1.2 
Arm B 
Added section specific to Arm B  
 
Figure 4: Replaced Figure with Study 
Design for Arm B and updated figure 
number from 3 to 4 
 
To clarify and to align with revised 
study design 
Section 5.2 
Number of 
Participants 
Updated number of participants 
To align with revised study design 
Section 5.4 
Scientific Rationale 
for Study Design 
Edited rationale and removed 
reference to recommended phase 2 
dose (RP2D) 
To clarify the scientific rationale 
and to align with revised study 
design and strategy across the 
belantamab mafodotin 
development program 
Section 5.5.1 
Starting dose of 
belantamab 
mafodotin 
Added language for divided 
administration of belantamab 
mafodotin (SPLIT dosing) 
To align with revised study design 
Section 7.1 
Treatments 
Administered  
Sections 7.1.1.1,Section 7.1.2.1 – 
Added guidance for SPLIT dosing 
schedule for belantamab mafodotin 
and language for potential 
exploration of alternate dosing 
schedule 
To provide consistency and 
alignment with revised study 
design 
Section 9.6.1 
Physical 
Examinations 
Included timeframe for the SPLIT 
dosing cohorts 
To align with revised study design 
and new SoA Table 3 and Table 5 
in Section 2 
Section 11 
Statistical 
Considerations 
Edited section to include distinct 
sections for Arm A and Arm B 
To align with revised study design 
Section 11.1.1.2 
(Arm A) and 
Edited statistical hypotheses for Part 
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Section # and 
Name 
Description of Change 
Brief Rationale 
11.1.2.2 (Arm B) 
Part 2 
2 
Section 11.2.1.2 
(Arm A) and 
11.2.2.2 (Arm B) 
Sample size 
determination Part 
2 
Added language on sample size 
estimation  
To clarify calculation of sample 
size 
Section 11.3 
Population for 
analysis 
Removed definition of “all evaluable 
population” 
To align with revised study design 
Section 11.4.1 
Analyses of clinical 
activity 
Updated primary and secondary 
endpoints 
To be consistent with changes in 
Section 4 - Objectives/Endpoints 
Section 11.4.7 
Section 11.4.7.1.1 
(Arm A) and 
Section 11.4.7.2.1 
(Arm B) Interim 
Analysis Part 1 
Added language on analyses 
performed during dose escalation 
To clarify based on the revised 
study design 
Section 13 
Appendices 
Appendix 11– Appendix added to the 
protocol 
To align with protocol updates 
Study Specific Safety Changes 
Section 2 
Schedule of  
Activities Tables 
Table 2 & Table 4: Added 
requirement for ANC prior to dosing 
Changes made following safety 
events and to enhance safety 
monitoring 
 
 
Table 2: Clarified lenalidomide 
administration timing in relation to 
belantamab mafodotin administration 
timing 
Information added to provide 
clarity and keep consistency with 
PK sample collection and add a 
safety window between 
administration of belantamab 
mafodotin and lenalidomide.  
 
 
Table 2 & Table 4: Added an 
additional hematology sample 
collection on Day 15 for Cycles 1-8 
Changes made to add additional 
safety monitoring 
 
Section 3.3.1 Risk 
Assessment 
Table 7: Updated table to highlight 
overlapping toxicities for belantamab 
mafodotin with SoC 
To clarify risks associated with 
administration of belantamab 
mafodotin with Len/Dex and 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Bor/Dex 
Table 7: Added language for 
methods of contraception in Arm A 
and B 
Added clarification for method of 
contraception in accordance to the 
safety profile of each drug 
including requirements from 
REVLIMID REMS program. 
 
Table 7: Updated information on 
thrombocytopenia and neutropenia 
risks related to belantamab mafodotin 
and revised mitigation strategy 
Updated based on data from the 
FTIH study BMA117159 
Section 6.1 
Inclusion Criteria 
For Arm A, changed ECOG 
performance status from 2 to 1 
The changes were made following 
safety events and to enhance 
safety monitoring 
 
 
Table 13: Increased limit for Absolute 
Neutrophil Count and Platelets  
 
 
Table 13: Removed Coagulation 
section and updated footnote 
Added language for contraception 
methods and female partner of male 
participants 
Added inclusion criteria for WOCBP 
participants assigned to treatment A 
 
Section 7.1 
Treatments 
Administered 
Added recommendation for time of 
administration of lenalidomide 
To clarify and to keep consistency 
with PK sample collection and add 
a safety window between 
administration of belantamab 
mafodotin and lenalidomide 
 
Added guidance for dose 
modification of dexamethasone 
To provide guidance and align 
with addition of Section 7.2.2 
Section 7.1.5.3 
Lack of tolerability 
in Treatment A or 
B  
Added language for participant who 
meets stopping criteria for 
belantamab mafodotin 
To clarify follow up for participant 
who meets stopping criteria 
Section 7.2.1 Dose 
Modification After 
Cycle 1 
Table 16:  
• Added monitoring for 
Neutropenia 
Updated based on emerging data 


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Section # and 
Name 
Description of Change 
Brief Rationale 
 
• Edited dose modification 
guidelines for thrombocytopenia 
to reflect the SINGLE day and 
SPLIT dosing schedules 
 
 
• Added immediate hospitalization 
for participants presenting with 
febrile neutropenia 
 
 
• Corneal events monitoring 
removed and presented in a 
separate table (Table 17) 
 
 
• Added language clarifying 
infusion reaction symptoms 
To clarify recommendations for 
infusion reactions 
 
Table 19: Added monitoring for 
hematological toxicity 
Updated information based on 
emerging data 
Section 7.2.2 Dose 
Modification 
Guidelines for 
Dexamethasone 
Added section, Table 20 and Table 
21 
To provide guidance for dose 
modifications for dexamethasone 
Section 7.7.2 
Prohibited 
Medication 
Added caution statement for CYP 
inhibitors/inducers 
Updated information based on 
emerging data  
Section 8.1 
Discontinuation of 
Study Treatment 
Added Pregnancy and Safety 
stopping criteria to the list of reasons 
for discontinuation 
To align with Section 9.2.8 and 
Appendix 7  
Section 8.2.5 
Corneal 
Supportive Care 
Guidelines 
Removed section – content moved to 
Section 9.6.7 Ophthalmic 
Examinations 
To provide cohesion and group 
related content 
Section 11.4.7.1.2 
(Arm A) and 
11.4.7.2.2 (Arm B) 
Interim Analysis 
Part 2 
Added language on safety monitoring 
and stopping rules during cohort 
expansion 
To align with strategy across the 
belantamab mafodotin 
development program 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Belantamab Mafodotin Program Level Changes 
Section 2 
Schedule of  
Activities Tables 
Table 2 & Table 4: Edited 
hematologic examination timeframes 
to include additional testing during 
each cycle 
To align with strategy across the 
belantamab mafodotin 
development program 
 
Table 2, Table 4, Table 6: Changed 
duration of collection of AE/SAE from 
30 days to 45 days 
Changed throughout the protocol 
Revised to align with duration of 
5 half-lives of belantamab 
mafodotin 
 
Table 2 & Table 4: Revised Corneal 
Event prophylaxis to also include 
prednisolone acetate 
To align with strategy across the 
belantamab mafodotin 
development program 
Section 3.3.1 Risk 
Assessment 
Table 7: Updated data and mitigation 
strategy on risks related to 
belantamab mafodotin 
(thrombocytopenic events, 
neutropenic events, IRR, 
cardiotoxicity, nephrotoxicity, 
pulmonary toxicity, 
immunosuppression, potential for 
other laboratory abnormalities) 
Edited based on updated data 
from the FTIH study (BMA117159) 
and to align with strategy across 
the belantamab mafodotin 
development program 
Section 6.2 
Exclusion Criteria 
Changed the definition of invasive 
malignancies to be excluded 
 
Increased QTcF from 470 msec to 
480 msec  
To clarify the definitions 
 
 
QTcF increased to align with GSK 
internal standards for oncology 
trials as determined by GSK 
Cardiac Safety Panel 
 
 
Changed uncontrolled arrhythmias to 
untreated arrhythmias 
 
Reduced timeframe for history of 
myocardial infarction, acute coronary 
syndromes prior to Screening 
 
Based on emerging data as 
determined by GSK Cardiac 
Safety Panel 
 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 7.1 
Treatments 
Administered 
Sections 7.1.1.1, 7.1.2.1 and Table 
11 – Changed duration of 
administration of belantamab 
mafodotin from “30 min” to “30 min to 
1 h” 
To add flexibility in the duration of 
administration of belantamab 
mafodotin 
 
Removed language indicating that 
participants will be removed from 
study for lack of tolerability  
To align with strategy across the 
belantamab mafodotin 
development program 
Section 7.1.12.4 
Participants 
Achieving CR 
Removed section 
Section not relevant for 
GSK2857916 
Section 7.2.1 Dose 
Modification After 
Cycle 1 
Table 15: Added table for 
recommendations for dose reduction 
of belantamab mafodotin 
To clarify and align with revised 
study design 
 
Table 18: Added recommendation for 
use of prophylactic antimicrobials 
Changes to dose modification 
guidelines for belantamab 
mafodotin related to Corneal 
Events further clarified dose 
modifications based on visual 
acuity or findings on ophthalmic 
examination 
Section 8.2.5 
Corneal Event 
Stopping Criteria 
Added clarity on use of GSK scale 
and CTCAE scale for AESI reporting 
purposes and dose modifications 
Removed duplicate text within 
section 8.2.5 
Alignment throughout protocol. 
Both the CTCAE and GSK scale 
are to be utilized for reporting of 
corneal events and clarified that 
the GSK scale is to be utilized for 
dose modification decisions. 
Section 9.2.7 
Adverse Events of 
Special Interest 
Added clarity on use of GSK scale 
and CTCAE scale 
Alignment throughout protocol 
Section 9.2.8 
Pregnancy 
Edited timeframe for performance of 
pregnancy test prior to the first dose 
of study treatment from 72 h to 24 h 
To keep protocol consistency for 
pregnancy monitoring across the 
belantamab mafodotin 
development program 
Section 9.6.10 
Laboratory 
Assessments 
Table 22: Removed INR analysis 
To align with GSK liver monitoring 
requirements, INR test will not be 
required unless a liver event 
occurs 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 13 
Appendices 
Removed Appendix 3 – International 
Myeloma Working Group (IMWG) 
Criteria for Relapse-Refractory 
Multiple Myeloma 
Included references to the IMWG 
Criteria in lieu of an appendix for 
clarification purposes 
 
Appendix 10 – Labelling changed to 
Appendix 8 - Added clarity on use of 
GSK scale and CTCAE scale – 
Updated GSK grading scale 
To align with Section 9.2 and 
throughout the protocol 
 
 
Appendix 9 – PK collection updated 
from 30 days to 45 days (5 half-lives) 
Revised to align with duration of 5 
half-lives of belantamab mafodotin 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Additional Changes in Assessments 
Section 2 
Schedule of  
Activities Tables 
Table 1: Edited FISH testing to 
include identification of amplifications 
and deletions 
Acceptability of positive results for 
high risk abnormalities by FISH 
has been extended beyond 60 
days, as the listed abnormalities 
are myeloma-defining and do not 
change the course of the disease 
 
Table 2 & Table 4: Clarified timings 
for vital signs, ECG collections and 
PK sample collection 
 
Additional ECG timepoints added 
to assess at the Cmax of the free 
cytotoxic drug (cys-mcMMAF) and 
to detect any delayed effects on 
QTc 
 
 
Table 2 & Table 4: Added additional 
PK timepoints 
 
Additional PK timepoints added to 
capture the Cmax of the free 
cytotoxic drug (cys-mcMMAF) and 
to better define the kinetics of cys-
mcMMAF and the elimination 
phase of ADC and cys-mcMMAF 
 
 
Table 2 & Table 4: Added additional 
 sample collection timepoint  
To study the effect of genetic 
variations on response 
Protocol Clarification and Alignment Changes 
Section 2 
Schedule of  
Activities Tables 
Table 2: Changed timeframe from 
pregnancy testing in WOCBP 
To provide consistency and 
alignment throughout the protocol 
 
Section 5.3 
Participant and 
Study Completion 
Edited definition of participant 
completion 
To clarify study completion  
 
Edited definition for end of study for 
Arms A and B 
To clarify definition for end of 
study 
Section 5.5.2 
Starting dose of 
Added “planned” to “cycle” 
To clarify between time bound 
assessments and cycle bound 
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Section # and 
Name 
Description of Change 
Brief Rationale 
SOC 
assessments  
Section 6.1 
Inclusion Criteria 
Added “autologous” to “stem cell 
transplant” 
To clarify inclusion criteria 
 
Section 7.2.1 Dose 
Adjustments Due 
to Body Weight or 
Body Surface Area 
Moved content to relevant context in 
Section 7.1 
To clarify protocol 
Section 7.2.2. 
belantamab 
mafodotin Dose 
Modification in Part 
1 (Dose 
Escalation) 
Moved content to Section 5.1 
To clarify protocol 
Section 5.1.3 
Criteria for 
belantamab 
mafodotin Dose-
Limiting Toxicity in 
Part 1 
Moved this Section (previously 
Section 7.2.3) into Section 5.1  
To clarify protocol 
Section 7.2.1 
Dose Modification 
After Cycle 1 
Removed presented scenarios – to 
be provided as an Appendix to the 
SRM 
To clarify protocol 
Section 9.6.3 Vital 
Signs 
Added language for timeframe of vital 
signs assessment on days of 
bortezomib administration 
To provide consistency and 
alignment throughout the protocol 
Section 9.6.7 
Ophthalmic 
Examinations 
Added clarification for supportive 
care. 
 
To provide consistency and 
alignment throughout the protocol 
Administrative Changes 
Title Page 
Removed author list 
 
Removed Medical Monitor 
information and added reference to 
the Study Reference Manual 
To follow current GSK template 
(i.e., Transcelerate protocol 
template) 
Section 1 Synopsis Changed text in Synopsis to reflect 
changes to the text of main body of 
Refer to individual items listed 
throughout this table 


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Section # and 
Name 
Description of Change 
Brief Rationale 
the protocol 
Section 9.6.7 
Ophthalmic 
Examinations 
Clarification of examination 
requirement for each visit. 
 
Added statement on the central 
collection of photographs 
Administrative change 
Section 9.6.10 
Laboratory 
assessments 
Table 22: Removed “fasting” 
requirement for glucose analysis 
Based on additional data, fasting 
glucose is not required at every 
visit as routine glucose is included 
in chemistry panel 
Section 13 
Appendices 
Removed Appendix 7 – Calculation 
of Body Surface Area 
Removed to prevent copyright 
infringement 
 
Appendix 12 – Included list of 
changes pertaining to Amendment 01 
To follow current GSK template 
(i.e., Transcelerate protocol 
template) 
Editorial/Document Formatting Changes 
Whole document 
Minor editorial and document 
formatting revisions 
Minor, therefore have not been 
summarized 
14.14.3. 
Protocol Amendment 1 (7-MAY-2018): 
Protocol Amendment 1 include following: 
• 
additional authors who contributed to protocol amendment were added 
• 
change in the Primary Medical Monitor 
• 
Changes made in the Schedule of Activities tables. The SOA tables have been 
modified to reflect that the disease assessments need to be performed at regular 
intervals instead of being linked to the administration of study drugs. Revisions have 
also been made in the timings and frequency of some assessments. 
• 
Minor correction made in the participants’ eligibility criteria; participants with prior 
allogenic SCT will now be excluded (Section 6). 
• 
Clarification made on dose delays of study drugs by giving examples of different 
scenarios (Section 7.2). 
• 
All routine and disease evaluation related blood and urine tests now will be done 
locally; centrally only if unable to perform locally (Table 16) 
• 
Administrative changes made throughout the document. 
 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Title Page 
Authors list was updated. 
Additional authors who 
contributed to protocol 
amendment were added to the 
list; authors who are no longer 
involved with the study were 
removed. 
Medical 
monitor/Sponsor 
Information Page 
GSK Medical Monitor change 
Change in the Primary Medical 
Monitor 
Section 2 
Schedule of 
Activities Tables 
Significant changes made in the 
Schedule of Activities tables.  
• The SOA Table 2 & Table 3 have 
been modified to reflect that the 
disease assessments need to be 
performed at regular intervals 
instead of being linked to the 
administration of study drugs. For 
this purpose, an additional column 
for fixed time interval assessments 
was added. 
• Time period windows have been 
added for vital signs, drug infusions, 
PK sampling and imaging.  
• Revisions have also been made in 
the timings and frequency of 
following assessments; Spot urine 
for albumin/creatinine ratio, ECHO, 
imaging and EORTC QLQ-C30 AND 
QLQ-MY20 questionnaires. 
• Timepoints for response 
assessments under disease 
evaluation modified. 
• Removal of flow cytometry for bone 
marrow aspirate. 
• Added whole body PET/CT to 
confirm CR, sCR. 
• Timings of Triplicate ECG at the End 
of Infusion (EOI) corrected. 
 
• Language on the genetic research 
 
 
• Cycle bound assessments 
have been separated from 
time bound assessments to 
clarify activities. 
 
 
 
 
• This change was made to 
avoid deviations from 
administration timings of 
these assessments. 
• To align the assessments in 
both treatment arms. 
 
 
 
 
• Per IMWG response criteria 
 
 
• Flow cytometry is not used in 
IMWG (Rajkumar 2016) 
• Based on IMWG (Rajkumar 
2016) 
• ECG recordings must be 
made prior to EOI instead of 
post-infusion as stated in the 
original version of the 
protocol. 
 


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Section # and 
Name 
Description of Change 
Brief Rationale 
sample collection modified. 
• To add more clarity. 
 
Synopsis and 
Section 4 
Secondary 
Objectives  
Definition of 
 
 modified. 
The change was made to 
provide precise definition of 
 
Section 6 
Study Population 
Minor correction made in the 
participants’ eligibility criteria; 
participants with prior allogenic SCT will 
now be excluded.  
To reflect the above, inclusion criterion 
#9 deleted and exclusion criterion # 4 
added in synopsis and main body of the 
protocol.  
Participants with Allogenic SCT 
are now excluded to avoid 
unpredictable toxicity.  
 
Section 7.2.4 
Dose 
Modification After 
Cycle 1 
Clarification provided regarding dose 
delays of study drugs by giving 
examples of different scenarios. 
The change was made to 
provide guidance on dose 
interruptions and reductions. 
Section 8.2.7 
Infusion Related 
Reaction 
Management and 
Stopping Criteria 
Clarification provided on management of 
infusion-related reactions and stopping 
criteria. 
The change was made to add 
more clarity. 
Section 9.2 
Adverse Events 
Guidance provided on the grading of 
adverse events. 
 
Added language specifying 
grading for clarity 
Section 9.2.6 
Disease-Related 
Events and/or 
Disease Related 
Sentence on the reporting of 
progression disease as a serious 
adverse event modified. 
Updated text to ensure PD is 
not reported as a SAE 
Section 9.6.7.1 
Ocular 
Examination and 
Added slit lamp in full anterior segment 
examination for clarity 
The change was made to add 
more clarity. 
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Section # and 
Name 
Description of Change 
Brief Rationale 
Procedures 
Section 9.7.1 
Blood Sample 
Collection for 
Pharmacokinetics 
Amount of blood volume needed for 
belantamab mafodotin, Lenalidomide 
and Bortezomib Pharmacokinetics 
samples removed. 
Information on the PK blood 
volume will be contained in the 
SRM. 
Table 16 
List of Clinical 
Laboratory Tests 
All routine and disease evaluation 
related blood and urine tests will now be 
done locally; they may be performed 
centrally only if unable to be performed 
locally 
For ease of performing 
assessments and to provide 
more flexibility to sites. 
Appendix 8 
Assessment of 
Intensity 
The intensity assessment scale for 
AE/SAE changed from mild, moderate 
and severe into grades. 
Per new protocol template 
Whole Document 
Administrative corrections were made 
throughout the protocol to correct minor 
inconsistencies and rectify the 
typographical errors 
Provide clarity and correction. 
 


Signature Page for  207497 TMF-14624358 v1.0
Signature Page for TMF-14624358 v1.0
Reason for signing: Approved
Name: 
Role: Approver
Date of signature: 30-Jun-2022 12:13:18 GMT+0000
PPD

SAP_001.pdf: 
Statistical Analysis Plan
Study ID:  207497
Official Title of Study: Reporting and Analysis Plan for A Phase I/II, 
Open-label, Dose Escalation and Expansion Study to Evaluate Safety, Tolerability, 
and Clinical Activity of the Antibody-Drug Conjugate GSK2857916 Administered in 
Combination with Lenalidomide Plus Dexamethasone (Arm A), or Bortezomib Plus 
Dexamethasone (Arm B) in Participants with Relapsed /Refractory Multiple 
Myeloma – (DREAMM 6)
NCT ID : NCT03544281
Date of Document: 25 April 2023


 
CONFIDENTIAL 
The GlaxoSmithKline group of companies 
 
207497 
 
1 
 
Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
 
Title 
: Reporting and Analysis Plan for A Phase I/II, Open-label, Dose 
Escalation and Expansion Study to Evaluate Safety, Tolerability, 
and Clinical Activity of the Antibody-Drug Conjugate 
GSK2857916 Administered in Combination with Lenalidomide 
Plus Dexamethasone (Arm A), or Bortezomib Plus 
Dexamethasone (Arm B) in Participants with Relapsed / 
Refractory Multiple Myeloma – (DREAMM 6) 
Compound Number  : GSK2857916 
Effective Date  
: Refer to Document Date 
 
Description: 
• 
The purpose of this RAP is to describe the planned analyses and outputs to be included 
in the Clinical Study Report for Protocol 207497 (DREAMM 6) [GSK Document No. 
TMF-14624358, Dated: 2022-JUN-30]. 
• 
This RAP is intended to describe the efficacy, safety, pharmacokinetic (PK), 
pharmacodynamic (PD), and patient reported outcome (PRO) analyses required for the 
study.  
• 
This RAP will be provided to the study team members to convey the content of the 
Interim Analysis (IA) and Statistical Analysis Complete (SAC) deliverables. 
 
RAP Author(s): 
Author 
Approval Method 
 
Email 
Statistics Leader (Oncology, Clinical Statistics) 
 
Email 
 (Clinical Pharmacology Modeling & 
Simulations Complimentary Worker, Accuro for 
GSK) 
Copyright 2023 the GSK group of companies. All rights reserved. Unauthorised copying 
or use of this information is prohibited. 
 
 
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RAP Team Approvals  
Reviewers 
Approval Method 
 
Email 
Principal Programmer/Analyst (Oncology, Clinical Programming) 
 
Email 
, Clinical Development  
 
Email 
Clinical Scientist (Oncology, Clinical Development) 
 
Email 
, SMG Pharma Safety (SERM Dev Oncology Scientists) 
 
Email 
 (R&D GCSD) 
 
Email 
, PCO Strategy and Engagement  
(Development – Global Med – VEO – VE Oncology) 
 
Email 
 (Dev-GCO-Rx GCD-Medical 
Writing & Clin Submission) 
 
Email 
 – Precision Medicine and Companion Diagnostics, 
Oncology-EMU-MTT Precision Med & Comp Diagnostics 
Clinical Statistics and Clinical Programming Line Approvals (Method: Veeva Vault 
TMF eSignature): 
Approver 
 
 (Oncology, Clinical Programming) 
 
 (Dev Biostats Stats Onc) 
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TABLE OF CONTENTS 
 
 
PAGE 
1. 
INTRODUCTION ...................................................................................................... 7 
1.1. 
RAP Amendments ........................................................................................ 8 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION ................................................ 11 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan .......................... 11 
2.2. 
Study Objective(s) and Endpoint(s)............................................................. 12 
2.3. 
Study Design .............................................................................................. 15 
2.3.1. 
Overall Design ............................................................................. 15 
2.4. 
Statistical Hypotheses / Statistical Analyses ............................................... 20 
2.4.1. 
Arm A - Belantamab Mafodotin with Len/Dex ............................... 20 
2.4.2. 
Arm B - Belantamab Mafodotin with Bor/Dex ............................... 20 
3. 
PLANNED ANALYSES .......................................................................................... 21 
3.1. 
Interim Analyses ......................................................................................... 21 
3.1.1. 
Arm A – Belantamab Mafodotin with Len/Dex .............................. 21 
3.1.2. 
Arm B- Belantamab Mafodotin with Bor/Dex ................................ 27 
3.2. 
Final Analyses ............................................................................................ 31 
4. 
ANALYSIS POPULATIONS ................................................................................... 32 
4.1. 
Protocol Deviations ..................................................................................... 32 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 33 
5.1. 
Study Treatment & Sub-group Display Descriptors ..................................... 33 
5.2. 
Baseline Definitions .................................................................................... 34 
5.3. 
Examination of Covariates, Other Strata and Subgroups ............................ 35 
5.3.1. 
Examination of Subgroups ........................................................... 35 
5.4. 
Other Considerations for Data Analyses and Data Handling 
Conventions ................................................................................................ 36 
6. 
STUDY POPULATION ANALYSES ....................................................................... 37 
6.1. 
Overview of Planned Study Population Analyses ........................................ 37 
6.2. 
Disposition of Participants ........................................................................... 37 
6.3. 
Demographic and Baseline Characteristics ................................................. 37 
6.4. 
Treatment Compliance ................................................................................ 38 
6.5. 
Extent of Exposure ..................................................................................... 38 
6.6. 
Concomitant Medications ............................................................................ 40 
7. 
EFFICACY ANALYSES .......................................................................................... 42 
7.1. 
Primary Efficacy Analyses .......................................................................... 42 
7.1.1. 
Endpoint/Variables ....................................................................... 42 
7.1.2. 
Summary Measure ...................................................................... 45 
7.1.3. 
Population of Interest ................................................................... 45 
7.1.4. 
Statistical Analyses / Methods ..................................................... 45 
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8. 
SAFETY ANALYSES ............................................................................................. 51 
8.1. 
Adverse Events Analyses ........................................................................... 51 
8.2. 
Adverse Events of Special Interest Analyses .............................................. 53 
8.2.1. 
Belantamab Mafodotin ................................................................. 53 
8.2.2. 
Corneal events (GSK scale)......................................................... 55 
8.2.3. 
Eye Disorder (CTCAE) ................................................................. 56 
8.3. 
Deaths and Serious Adverse Events ........................................................... 56 
8.4. 
Adverse Events Leading to Discontinuation and Dose Modification ............ 57 
8.5. 
Ocular findings from ophthalmic exam ........................................................ 57 
8.6. 
Pregnancies ................................................................................................ 58 
8.7. 
Clinical Laboratory Analyses ....................................................................... 58 
8.8. 
Other Safety Analyses ................................................................................ 59 
8.8.1. 
ECG ............................................................................................. 59 
8.8.2. 
Anti-Drug Antibody Analyses ....................................................... 59 
8.8.3. 
Profile Plot ................................................................................... 59 
9. 
PHARMACOKINETIC ANALYSES ......................................................................... 60 
9.1. 
Drug Concentration Measures .................................................................... 60 
9.2. 
Derived Pharmacokinetic Parameters ......................................................... 60 
9.2.1. 
Belantamab Mafodotin, Total mAb, and Cys-mcMMAF ................ 60 
9.2.2. 
Lenalidomide and Bortezomib ...................................................... 62 
9.3. 
Summary Measure ..................................................................................... 63 
9.4. 
Population of Interest .................................................................................. 63 
9.5. 
Statistical Analyses / Methods .................................................................... 63 
10. PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSES ........................... 64 
10.1. 
Exposure-Response for Efficacy and Safety Endpoints .............................. 64 
11. POPULATION PHARMACOKINETIC (POPPK) ANALYSIS ................................... 64 
13. PATIENT REPORTED OUTCOMES ANALYSES .................................................. 67 
13.1. 
Compliance of PRO-CTCAE, OSDI, and EORTC QLQ-C30 ....................... 67 
13.2. 
Patient Reported Outcome Version of the Common Term Criteria 
for Adverse Events (PRO-CTCAE) ............................................................. 67 
13.3. 
Visual Function Questionnaires .................................................................. 68 
13.3.1. 
National Eye Institute Function Questionnaire-25 (NEI-
VFQ-25) ....................................................................................... 68 
13.3.2. 
Ocular Surface Disease Index ..................................................... 68 
13.4. 
Value Evidence and Outcome ..................................................................... 69 
13.4.1. 
European Organization for Research and Treatment of 
Cancer Quality of Life Questionnaire 30-item Core module 
(EORTC QLQ-C30) ..................................................................... 69 
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13.4.2. 
European Organization for Research and Treatment of 
Cancer Quality of Life Questionnaire 20-item Multiple 
Myeloma module (EORTC QLQ-MY20) ....................................... 70 
14. REFERENCES ....................................................................................................... 71 
15. APPENDICES ........................................................................................................ 73 
15.1. 
Appendix 1: Assessment Windows ............................................................. 73 
15.2. 
Appendix 2: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................ 74 
15.2.1. 
Study Phases .............................................................................. 74 
15.2.2. 
Study Phases for Vital signs, ECG and Laboratory Values .......... 75 
15.2.3. 
Treatment Emergent and On-treatment Flag for Adverse 
Events ......................................................................................... 75 
15.3. 
Appendix 3: Data Display Standards & Handling Conventions .................... 76 
15.3.1. 
Reporting Process ....................................................................... 76 
15.3.2. 
Reporting Standards .................................................................... 77 
15.3.3. 
Reporting Standards for Pharmacokinetic Data ........................... 78 
15.3.4. 
Extended Loss to Follow-up or Extended Time without an 
Adequate Assessment ................................................................. 79 
15.3.5. 
Additional Guidance on Grading Based on Changes in 
Visual Acuity ................................................................................ 80 
15.4. 
Appendix 4: Derived and Transformed Data ............................................... 81 
15.4.1. 
General ........................................................................................ 81 
15.4.2. 
Study Population .......................................................................... 82 
15.4.3. 
Safety .......................................................................................... 83 
15.4.4. 
Biomarker and/or Pharmacodynamic Data ................................... 83 
15.5. 
Appendix 5: Reporting Standards for Missing Data ..................................... 84 
15.5.1. 
Premature Withdrawals ................................................................ 84 
15.5.2. 
Handling of Missing Data ............................................................. 84 
15.6. 
Appendix 6: Values of Potential Clinical Importance ................................... 88 
15.7. 
Appendix 7: Pharmacokinetic / Pharmacodynamic Analyses ...................... 89 
15.7.1. 
Pharmacokinetic / Pharmacodynamic Dataset 
Specification ................................................................................ 89 
15.7.2. 
Pharmacokinetic / Pharmacodynamic Methodology ..................... 89 
15.8. 
Appendix 8: Population Pharmacokinetic (PopPK) Analyses ...................... 90 
15.8.1. 
Systems ....................................................................................... 90 
15.8.2. 
Data Assembly............................................................................. 90 
15.8.3. 
Model Development ..................................................................... 90 
15.8.4. 
Model Qualification ...................................................................... 91 
15.9. 
Appendix 9: Patient Reported Outcomes .................................................... 92 
15.9.1. 
EORTC QLQ-C30 ........................................................................ 92 
15.9.2. 
EORTC QLQ-MY20 ..................................................................... 94 
15.9.3. 
NEI-VFQ-25 ................................................................................. 95 
15.10. Appendix 10: COVID-19 Impact .................................................................. 98 
15.11. Appendix 11: Abbreviations & Trademarks ................................................. 99 
15.11.1. Abbreviations ............................................................................... 99 
15.11.2. Trademarks ............................................................................... 100 
15.12. Appendix 12: List of Data Displays............................................................ 101 
15.12.1. Data Display Numbering ............................................................ 101 
15.12.2. Deliverables ............................................................................... 101 
15.12.3. Study Population Tables ............................................................ 102 


 
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15.12.4. Efficacy Tables .......................................................................... 124 
15.12.5. Efficacy Figures ......................................................................... 129 
15.12.6. Safety Tables ............................................................................. 132 
15.12.7. Safety Figures ........................................................................... 161 
15.12.8. Pharmacokinetic Tables ............................................................. 163 
15.12.9. Pharmacokinetic Figures ........................................................... 167 
15.12.10. Biomarker Tables ....................................................................... 173 
15.12.11. Biomarker Figures ..................................................................... 174 
15.12.12. Patient Reported Outcomes Tables ........................................... 176 
15.12.13. Patient Reported Outcomes Figures .......................................... 185 
15.12.14. ICH Listings ............................................................................... 200 
15.12.15. Non-ICH Listings ........................................................................ 206 
15.13. Appendix 13: Example Mock Shells for Data Displays .............................. 210 


 
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1. 
INTRODUCTION 
The purpose of this reporting and analysis plan (RAP) is to describe the safety, 
tolerability, and efficacy analyses required for interim and final analyses and to describe 
the analyses to be included in the Clinical Study Report for Protocol 207497:  
Protocol Revision Chronology: 
2017N330850_00 
2018-FEB-28 
Original 
2017N330850_01 
2018-MAY-07 
Amendment 01 
The protocol has been amended to include the following: • 
additional authors were added, change in the Primary 
Medical Monitor, changes made in the Schedule of 
Activities tables, minor correction made in the participants’ 
eligibility criteria, clarification made on dose delays of study 
drugs by giving examples of different scenarios, all routine 
and disease evaluation related blood and urine tests now 
will be done locally; centrally only if unable to perform 
locally, and administrative changes made throughout the 
document. 
2017N330850_02 
2018-MAY-14 
Amendment 01 (republished) 
Republishing of protocol amendment 1 2017N330850_01. 
2017N330850_03 
2019-APR-26 
Amendment 02 
The protocol has been amended to change ECOG 
eligibility criteria in Arm A from 0-2 to 0-1, b) to include 
additional guidance for management of neutropenia / 
prophylaxis of infections to be implemented across the 
study on resuming Arm A and c) more stringent 
hematological monitoring for both Arm A and Arm B. Also, 
regulatory feedback encouraged generation of additional 
data (safety, PK, PD, clinical activity) at lower dose levels 
of GSK2857916 to support dose selection for future Phase 
3 studies with GSK2857916 in combination with standard 
of care (SoC) agents. Protocol Amendment 2 also 
incorporates the Protocol Clarification letter (dated 
28-Feb-2019) previously issued to study sites, that 
provided updated guidance on grading corneal events and 
dosing participants with GSK2857916. Administrative 
corrections and general program updates are also included 
in Amendment 2. 
2017N330850_04 
2020-JUL-13 
Amendment 03 
The protocol has been amended to include updated 
duration of contraception for female participants to align 
with this guidance of childbearing potential based on 
review of guidelines on aneugens. Additionally, upon 
review of safety data from Study 205678 (DREAMM-2), it 
was determined that ocular changes associated with 
belantamab mafodotin treatment were mostly limited to the 
corneal epithelium [GSK Document Number 2013N175128 
V08, 2020]. Therefore, further collection of ocular safety 


 
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data in belantamab mafodotin studies will be focused on 
corneal changes. Preclinical data from xenograft mouse 
models and emerging clinical data from Arm A in 
Amendment 2 suggests greater activity of belantamab 
mafodotin in combination with lenalidomide. Given this, 
doses higher than 2.5 mg/kg of belantamab mafodotin will 
not be evaluated in combination with lenalidomide/ 
dexamethasone in Arm A in Amendment 3. Furthermore, in 
order to reduce increased exposure of belantamab 
mafodotin over time and potentially improve the benefit/risk 
for participants, reduced dose levels and extended dosing 
schedules for belantamab mafodotin will be evaluated in 
Amendment 3. 
TMF-14624358 
2022-JUN-30 
Amendment 04 
The protocol has been amended to allow continued 
treatment of study participants who continue to derive 
clinical benefit post the final analysis, update for changes 
made per the latest IB, match plans for final statistical 
analysis, and support deliverables for final CSR and to 
implement PACT. 
 
All data displays (Tables, Figures & Listings) will use the term “Subject” which reflects 
CDISC and GSK Data Display Standards terminology” 
1.1. 
RAP Amendments 
Revision chronology:  
RAP Section 
Amendment Details 
Reporting and Analysis Plan_Study207497_Final_V1 [18-NOV-2020] 
Statistical Analysis Plan RAP Amendment 1 [30-AUG-2021] 
Various sections 
• 
Updated use of the word “participants” instead of “subjects,” except 
within Appendix 12 and sections referring to the list of data displays.  
Section 2.1 
• 
Added 
” as an additional method of assessment of 
clinical activity. 
Section 3.1. Interim 
Analyses 
• 
Edited paragraph and page break formatting. 
Section 5.1 Study 
Treatment & Sub-group 
Display Descriptors 
• 
Updated “Data Display” labelling, as per interim 1 review, adding 
combination name. 
Section 6.3 Demographic 
and Baseline 
Characteristics 
• 
Added clarifying statements stating summaries “may be summarized.” 
Section 6.5 Extent of 
Exposure 
• 
Added description of “Relative Dose Intensity” 
• 
Updated definition of “Duration of Delays” to account for calculation of 
SPLIT and STRETCH dosing schedules. 
• 
Added description of “duration of follow-up” 
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RAP Section 
Amendment Details 
Section 7.1 Primary 
Efficacy Analyses 
• 
Added wording on summarizing 
 
• 
Deleted option to create ORR display at interim, based on unconfirmed 
responses in certain cases. ORR at interim analyses will be analyzed 
based on confirmed responses if available. 
• 
Updated “Derivation of Confirmed Response”, and “Assignments for 
Progression and Censoring Dates for 
& 
Analysis” tables to 
reflect format within latest Oncology RAP template. 
Section 7.2 Exploratory 
Efficacy Analyses 
Section 15.3.4 Extended 
Loss to Follow-up or 
Extended Time without an 
Adequate Assessment 
• 
Clarified definitions specific to Arms A and B.  
Section 15.4.2 Study 
Population  
• 
Replaced “randomized” with “enrolled in study” 
Section 15.12. Appendix 
12: List of Data Displays 
• 
Added description of “post-interim [1]” report, and updated descriptions of 
Interim [2] and Interim [3] in Section 15.12.2. 
• 
Made clarifying edits in titles/footnotes, programming notes, updates in 
delivery priority, and fixed typos in various displays to incorporate 
comments/decisions. 
• 
Programming note to add “Relative Dose Intensity” to Table 1.042 
(Summary of Exposure) 
• 
Deleted tables and listings related to summarizing ORR based on 
unconfirmed responses in certain cases. 
• 
Updated “Summary of Duration of Follow-up” (Tables 1.065/1.065), 
“Summary of Duration of Response” (Tables 2.009/2.010), “Summary of 
” (Tables 2.012/2.013), and “Summary of 
” (Tables 2.015/2.016) to be reported for both interim and 
SAC. 
• 
Added “Summary of Adverse Events” related to each specific study drug, 
as per ICH. 
• 
Prioritized different displays with respect to being observed at interim 
and/or SAC 
Section 15.13 Appendix 13: 
Example Mock Shells for 
Data Displays 
• 
Made clarifying edits in title/footnote, added content, and fixed typos in 
various mock shells to incorporate comments from dry run reviews. 
Statistical Analysis Plan RAP Amendment 2 [26-JUL-2022] 
Section 2 Summary of Key 
Protocol Information 
• 
Updated Summary of Key Protocol Information to be consistent with 
latest protocol amendment (Amendment 04) 
Section 2.1 Changes to the 
Protocol Defined Statistical 
Analysis Plan 
• 
Edited Table 1 to no longer include 
 and 
 
as they were both added to latest protocol amendment (Amendment 04). 
Section 3.2 Primary and 
• 
Updated definition of Final Analysis to be consistent with latest protocol 
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RAP Section 
Amendment Details 
Final Analyses 
amendment (Amendment 04) and add PACT language.  
Section 6.5 Extent of 
Exposure 
• 
Updated dose intensity and relative dose intensity (RDI) calculations with 
the following updates:  
o Split lenalidomide calculations into 25 mg vs. 10 mg. 
o No longer using “death date” as a potential end date. 
o Separate RDI calculations into Cycle 1 and Post-Cycle 1.  
Section 7.1 Primary 
Efficacy Analyses 
• 
Table 6: Add footnote to clarify how to handle Best Overall Response for 
subjects without adequate baseline data.  
Section 7.2 Exploratory 
Efficacy Analyses 
Section 8 Safety Analyses 
• 
Clarified the frequency and percentage of AEs (all grades) will be 
summarized and displayed in three ways: 1) in descending order of total 
incidence by PT only, 2) in descending order of total incidence by 
System Organ Classes (SOC) and PT, and 3) in descending order of 
total incidence by System Organ Classes (SOC) and PT and Maximum 
Grade. 
• 
Added a section to describe Anti-Drug Antibody Analyses to be 
performed at final SAC. 
Section 15.5.2.1 Handling 
of Missing Data 
• 
Deleted statement about the storage of imputed dates.  
Section 15.7.1 
Pharmacokinetic / 
Pharmacodynamic Dataset 
Specification 
• 
Added wording to guide exposure-response analysis. 
Section 15.11 
Abbreviations & 
Trademarks 
• 
Added relevant abbreviations 
Section 15.12. Appendix 
12: List of Data Displays 
• 
Updated Deliveries 
• 
Made clarifying edits in titles/footnotes, programming notes, updates in 
delivery priority, and fixed typos in various displays to incorporate 
comments/decisions. 
Statistical Analysis Plan RAP Amendment 3 [DD-MMM-2023] 
Various sections 
• 
Edited grammatical errors and/or typos 
Section 5.3.1 Examination 
of Subgroups 
• 
Added/Edited subgroup analyses and clarified wording/categories on 
existing subgroups 
Section 6.2 Disposition of 
Participants 
• 
Edited displays being produced to understand the impact of COVID 
Section 6.5 Extent of 
Exposure 
• 
Edited calculation of dose intensity and relative dose intensity of 
Dexamethasone 
Section 7.1.2 Summary 
Measure 
• 
Edited wording on subgroup analyses 
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RAP Section 
Amendment Details 
Section 13.1 Compliance of 
PRO-CTCAE, OSDI, and 
EORTC QLQ-C30 
• 
Corrected OSDI “summary” score to “total” score 
Section 13.3.2 Ocular 
Surface Disease Index 
• 
Edited summaries around OSDI score 
Section 15.5.2.1 Handling 
of Missing and Partial 
Dates 
• 
Added wording under partial dates for Concomitant Medications/ Blood 
Supportive Products 
Section 15.12.2 
• 
Added HDL RAPIDO deliveries 
Section 15.12. Appendix 
12: List of Data Displays 
• 
Added/Edited displays, and made clarifying edits in titles/footnotes, 
programming notes, updates in delivery priority, and fixed typos in 
various displays to incorporate comments/decisions. 
 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
Changes from the originally planned statistical analysis specified in the protocol are 
outlined in Table 1. 
Table 1 
Changes to Protocol Defined Analysis Plan 
Protocol 
Reporting & Analysis Plan 
Statistical Analysis Plan 
Statistical Analysis Plan 
Rationale for Changes 
• 
Overall Response Rate 
(ORR) is defined as a 
primary endpoint for Part 2 
under the assessment of 
clinical activity. 
• 
ORR will be calculated 
for participants within 
Part 1 and Part 2. 
• 
Protocol states “Data from Part 1 
and Part 2 may be combined at 
interim, primary, and final analyses” 
which includes observing ORR for 
Parts 1 and 2. 


 
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2.2. 
Study Objective(s) and Endpoint(s)  
Objectives 
Endpoints 
Primary 
Dose Escalation 
Determine safety, tolerability of belantamab 
mafodotin in combination with either Len/Dex 
(Arm A) or Bor/Dex (Arm B) to establish a 
recommended dose range and schedule to 
evaluate in Dose Expansion for participants with 
RRMM 
 
Dose Escalation and Expansiona 
Select the dose(s) and dosing schedule for 
further investigation based on safety and 
tolerability of belantamab mafodotin in 
combination with either Len/Dex (Arm A) or 
Bor/Dex (Arm B) for participants with RRMM     
 
Number (%) of participants with DLTs. 
Number (%) of participants with AEs, changes 
in clinical signs and laboratory parameters. 
 
 
 
A comprehensive determination based on 
safety and SAE/AEs. 
Dose Expansion 
To determine preliminary clinical activity of 
belantamab mafodotin in combination with either 
Len/Dex (Arm A) or Bor/Dex (Arm B) for 
participants with RRMM     
 
A specific determination based on ORR 
defined as percentage (%) of participants 
achieving PR as defined by the IMWG 
Uniform Response Criteria for MM [Kumar, 
2016]. 
Secondary 
Dose Escalation and Expansion 
To evaluate the pharmacokinetics profile of 
belantamab mafodotin when administered in 
combination with Len/Dex (Arm A) or Bor/Dex 
(Arm B) in participants with RRMM 
Belantamab mafodotin PK parameters, as 
data permit  
To evaluate the pharmacokinetics profile of 
lenalidomide when administered in combination 
with belantamab mafodotin and dexamethasone 
Lenalidomide PK parameters, as data permit 
in Cycle 1 
To evaluate the pharmacokinetics profile of 
bortezomib when administered in combination 
with belantamab mafodotin and dexamethasone 
Bortezomib PK parameters, as data permit in 
Cycle 1 
To assess anti-drug antibodies (ADAs) against 
belantamab mafodotin 
Incidence and titers of ADAs against 
belantamab mafodotin pre-dose in Cycle 1 
and selected subsequent cycles 
To evaluate the effect and tolerability of 
belantamab mafodotin in combination with 
Len/Dex (Arm A) or Bor/Dex (Arm B) on 
symptomatic adverse events in participants with 
Changes from baseline in symptoms and 
related impacts as measured by OSDI, NEI-
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Objectives 
Endpoints 
RRMM 
To further characterize safety of belantamab 
mafodotin administered in combination with 
Len/Dex (Arm A) or Bor/Dex (Arm B) in 
participants with RRMM 
Incidence of AEs, including SAEs and AEs of 
special interest (corneal events, 
thrombocytopenia and infusion related 
reactions). 
 
Ocular findings on ophthalmic exam 
To evaluate the effect of belantamab mafodotin in 
combination with Len/Dex (Arm A) or Bor/Dex 
(Arm B) on health-related quality of life in 
participants with RRMM 
Changes from baseline in health-related 
quality of life as measured by the EORTC 
QLQ-C30 and QLQ-MY20 
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Objectives 
Endpoints 
• Abbreviations: Len/Dex = Lenalidomide/Dexamethasone; Bor/Dex = 
Bortezomib/Dexamethasone; RRMM = Relapsed/Refractory Multiple Myeloma; DLT = Dose-
limiting toxicities; AE = Adverse Event; SAE = Serious Adverse Event; ORR = Overall 
Response Rate; PR = Partial Response; IMWG = International Myeloma Working Group; MM = 
Multiple myeloma; PK = Pharmacokinetic(s); OSDI = Ocular Surface Disease Index; NEI-VFQ-
25 = National Eye Institute 25-item Visual Function Questionnaire; PRO CTCAE =  Patient-
Reported Outcomes Version of the Common Term Criteria for Adverse Events; EORTC QLQ-
C30 = European Organization for Research and Treatment of Cancer Quality of Life 
Questionnaire 30-item Core module; QLQ-MY20 = European Organization for Research and 
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Objectives 
Endpoints 
Treatment of Cancer Quality of Life Questionnaire 20-item Multiple Myeloma module; 
 
; VGPR = Very Good Partial Response; BCMA = B-cell maturation 
antigen; 
; Cmax = Maximum plasma concentration; AUC = Area under 
the concentration time curve 
a. 
Data from the both the Escalation and Expansion cohorts will be used to evaluate this composite endpoint. 
 
 
2.3. 
Study Design 
2.3.1. 
Overall Design 
This is a Phase I/II, open-label, dose escalation and expansion study to select the dose 
and dosing schedule of belantamab mafodotin when given in combination with Len/Dex 
(Arm A) on a 28-day cycle, or with Bor/Dex (Arm B) on a 21-day cycle, and to evaluate 
safety and clinical activity of the combination treatments in participants with RRMM. 
The study will consist of two parts.  
Part 1 is a dose escalation phase to evaluate the safety and tolerability of belantamab 
mafodotin in combination with two SoC regimens: Arm A – belantamab mafodotin with 
Len/Dex, and Arm B – belantamab mafodotin with Bor/Dex. 
Part 2 is a dose expansion phase to further evaluate the safety and clinical activity of 
belantamab mafodotin in combination with Len/Dex (Arm A) and Bor/Dex (Arm B). 
 
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2.3.1.1. 
Arm A - Belantamab Mafodotin with Len/Dex 
Overview of Study Design and Key Features 
 
a. 
Belantamab mafodotin (GSK2857916) SINGLE = full assigned dose of belantamab mafodotin administered on Day 1 of 
any 28-day cycle. 
b. 
Lenalidomide (25 mg on Days 1-21) + Dexamethasone (40 mg on Days 1, 8, 15, and 22) of any 28-day cycle. 
c. 
Belantamab mafodotin 2.5 mg/kg SPLIT= 1.25 mg/kg on Day 1 and 1.25 mg/kg on Day 8 of any 28-day cycle. 
d. 
*Belantamab mafodotin 1.9 mg/kg STRETCH = belantamab mafodotin 1.9 mg/kg dose administered on Day 1 of 
alternate 28-day cycles i.e., Q8W (C1, C3, C5, C7 and so on)- this cohort may be evaluated if emerging data suggests 
that this schedule may further optimize the tolerability or offers an improved benefit/risk profile. 
All participants will be operated under Amendment 03. 
Note: Combination therapy continued until PD, death, intolerable toxicity, consent withdrawn. Cohorts followed up for 
 
and 
 DE = Dose Escalation decision. 
Design 
Features 
• 
Population: Adult participants with RRMM, who have undergone stem cell transplant (SCT), 
or are considered transplant ineligible, and who have been previously treated with at least 1 
prior line of therapy, and who have documented evidence of disease progression during or 
after their most recent therapy. 
 
• 
Objective: Part 1 is a dose escalation phase to evaluate the safety and tolerability of 
belantamab mafodotin in combination with Len/Dex. Part 2 is a dose expansion phase to 
further evaluate the safety and clinical activity of belantamab mafodotin in combination with 
Len/Dex. 
Dosing 
• 
SINGLE Dosing Schedule: belantamab mafodotin will be administered as a SINGLE full 
dose on Day 1 of each 28-day cycle. 
 
• 
SPLIT Dosing Schedule: belantamab mafodotin will be split into two equal halves and each 
half dose will be administered on Day 1 and Day 8 of each 28-day cycle. 
 
• 
STRETCH Dosing Schedule: A STRETCH dosing schedule for the 1.9 mg/kg dose level 
might be considered for Arm A if emerging data suggests that this schedule may further 
optimize the tolerability or offers an improved benefit/risk profile. In STRETCH schedule, 
belantamab mafodotin will be administered on Day 1 of alternate 28-day cycles with any 2 
consecutive planned belantamab mafodotin doses at least 56 (±3) days apart. The 
treatment cycle duration will remain at 28 days (4 weeks). 
 
• 
Summary of Treatment Regimens and Schedules for Len/Dex are provided in Table 18 of 
the Protocol (Version: GSK Document Number TMF-14624358). 
Time & 
Events 
• 
Refer to Section 3 of Protocol – Schedule of Activities (Version: GSK Document Number 
TMF-14624358) 
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Overview of Study Design and Key Features 
Treatment 
Assignment 
• 
This is a non-randomized, double-arm, open label, two-part study 
Interim 
Analysis 
• 
Part 1: Dose Escalation 
o No formal interim analysis is planned for Part 1. Data will be reviewed through data 
visualization tools to inform dose escalation decisions. The modified Toxicity Probability 
Interval (mTPI) design will be utilized to guide dose escalation/de-escalation decisions. 
mTPI is explained in Section 3.1.1.1. 
 
• 
Part 2: Dose Expansion 
o An interim analysis may be conducted when the last participant within each arm is 
followed for at least 1 cycle to evaluate safety, efficacy, and PK profiles at each dose 
level. Following the interim analysis, additional analyses may be performed to continue 
to evaluate safety, efficacy, and PK profiles at each dose level, prior to the primary and 
final analyses. If any dose level is not enrolled due to safety concerns, it will not be 
included in the interim or final analyses. Additionally, if enrollment is stopped within a 
dose group, data may be analyzed for participants within the dose group who take at 
least 1 dose of any study treatment.  
 
o Continuous monitoring will be conducted for Part 2 starting from when 5 participants 
are dosed at each dose level within each arm. The observed number of participants 
permanently discontinuing study treatment within the first two cycles due to AE related 
to belantamab mafodotin will be compared against the safety stopping rule in Table 30 
of the Protocol (Version: GSK Document Number TMF-14624358). Enrollment may 
stop if the safety stopping rule is met based on totality of safety data. For example, if 4 
or more out of 5 participants permanently discontinued study treatment within the first 2 
cycles due to AE related to belantamab mafodotin, enrollment may stop after review of 
all safety data; otherwise, enrollment will continue. 
 


 
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2.3.1.2. 
Arm B - Belantamab Mafodotin with Bor/Dex 
Overview of Study Design and Key Features 
 
a. 
Belantamab mafodotin (GSK2857916) SINGLE = full assigned dose of belantamab mafodotin (1.9 mg/kg, 2.5 mg/kg, 
or 3.4 mg/kg) administered on Day 1 of any 21-day cycle. 
b. 
Bortezomib (1.3 mg/m2 on Days 1, 4, 8, and 11) + Dexamethasone (20 mg on Days 1, 2, 4, 5, 8, 9, 11, and 12) of any 
21-day cycle. 
c. 
Belantamab mafodotin 2.5 mg/kg SPLIT= 1.25 mg/kg on Day 1 and 1.25 mg/kg on Day 8 of any 21-day cycle. 
d. 
Belantamab mafodotin 3.4 mg/kg SPLIT= 1.7 mg/kg on Day 1 and 1.7 mg/kg on Day 8 of any 21-day cycle. 
e. 
Belantamab mafodotin STRETCH= belantamab mafodotin 1.9 mg/kg or 2.5 mg/kg dose administered on Day 1 of 
alternate 21-day cycles i.e., Q6W (C1, C3, C5, C7 and so on). 
f. 
Belantamab mafodotin Step-Down (S/D) STRETCH = belantamab mafodotin 2.5 mg/kg dose at C1D1 followed by 1.9 
mg/kg step-down dose on Day 1 of alternate 21-day cycles C3 onwards (C3, C5, C7, and so on). 
All participants will be operated under Amendment 03.  
#New cohorts in Amendment 3. 
Note: Combination therapy continued for up to 8 combination cycles; belantamab mafodotin further continued until PD, 
death, intolerable toxicity, consent withdrawn. Cohorts followed up for 
and 
 
DE=Dose Escalation decision; 
; PD=Progressive Disease; 
 S/D=Step-
down. 
Design 
Features 
• 
Population: Adult participants with RRMM, who have undergone stem cell transplant 
(SCT), or are considered transplant ineligible, and who have been previously treated with 
at least 1 prior line of therapy, and who have documented evidence of disease progression 
during or after their most recent therapy. 
 
• 
Objective: Part 1 is a dose escalation phase to evaluate the safety and tolerability of 
belantamab mafodotin in combination with  Bor/Dex. Part 2 is a dose expansion phase to 
further evaluate the safety and clinical activity of belantamab mafodotin in combination with 
Bor/Dex. 
Dosing 
• 
SINGLE Dosing Schedule: belantamab mafodotin will be administered as a SINGLE full 
dose on Day 1 of each 21-day cycle. 
 
• 
SPLIT Dosing Schedule: belantamab mafodotin will be split into two equal halves and 
each half dose will be administered on Day 1 and Day 8 of each 21-day cycle. 
 
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Overview of Study Design and Key Features 
• 
STRETCH Dosing Schedule: belantamab mafodotin will be administered on Day 1 of 
alternate cycles with any two consecutive planned doses at least 42 (3) days apart. The 
treatment cycle duration will remain at 21 days (3 weeks). 
 
• 
Step-Down (S/D) STRETCH Dosing Schedule: belantamab mafodotin will be administered 
as a full 2.5 mg/kg dose on Day 1 of Cycle 1 followed by subsequent planned doses of 1.9 
mg/kg S/D dose starting on Day 1 of alternate 21-day cycles (C3, C5, C7, and so on) with 
any two consecutive planned doses at least 42 (3) days apart. The treatment cycle 
duration will remain at 21 days (3 weeks). 
 
• 
Summary of Treatment Regimens and Schedules for Bor/Dex are provided in Table 18 of 
the Protocol (Version: GSK Document Number TMF-14624358). 
Time & 
Events 
• 
Refer to Section 3 of Protocol – Schedule of Activities (Version: GSK Document Number 
TMF-14624358) 
Treatment 
Assignment 
• 
This is a non-randomized, double-arm, open label, two-part study 
Interim 
Analysis 
• 
Part 1: Dose Escalation 
o No formal interim analysis is planned for Part 1. Data will be reviewed through data 
visualization tools to inform dose escalation decisions. The modified Toxicity 
Probability Interval (mTPI) design will be utilized to guide dose escalation/de-
escalation decisions. mTPI is explained in Section 3.1.1.1. 
 
• 
Part 2: Dose Expansion 
o An interim analysis may be conducted when the last participant within each arm is 
followed for at least 1 cycle to evaluate safety, efficacy, and PK profiles at each dose 
level. Following the interim analysis, additional analyses may be performed to 
continue to evaluate safety, efficacy, and PK profiles at each dose level, prior to the 
primary and final analyses. If any dose level is not enrolled due to safety concerns, it 
will not be included in the interim or final analyses. Additionally, if enrollment is 
stopped within a dose group, data may be analyzed for participants within the dose 
group who take at least 1 dose of any study treatment.  
 
o Continuous monitoring will be conducted for Part 2 starting from when 5 participants 
are dosed at each dose level within each arm. The observed number of participants 
permanently discontinuing study treatment within the first two cycles due to AE related 
to belantamab mafodotin will be compared against the safety stopping rule in Table 30 
of the Protocol (Version: GSK Document Number TMF-14624358). Enrollment may 
stop if the safety stopping rule is met based on totality of safety data. For example, if 4 
or more out of 5 participants permanently discontinued study treatment within the first 
2 cycles due to AE related to belantamab mafodotin, enrollment may stop after review 
of all safety data; otherwise, enrollment will continue. 
 


 
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2.4. 
Statistical Hypotheses / Statistical Analyses 
2.4.1. 
Arm A - Belantamab Mafodotin with Len/Dex 
2.4.1.1. 
Part 1 Dose Escalation 
No formal statistical hypotheses are being tested in Part 1. Analysis of the data obtained 
from Part 1 will only utilize descriptive methods. 
2.4.1.2. 
Part 2 Dose Expansion 
No formal statistical hypotheses are being tested in Part 2. Analysis of the data obtained 
from Part 2 will only utilize descriptive methods. 
For Part 2, the number of participants who permanently discontinue study treatment due 
to AEs related to belantamab mafodotin within the first two cycles will be continuously 
monitored. For STRETCH dosing schedule, a cycle is a SoC cycle of 28 days. If the 
observed number of participants permanently discontinuing belantamab mafodotin is 
significantly higher than 12% (at 1-sided alpha of 0.01), then the combination treatment 
at that dose level or higher dose level will be considered to have unacceptable toxicity 
and the dose level as well as higher dosed levels will be closed. 
2.4.2. 
Arm B - Belantamab Mafodotin with Bor/Dex 
2.4.2.1. 
Part 1 Dose Escalation 
No formal statistical hypotheses are being tested in Part 1. Analysis of the data obtained 
from Part 1 will only utilize descriptive methods. 
2.4.2.2. 
Part 2 Dose Expansion 
No formal statistical hypotheses are being tested in Part 2. Analysis of the data obtained 
from Part 2 will only utilize descriptive methods. 
For Part 2, the number of participants who permanently discontinued study treatment due 
to AEs related to belantamab mafodotin within the first two cycles will be continuously 
monitored starting from when 5 participants are dosed. For STRETCH dosing schedule, a 
cycle is a SoC cycle of 21 days. If the observed number of participants permanently 
discontinuing belantamab mafodotin is significantly higher than 12% (at 1-sided alpha of 
0.01), then the combination treatment at that dose level or higher dose level will be 
considered to have unacceptable toxicity and the dose level as well as higher dose levels 
will be closed. 
 


 
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3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
3.1.1. 
 Arm A – Belantamab Mafodotin with Len/Dex 
3.1.1.1. 
Part 1 Dose Escalation 
During dose escalation, no formal interim analysis will be performed. Data will be 
reviewed through data visualization tool to inform dose escalation decisions. The mTPI 
design will be utilized to guide dose escalation/de-escalation decisions. More details of 
the dose escalation procedure are described below. 
Description of the Modified Toxicity Probability Interval 
The modified Toxicity Probability Interval (mTPI) design [Ji, 2010] will be used to guide 
dose escalation in Part 1 with a slight modification. Up to 2 dose levels of belantamab 
mafodotin (1.9 mg/kg [dose -1]; 2.5 mg/kg [dose 1]) and alternate dosing schedules are 
planned to be evaluated in combination with the fixed dose of the Len/Dex treatments. 
Based on emerging data under Protocol Amendment 1 from Arm A, the first dose 
investigated under Protocol Amendment 2 was 1.9 mg/kg (Dose Level -1). The design 
assumes the true underlying toxicity rate for maximum tolerated dose (MTD) of 
belantamab mafodotin falls within the range from 25% to 35% and centers at 30%. The 
rules for guiding dose escalations are provided in Figure 1. Columns provide the numbers 
of participants treated at the current dose level, and rows provide the corresponding 
numbers of participants experiencing toxicity. Cohorts will be recruited in blocks of three 
participants. Participants will be treated in a staggered approach with at least 1 day 
between each participant’s first dose of belantamab mafodotin to minimize the risk of 
inadvertently exceeding the MTD in multiple participants.  
In Part 1 up to 2 dose levels of belantamab mafodotin and up to 2 dosing schedules will 
be evaluated (Figure 1 and Table 2). Data from at least 3 DLT-evaluable participants are 
required before a decision is made to escalate to the next dose level. However, this is not 
required for enrollment of more participants at the same dose level in Part 2. 
 


 
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Figure 1 
Dose-finding Criteria for the Modified Toxicity Probability Interval 
(mTPI) Dose-Finding Method 
Number of DLTs 
Number of Participants treated at current dose 
1 
2 
3 
4 
5 
6 
0 
E 
E 
E 
E 
E 
E 
1 
D 
S 
S 
S 
S 
E 
2 
DU 
D 
S 
S 
S 
3 
DU 
DU 
D 
S 
4 
DU 
DU 
DU 
5 
DU 
DU 
6 
DU 
The spreadsheet was generated based on a beta/binomial model and precalculated before trial initiation. The letters in 
different colors are computed based on the decision rules under the mTPI method and represent different dose-finding 
actions. In addition to actions de-escalate the dose (D), stay at the same dose (S), and escalate the dose (E), the table 
includes action unacceptable toxicity (DU), which is defined as the execution of the dose-exclusion rule in mTPI. 
Excerpted from Ji, et al. [Ji, 2010]. 
The entries of Figure 1 are dose-finding decisions (i.e., E, S, and D) representing 
escalating the dose, staying at the same dose, and de-escalating the dose. In addition, 
decision DU means that the current dose level is unacceptable because of high toxicity; 
the current dose level and any higher dose level should be excluded from the trial.  
 
For example, when 1 of 3 participants experiences toxicity, the decision can be located at 
row 1 and column 3, which is S – to stay at the current dose level. Consequently, the next 
cohort of participants will be treated at the same dose level currently being used. If zero 
of three participants experience toxicity, the decision is at row 0 and column 3, which is 
E – to escalate. Thus, the next cohort of participants will be treated at the next-higher 
dose level. If 3 of 3 participants experience toxicity, the decision is DU – to de-escalate to 
the next-lower dose level and exclude the current dose and any higher dose from the trial, 
because toxicity levels are unacceptable. In dose escalation (E)/de-escalation (D), no dose 
skipping is allowed. 
 
Table 2 
Dose Levels: Arm A, Part 1 
Treatment Group 
and Dose Level 
Belantamab Mafodotin 
Lenalidomide 
Dexamethasone 
Permissible Actions 
Increase/Decrease 
No changes 
No changes 
Dose Level -1 
(de-escalation) 
1.9 mg/kg IV q28 days 
25 or 10 mg PO, QD on 
Days 1 to 21 of each 28-
day cycle 
40 or 20 mg/week PO or 
IV on Days 1, 8, 15, and 
22 of each 28-day cycle 
Dose Level 1 
2.5 mg/kg IV q28 daysa 
25 or 10 mg PO, QD on 
Days 1 to 21 of each 28-
day cycle 
40 or 20 mg/week PO or 
IV on Days 1, 8, 15, and 
22 of each 28-day cycle 
IV = intravenous; PO = orally; QD = once daily; SC = subcutaneous 
a. 
Alternate dosing schedule could be investigated such as 2.5 mg/kg SPLIT dosing schedule where belantamab 
mafodotin will be administered at 1.25 mg/kg each on Day 1 and Day 8 
 


 
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Any participant from Part 1 in Arm A who received at least 1 full dose of belantamab 
mafodotin and at least 75% of planned doses of Len/Dex by the end of Cycle 1 (Day 28 
for Arm A) is considered DLT-evaluable. Participants in Part 1 who have received less 
than 1 full dose of belantamab mafodotin, or <75% of planned doses of Len/Dex, or who 
have been withdrawn from the study for reasons other than toxicity but prior to 
completion of DLT observation period will be replaced. 
Part 1 starts with a cohort of 3 participants at a dose level of 1.9 mg/kg SINGLE. Safety 
data over the first cycle of treatment for each participant will be evaluated. Data from at 
least 3 DLT evaluable participants are required before a decision is made to escalate to 
the next dose level. The study will enroll participants in Part 1 will have staggered start 
times, but will run simultaneously as outlined below. If dose levels are open for both Part 
1 and Part 2, priority for enrollment will be given to Part 1. 
Rules for of mTPI dose escalation pertaining to Arm A only: 
• If dose escalation decision is E, enrollment for Part 1 will be open at 2.5 mg/kg 
SINGLE and 2.5 mg/kg SPLIT. At the same time, Part 2 expansion could be 
opened to enroll additional participants at 1.9 mg/kg SINGLE. 
• If dose escalation decision is S, three additional participants will be enrolled at 
1.9 mg/kg SINGLE in Part 1 to achieve at least 6 DLT-evaluable participants at 
1.9 mg/kg SINGLE. After review of data from the 6 participants: 
o If dose escalation decision is E, 2.5 mg/kg SINGLE and 2.5 mg/kg SPLIT 
will be open for enrollment in Part 1. Part 2 expansion will not be open for 
the 1.9 mg/kg SINGLE dose level unless emerging data suggest 2.5 mg/kg 
SINGLE and 2.5mg/kg SPLIT are not tolerable. 
o If dose escalation decision is S, enrollment will not open for dose levels 
higher than 1.9 mg/kg SINGLE in Part 1. Part 2 expansion will be open to 
enroll additional participants at 1.9 mg/kg SINGLE.  
o If dose escalation decision is D or DU, no more participants will be 
enrolled at 1.9 mg/kg SINGLE or higher dose levels in Part 1.  
Once the 2.5 mg/kg SINGLE and 2.5 mg/kg SPLIT cohorts are open for enrollment in 
Part 1, a cohort of at least 3 participants will be enrolled for each dose. When Part 1 is 
filled, Part 2 expansion will open for enrollment at 2.5 mg/kg SINGLE and 2.5 mg/kg 
SPLIT. Data from at least 6 DLT-evaluable participants at 2.5 mg/kg SINGLE and 2.5 
mg/kg SPLIT are not required for enrollment of additional participants in Part 2. 
 


 
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Operating characteristics of the dose escalation rules are shown in Table 3. 
Table 3 
Operating Characteristics of the Dose Escalation Rules for Arm A 
 
Underlying True Toxicity Rate 
Average n. of participants dosed at each dose 
level1 
Prob. of Selecting as MTD2 
Scenario 
1.9 SINGLE 
2.5 SPLIT 
2.5 SINGLE 
1.9 SINGLE3 
2.5 SPLIT 
2.5 SINGLE 
<1.9 
1.9 SINGLE 
2.5 SINGLE / 
2.5 SPLIT 
1 
0.2 
0.30 
0.30 
11 
9 
9 
0.11 
0.23 
0.66 
2 
0.2 
0.30 
0.35 
11 
9 
9 
0.11 
0.25 
0.64 
3 
0.2 
0.40 
0.40 
11 
8 
8 
0.11 
0.31 
0.58 
4 
0.2 
0.40 
0.45 
11 
9 
9 
0.11 
0.34 
0.56 
5 
0.3 
0.40 
0.40 
10 
6 
6 
0.23 
0.37 
0.40 
6 
0.3 
0.40 
0.45 
10 
6 
6 
0.23 
0.38 
0.39 
7 
0.1 
0.30 
0.30 
12 
11 
11 
0.03 
0.13 
0.84 
8 
0.1 
0.25 
0.30 
12 
11 
11 
0.03 
0.11 
0.86 
9 
0.1 
0.25 
0.25 
12 
11 
11 
0.03 
0.10 
0.87 
10 
0.1 
0.20 
0.20 
12 
11 
11 
0.03 
0.08 
0.89 
11 
0.1 
0.20 
0.25 
12 
11 
11 
0.03 
0.09 
0.88 
Bold: Dose too toxic/n of participants exposed to a toxic dose/prob. of selecting toxic dose as MTD 
Italicized: True MTD dose/prob. of selecting true MTD as MTD 
1. 
Average n. of participants dosed at each dose level include n. of participants dosed in Part 2 assuming participants for each dose level in Part 2 are enrolled before dose 
escalation decision is made in Part 1, except for dose 1.9 mg/kg, for which Part 2 will not open for enrollment prior to dose escalation decision. 
2. 
Based on participants enrolled in Part 1 and assume the underlying true MTD is 30%. 
3. 
Number in this column represents maximum estimate where dose is escalated to 2.5 mg/kg but is de-escalated to 1.9 mg/kg based on Part 1 and Part 2 data from 2.5 mg/kg. 


 
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Dose Escalation Decisions 
During Part 1, the decisions on dose escalation will be made based on the mTPI 
guidance, as well as the totality of the safety, and pharmacokinetics data as appropriate. 
The decisions will occur following review of all available data including participants data 
from Part 2 and joint discussion by the GSK medical monitor, participating investigators, 
and others as described in the Dose Escalation Plan. 
The GSK study team, which includes but is not limited to, the GSK medical monitor, 
clinical scientist, safety physician, statistician, and clinical pharmacologist, will review 
critical safety data defined in the Dose Escalation Plan prior to making a recommendation 
for dose escalation. This includes review of all adverse events including non-DLT 
toxicities, laboratory assessments and other defined safety evaluations, as well as PK 
and/or PD data, when appropriate. The results from the mTPI method will be included in 
the decision for dose modification as described in Section 12.4.8 of the Protocol 
(Version: GSK Document TMF-14624358). Quality control of critical safety data will be 
described in the Dose Escalation Plan, which includes ongoing study monitoring visits, 
GSK review of the clinical database, and confirmation by participating investigators 
and/or delegate that the data are accurate and complete prior to making dose modification 
decisions. 
The GSK medical monitor, in joint discussion with participating investigators, and others 
as described in the Dose Escalation Plan will be responsible for making dose escalation 
decisions. The dose-escalation decision and rationale for each cohort will be discussed 
with investigators during teleconference(s) and documented in writing, with copies 
maintained at each study site and in the study master file. 
3.1.1.2. 
Part 2 Dose Expansion 
Once Part 2 expansion is open for the 2.5 mg/kg SINGLE and 2.5 mg/kg SPLIT dose 
levels, up to 9 participants will be enrolled at each dosing schedule, unless enrollment is 
stopped based on emerging data. 
In addition, up to 12 more participants maybe potentially enrolled to evaluate an extended 
(STRETCH) dosing schedule for belantamab mafodotin at the 1.9 mg/kg dose level if 
emerging data suggests that this schedule may further optimize the tolerability or offers 
an improved benefit/risk profile. 
For STRETCH Dosing Schedule, belantamab mafodotin will be administered FIRST 
(prior to Len/Dex) as a single dose on Day 1 of every alternate 28-day cycle (C1, C3, C5, 
C7 and so on) as a 30-60 min infusion, followed by 1 to 2 h rest period. If a planned dose 
of belantamab mafodotin was held/missed due to any reason, the next dose can be 
administered at Day 1 of the next planned 28-day cycle, as long as the interval between 2 
consecutive doses is at least 56 (3) days.  
Safety data from all enrolled participants will be closely monitored while the study is 
ongoing. In addition, participants permanently discontinuing study treatment within the 
first two cycles due to AEs related to belantamab mafodotin will be continuously 
monitored starting from when 5 participants are dosed at each dose level following pre- 


 
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defined safety stopping rules (Section 12.4.8.1 of the Protocol –Version: GSK Document 
TMF-14624358). If safety concerns arise at a dose level, enrollment will stop for that 
dose level and higher dose level(s). 
Safety Stopping Rule 
Continuous monitoring will be conducted for Part 2 starting from when 5 participants are 
dosed at each dose level within each arm. The observed number of participants 
permanently discontinuing study treatment within the first two cycles due to AE related 
to belantamab mafodotin will be compared against the safety stopping rule in Table 4. 
Enrollment may stop if the safety stopping rule is met based on totality of safety data. For 
example, if 4 or more out of 5 participants permanently discontinued study treatment 
within the first 2 cycles due to AE related to belantamab mafodotin, enrollment may stop 
after review of all safety data; otherwise, enrollment will continue. Operating 
characteristics for the stopping rule are provided in Figure 2. 
Table 4 
Safety Stopping Rules for Part 2 
Number of dosed 
participants 
Stop if number of 
participants discontinuing 
study treatment within the 
first two cycles due to AE 
related to belantamab 
mafodotin is larger or equal 
to this number 
Observed Rate 
5-8 
4 
0.5-0.8 
9-12 
5 
0.42-0.56 


 
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Figure 2 
Operating Characteristics of Safety Stopping Rule for Expansion 
Cohort 
 
An interim analysis may be conducted when the last participant within each arm is 
followed for at least 1 cycle to evaluate safety, efficacy, and PK profiles at each dose 
level. Following the interim analysis, additional analyses may be performed to continue 
to evaluate safety, efficacy, and PK profiles at each dose level, prior to the primary and 
final analyses. If any dose level is not enrolled due to safety concerns, it will not be 
included in the interim or final analyses. Additionally, if enrollment is stopped within a 
dose group, data may be analyzed for participants within the dose group who take at least 
1 dose of any study treatment.  
3.1.2. 
Arm B- Belantamab Mafodotin with Bor/Dex 
3.1.2.1. 
Part 1 Dose Escalation Phase 
During dose escalation, no formal interim analysis will be performed. Data will be 
reviewed through the data visualization tool to inform dose escalation decisions. The 
mTPI design will be utilized to guide dose escalation/de-escalation decisions. More 
details of the dose escalation procedure are described below. 
Description of the Modified Toxicity Probability Interval 
An mTPI design will be implemented [Ji, 2010] to guide dose escalation in Part 1. Up to 
3 dose levels of belantamab mafodotin (2.5 mg/kg [dose 1]; 3.4 mg/kg [dose +1]; 1.9 
mg/kg [dose -1]), starting with 2.5 mg/kg, are planned to be evaluated in combination 


 
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with the fixed dose of Bor/Dex. Cohorts will be recruited in blocks of three participants. 
Participants will be entered in a staggered approach with at least 1 day between each 
participant’s first dose of belantamab mafodotin to minimize the risk of inadvertently 
exceeding the maximum tolerated dose (MTD) in multiple participants. A maximum of 6 
participants will be assigned to each dose (Table 5). 
Table 5 
Dose Levels: Arm B, Part 1 
Treatment Group 
and Dose Level 
Belantamab Mafodotin 
Bortezomib 
Dexamethasone 
Permissible Actions 
Increase/Decrease 
No changes 
No changes 
Dose Level -1 
(de-escalation) 
1.9 mg/kg IV q21 days 
1.3 mg/m2 SC/IV on Days 
1, 4, 8, and 11 of every 
21-day cycle for a total 
up to 8 cycles 
20 mg PO or IV on Days 
1, 2, 4, 5, 8, 9, 11, and 12 
of every 21-day cycle for 
a total of up to 8 cycles. 
Dose Level 1 
Cohort 
2.5 mg/kg IV q21 daysa 
1.3 mg/m2 SC/IV on Days 
1, 4, 8, and 11 of every 
21-day cycle for a total 
up to 8 cycles 
20 mg PO or IV on Days 
1, 2, 4, 5, 8, 9, 11, and 12 
of every 21-day cycle for 
a total of up to 8 cycles. 
Dose Level +1 
Cohort 
3.4 mg/kg IV q21 daysb 
1.3 mg/m2 SC/IV on Days 
1, 4, 8, and 11 of every 
21-day cycle for a total 
up to 8 cycles 
20 mg PO or IV on Days 
1, 2, 4, 5, 8, 9, 11, and 12 
of every 21-day cycle for 
a total of up to 8 cycles. 
IV = intravenous; PO = orally; QD = once daily; SC = subcutaneous 
a. 
Alternate dosing schedule could be investigated such as SPLIT dosing schedule where belantamab mafodotin will 
be administered at 1.25 mg/kg each on Day 1 and Day 8 
b. 
Alternate dosing schedule could be investigated such as SPLIT dosing schedule where belantamab mafodotin will 
be administered at 1.7 mg/kg each on Day 1 and Day 8 
 
Evaluation of the available safety data over the first cycle of treatment for each 
participant enrolled in that dose level is required from at least 3 participants before a 
decision is made to enroll additional participants at the same or the subsequent dose level. 
However, this is not required for enrollment of more participants at the same dose level in 
Part 2. 
An additional dose level -1 of 1.9 mg/kg may be evaluated in case the starting dose of 
2.5 mg/kg is considered not tolerated.  
Rules for mTPI dose escalation pertaining to Arm B only: 
• If 2.5 mg/kg is the current dose level and the decision is S, and if less than 6 
participants have been evaluated for DLT and the planned maximum sample size is 
not reached, an additional cohort of 3 participants will be enrolled for DLT 
evaluation. If the dose escalation decision is S after this additional cohort, dose 
escalation is complete. 
• If 2.5 mg/kg is the current dose level and the decision is U or DU, additional lower 
dose (e.g., 1.9 mg/kg) may be explored. If the dose of 1.9 mg/kg is not tolerated (i.e., 
results in excessive toxicity) the trial will be terminated early for lack of tolerability.  


 
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• If 3.4 mg/kg is the current dose level and the decision is E or S, and if less than 6 
participants have been evaluated for DLT at the current dose, and the planned 
maximum sample size is not reached, an additional cohort of 3 participants will be 
evaluated for DLT at the current dose. If dose escalation is E or S after this additional 
cohort, dose escalation is complete.  
• Otherwise, the dose escalation will continue until the planned maximum sample size 
(12 DLT-evaluable participants for each treatment) is reached. At the end of dose 
escalation, the rule proposed by Ji, et al. [Ji, 2010] used to guide the selection of the 
estimated MTD, from dose levels at which 3 or more participants have been evaluated 
for DLT. 
During Part 1, the decisions on dose escalation will be made based on this guidance, as 
well as the totality of the safety, and pharmacokinetics data as appropriate.  
The decisions will occur following review of these data and joint discussion by the GSK 
medical monitor, participating investigators, and others as described in the Dose 
Escalation Plan. 
Any participant in Arm B who received at least 1 full dose of belantamab mafodotin and 
75% of planned doses of Bor/Dex by the end of Cycle 1 (Day 21) will be evaluated for 
DLTs. Participants who have received less than 1 full dose of belantamab mafodotin, or 
<75% of planned doses of Bor/Dex, or who have been withdrawn from the study for 
reasons other than toxicity but prior to completion of DLT observation period will be 
replaced. 
The dose escalation of belantamab mafodotin will not include doses higher than 3.4 
mg/kg. 
Dose Escalation Decisions 
The GSK study team, which includes but is not limited to, the GSK medical monitor, 
clinical scientist, safety physician, statistician, and clinical pharmacologist, will review 
critical safety data defined in the Dose Escalation Plan prior to making a recommendation 
for dose escalation. This includes review of all adverse events including non-DLT 
toxicities, laboratory assessments and other defined safety evaluations, as well as PK 
and/or PD data, when appropriate. The results from the mTPI method will be included in 
the decision for dose modification. Quality control of critical safety data will be described 
in the Dose Escalation Plan, which includes ongoing study monitoring visits, GSK review 
of the clinical database, and confirmation by participating investigators and/or delegate 
that the data are accurate and complete prior to making dose modification decisions. 
The GSK medical monitor, in joint discussion with participating investigators and GSK 
study team, will be responsible for making dose escalation decisions. The dose escalation 
decision and rationale for each cohort will be discussed with investigators during 
teleconference(s) and documented in writing, with copies maintained at each study site 
and in the study master file. 


 
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3.1.2.2. 
Part 2 Dose Expansion Phase 
In Part 2 enrollment will proceed in multiple expansion cohorts to further evaluate the 
safety profile and to evaluate the preliminary clinical activity of belantamab mafodotin in 
combination with Bor/Dex at 3 dose levels and 4 dosing schedules (2.5 mg/kg SPLIT, 2.5 
mg/kg SINGLE, 3.4 mg/kg SPLIT, 3.4 mg/kg SINGLE, 2.5 mg/kg STRETCH, S/D 
STRETCH, 1.9 mg/kg SINGLE and 1.9 mg/kg STRETCH).  
In Amendment 2, enrollment of each cohort was conducted by blocks of 3 participants 
each at 2.5 mg/kg SPLIT, 2.5 mg/kg SINGLE, 3.4 mg/kg SPLIT, and 3.4 mg/kg SINGLE 
with Bor/Dex for up to 12 participants each at 2.5 mg/kg SPLIT, 2.5 mg/kg SINGLE, 3.4 
mg/kg SPLIT and up to 9 participants at 3.4 mg/kg SINGLE.  
Similarly, in Amendment 3, enrollment of each cohort will be conducted by blocks of 3 
participants each in 2.5 mg/kg STRETCH, S/D STRETCH, 1.9 mg/kg SINGLE and 1.9 
mg/kg STRETCH, until approximately 12 participants are enrolled in each cohort.  
For the SINGLE dosing schedule, belantamab mafodotin will be administered as a 
SINGLE full dose on Day 1 of each 21-day cycle. For example: A “3.4 mg/kg SINGLE” 
dosing schedule will administer a 3.4 mg/kg dose on Day 1 of each cycle. A 2.5 mg/kg 
SINGLE dosing schedule of belantamab mafodotin will administer a 2.5 mg/kg dose on 
Day 1 of each cycle. A 1.9 mg/kg SINGLE dosing schedule of belantamab mafodotin 
will administer a 1.9 mg/kg dose on Day 1 of each cycle 
For the SPLIT dosing schedule, belantamab mafodotin will be split into two equal halves 
and each half dose will be administered on Day 1 and Day 8 of each 21-day cycle. For 
example: A “2.5 mg/kg SPLIT” dosing schedule will administer a 1.25 mg/kg dose on 
Day 1 and a 1.25 mg/kg dose on Day 8 of each cycle. A “3.4 mg/kg SPLIT” dosing 
schedule will administer a 1.7 mg/kg dose on Day 1 and a 1.7 mg/kg dose on Day 8 of 
each cycle. 
For STRETCH Dosing Schedule, belantamab mafodotin will be administered FIRST 
(prior to Bor/Dex) as a single dose on Day 1 of every alternate 21-day cycle (C1, C3, C5, 
C7 and so on) as a 30-60 min infusion, followed by 1 to 2 h rest period. If a planned dose 
of belantamab mafodotin was held/missed due to any reason, the next dose can be 
administered at Day 1 of the next planned 21-day cycle, as long as the interval between 2 
consecutive doses is at least 42 (3) days.  
For the S/D STRETCH schedule, belantamab mafodotin will be administered FIRST 
(prior to Bor/Dex) as a 2.5 mg/kg dose on Day 1 of Cycle 1, followed by 1.9 mg/kg S/D 
dose on Day 1 of all subsequent alternate 21-day cycles (C3, C5, C7 and so on), as a 30-
60 min infusion, followed by 1 to 2 h rest period.  
Safety data from all enrolled participants will be closely monitored while the study is 
ongoing. In addition, participants permanently discontinuing study treatment within the 
first two cycles due to AEs related to belantamab mafodotin will be continuously 
monitored starting from when 5 participants are dosed at each dose level following pre-
defined safety stopping rules (Section 12.4.8.2 of the Protocol –Version: GSK Document 


 
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TMF-14624358). If safety concerns arise at a dose level, enrollment will stop for that 
dose level and higher dose level(s).  
Safety Stopping Rule 
Continuous monitoring will be conducted for Part 2 starting from when 5 participants are 
dosed at each dose level within each arm. The observed number of participants 
permanently discontinuing study treatment within the first two cycles due to AE related 
to belantamab mafodotin will be compared against the safety stopping rule in Table 4. 
Enrollment may stop if the safety stopping rule is met based on totality of safety data. For 
example, if 4 or more out of 5 participants permanently discontinued study treatment 
within the first 2 cycles due to AE related to belantamab mafodotin, enrollment may stop 
after review of all safety data; otherwise, enrollment will continue. Operating 
characteristics for the stopping rule are provided in Figure 2. 
An interim analysis may be conducted when the last participant within each arm is 
followed for at least 1 cycle to evaluate safety, efficacy, and PK profiles at each dose 
level. Following the interim analysis, additional analyses may be performed to continue 
to evaluate safety, efficacy, and PK profiles at each dose level, prior to the primary and 
final analyses. If any dose level is not enrolled due to safety concerns, it will not be 
included in the interim or final analyses. Additionally, if enrollment is stopped within a 
dose group, data may be analyzed for participants within the dose group who take at least 
1 dose of any study treatment. 
3.2. 
Final Analyses 
Final analysis of the data captured in Part 1 and Part 2 for both Arm A and Arm B will be 
undertaken following 12 months post LSFD. Within each arm, data from the two parts 
may be combined for some analyses at the final analysis, as appropriate. 
Following the final analysis, the study will move into the PACT phase and the clinical 
study database will be closed to new data. Participants who are receiving belantamab 
mafodotin monotherapy or in combination with Len/Dex (Arm A) or Bor/Dex (Arm B) 
may continue to receive belantamab mafodotin monotherapy or in combination with 
either Len/Dex (Arm A) or Bor/Dex (Arm B) if they are gaining clinical benefit as 
assessed by the investigator until they meet any criterion for permanent discontinuation 
of study intervention (see Section 9 and Section 10.2 of GSK Document Number TMF-
14624358). 
The end of study is defined when the last patient had their last visit (last subject last dose 
plus 70 days SAE reporting period). GSK retains the right to request additional 
information for any patient with ongoing AE(s)/SAE(s) ocular data at the end of the 
study. All participants will be monitored and receive follow-up care in accordance with 
standard local clinical practice. 
 


 
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4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
All Screened  
• 
All participants who sign the ICF to participate in the 
clinical trial. 
Screen failure 
summary 
All Treated 
• 
All participants who received at least one dose of study 
treatment.  
Study Population, 
Efficacy, Safety, 
Patient Reported 
Outcomes 
Pharmacokinetic 
(PK) 
• 
Participants in the All Treated population from whom at 
least one PK sample was obtained, analyzed, and was 
measurable. Separate PK populations will be defined for 
each drug (belantamab mafodotin, lenalidomide, and 
bortezomib). Lenalidomide PK population will be split 
between subjects on 25mg and 10mg of lenalidomide. 
PK 
Pharmacodynamic 
(PD) 
• 
Participants in the ‘All Treated’ population for whom a 
biomarker sample was obtained, was analysed and it 
was found measurable. 
Biomarker 
Refer to Appendix 12 which details the population used for each display. 
 
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 [Version 6.0, dated 
14DEC2022].  
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 separate summary and listing of all inclusion/exclusion criteria deviations may also be 
provided. This summary will be based on data as recorded on the inclusion/exclusion 
page of the eCRF. 
 


 
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5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
5.1. 
Study Treatment & Sub-group Display Descriptors 
Data Displays for Reporting [1] 
 
Description [2] 
Data Display [2] 
Order 
in TLF 
Deliverable [3] 
Arm A: GSK2857916 1.9 mg/kg 
STRETCH + Len/Dex 
GSK916 1.9mg/kg STRETCH +Rd 
1 
Interim 2, SAC 
Arm A: GSK2857916 1.9 mg/kg 
SINGLE + Len/Dex 
GSK916 1.9mg/kg SINGLE +Rd 
2 
Interim 2, SAC 
Arm A: GSK2857916 2.5 mg/kg 
SPLIT + Len/Dex 
GSK916 2.5mg/kg SPLIT +Rd 
3 
Interim 2, SAC 
Arm A: GSK2857916 2.5 mg/kg 
SINGLE + Len/Dex 
GSK916 2.5mg/kg SINGLE +Rd 
4 
Interim 2, SAC 
Arm B: GSK2857916 1.9 mg/kg 
STRETCH + Bor/Dex 
GSK916 1.9mg/kg STRETCH +Vd 
1 
Interim 3, SAC 
Arm B: GSK2857916 1.9 mg/kg 
SINGLE + Bor/Dex 
GSK916 1.9mg/kg SINGLE +Vd 
2 
Interim 3, SAC 
Arm B: GSK2857916 2.5 mg/kg 
S/D STRETCH + Bor/Dex 
GSK916 2.5mg/kg S/D STRETCH 
+Vd 
3 
Interim 3, SAC 
Arm B: GSK2857916 2.5 mg/kg 
STRETCH + Bor/Dex 
GSK916 2.5mg/kg STRETCH +Vd 
4 
Interim 3, SAC 
Arm B: GSK2857916 2.5 mg/kg 
SPLIT + Bor/Dex 
GSK916 2.5mg/kg SPLIT +Vd 
5 
Interim 1, Interim 3, 
SAC 
Arm B: GSK2857916 2.5 mg/kg 
SINGLE + Bor/Dex 
GSK916 2.5mg/kg SINGLE +Vd 
6 
Interim 1, Interim 3, 
SAC 
Arm B: GSK2857916 3.4 mg/kg 
SPLIT + Bor/Dex 
GSK916 3.4mg/kg SPLIT +Vd 
7 
Interim 1, Interim 3, 
SAC 
Arm B: GSK2857916 3.4 mg/kg 
SINGLE + Bor/Dex 
GSK916 3.4mg/kg SINGLE +Vd 
8 
Interim 1, Interim 3, 
SAC 
Notes:  
[1] No randomization schedule is planned for this double-arm open label study  
[2] Rd: Lenalidomide Plus Dexamethasone; Vd: Bortezomib Plus Dexamethasone 
[3] SAC = Statistical Analysis Complete (final analysis); Specifics of Interim 1, Interim 2, Interim 3, and SAC 
deliverables are defined in Section 15.12.2. 
 


 
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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 laboratory data, baseline will be the latest non-missing pre-dose value from central 
lab. If no central lab value is available, the latest non-missing pre-dose value from local 
lab will be used. If there are multiple assessments on the same day, the mean will be used 
as the baseline value.  
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing. 
 


 
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5.3. 
Examination of Covariates, Other Strata and Subgroups 
5.3.1. 
Examination of Subgroups 
The list of subgroups may be used in descriptive summaries and statistical analyses. 
Additional subgroups of clinical interest may also be considered. 
• Subgroup analyses will be performed over all doses combined, within each Arm 
(Arms A and B), as well as within the 2.5 mg/kg SINGLE dose alone. 
• If the percentage of participants is small within a particular subgroup, then the 
subgroup categories may be refined. 
Subgroup 
Categories  
Age Group (at screening) 
18 to <65, 65 to < 75, ≥ 75  
Sex 
Male, Female 
Race 
White, Black, Other/Missing 
ISS Staging at Screening 
I vs II/III (do not include unknown stages) 
Number of prior lines of therapy 
1 vs. 2/3 vs. 4+ and 1 vs. >1 
Myeloma Immunoglobulin 
IgG, Non-IgG, Both 
Cytogenetics Risk [1] 
High, Other (non-high risk - all others) 
ECOG Performance Status 
0-1, 2+ 
Prior Bortezomib 
No, Yes 
Prior Daratumumab 
No, Yes 
Prior Lenalidomide 
No, Yes 
NOTES: 
[1] A participant is considered as high risk if the participant has any of the following cytogenetics: t(4;14), 
t(14;16), and 17p13del. 
 
 


 
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5.4. 
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 
Section15.1 Appendix 1: Assessment Windows 
Section15.2 Appendix 2: Study Phases and Treatment Emergent Adverse Events 
Section15.3 Appendix 3: Data Display Standards & Handling Conventions 
Section15.4 Appendix 4: Derived and Transformed Data 
Section15.5 Appendix 5: Reporting Standards for Missing Data 
Section15.6 Appendix 6: 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.  
Study population analyses including analyses of participant’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
anti-cancer therapy, and exposure and treatment compliance will be based on GSK Core 
Data Standards. Details of the planned displays are presented in Appendix 12. 
 
6.2. 
Disposition of Participants 
A summary of subject status and reason for study withdrawal will be provided. This 
display will show the number and percentage of subjects who withdrew from the study, 
including 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 subjects 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.  
To understand the impact of COVID-19, related analyses will include summaries of 
subject status, and subject disposition by relationship to COVID-19 pandemic. An 
additional summary of treatment status and reasons for discontinuation of belantamab 
mafodotin by relationship to COVID-19 pandemic will also be produced, and added to 
existing discontinuation displays. 
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. Age, height, weight, and BMI will 
be summarized using the mean, standard deviation, minimum, median, and maximum. 
The count and percentage will be computed for sex and ethnicity. 
Race and racial combinations may be summarized and listed. 
Disease history and characteristics at screening will be summarized. Disease 
characteristics at screening will include stage, relapsed or refractory disease, 
extramedullary disease, lytic bone lesions, myeloma immunoglobulin, myeloma light 
chain, type of multiple myeloma, lines of therapy completed prior to screening, ECOG 
performance status, genetics, and high-risk cytogenetics. For lines of therapy completed 
prior to screening, groups will be displayed as no lines, 1 line, 2 lines, …, 20 lines, more 
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summarized with n, mean, standard deviation, median, min, and max. For ECOG 
performance status, groups will be displayed as 0, 1, 2, for both Arms A and B. 
Substance use, including smoking history and alcohol use may be summarized. 
Prior anti-cancer therapy will be coded using GSK Drug coding dictionary, then 
summarized by ingredient and listed. 
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 defined in Section 6.5 ‘Extent of Exposure’. 
6.5. 
Extent of Exposure 
Extent of exposure to belantamab mafodotin, lenalidomide, bortezomib, and 
dexamethasone will be summarized. 
The start date of the overall study treatment is defined as the first dose date of belantamab 
mafodotin. 
The overall duration of exposure to study treatment (defined in Section 15.4.2) will be 
calculated and summarized in weeks, using mean, median, standard deviation, minimum, 
and maximum. 
Descriptive statistics of dose intensity will be summarized overall for belantamab 
mafodotin, lenalidomide, bortezomib, and dexamethasone separately. An additional table 
of dose intensity by expected duration of exposure may also be summarized. This “dose 
intensity by expected duration of exposure” summary will adjust for delayed cycles by 
using cumulative dose from the last non-missing visit, and an estimate of expected 
duration of exposure.  
The dose intensity calculation is described below.  
• For Arm A SINGLE/SPLIT belantamab mafodotin doses, as well as lenalidomide 
and dexamethasone: Dose intensity (units/4 weeks) = cumulative actual dose 
divided by duration of exposure in 4 weeks (duration of exposure in days / 28). 
• For Arm A STRETCH belantamab mafodotin doses: Dose intensity (units/8 
weeks) = cumulative actual dose divided by duration of exposure in 8 weeks 
(duration of exposure in days / 56). 
• For Arm B SINGLE/SPLIT belantamab mafodotin doses, as well as bortezomib 
and dexamethasone: Dose intensity (units/3 weeks) = cumulative actual dose 
divided by duration of exposure in 3 weeks (duration of exposure in days / 21).  


 
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• For Arm B STRETCH belantamab mafodotin doses: Dose intensity (units/6 
weeks) = cumulative actual dose divided by duration of exposure in 6 weeks 
(duration of exposure in days / 42).  
 
• Duration of exposure in days used for the dose intensity calculation is defined as: 
end date of the cycle – first dose date + 1 day. The end date of the cycle is defined 
as the cycle start date + 27 days (Arm A SINGLE/SPLIT belantamab mafodotin, 
Len, Dex), or + 55 days (Arm A STRETCH belantamab mafodotin), or + 20 days 
(Arm B SINGLE/SPLIT belantamab mafodotin, Bor, Dex), or + 41 days (Arm B 
STRETCH and S/D STRETCH belantamab mafodotin).  
 
Note: Dose intensity units will depend on treatment being summarized (belantamab 
mafodotin, lenalidomide, bortezomib, dexamethasone). Specifics on treatment units can 
be found in Section 8 of study protocol (Version: GSK Document Number TMF-
14624358). Also, dose intensity for lenalidomide will be split by subjects with a first dose 
of 25mg versus those with a first dose of 10mg.  
Relative dose intensity (RDI) will also be summarized for belantamab mafodotin, 
lenalidomide, bortezomib, and dexamethasone separately. For belantamab mafodotin, 
RDI will be split, with a calculation for Dose 1 and a separate calculation post-Dose 1. 
Relative dose intensity is calculated as a percent and is defined as 100*(mean overall 
dose intensity divided by planned dose intensity). Planned dose intensity for each 
treatment is calculated as:  
 
• Belantamab Mafodotin = planned dose of 1.9 mg/kg, 2.5 mg/kg, or 3.4 mg/kg. 
For the 2.5 S/D STRETCH dose, 2.5 mg/kg will be used for RDI at Dose 1 and 
1.9 mg/kg will be used for RDI post-Dose 1. 
• Lenalidomide = 525 mg for subjects with a first dose of 25mg, and 210 mg for 
subjects with a first dose of 10 mg.  
• Bortezomib = 5.2 mg/m2 
• Dexamethasone = 160 mg for subjects with a first dose of 40mg (Arm A) or 20mg 
(Arm B), and 80mg for subjects with a first dose of 20mg (Arm A) or 10mg (Arm 
B). For Arm B, if a subject’s first dose is ≥20mg, their first dose will be 
considered 20mg for planned dose, and a first dose <20mg will be considered 
10mg for planned dose. 
Summaries of Dose Modifications:  
The summaries of dose modifications will be provided. All the dose reductions, infusion 
interruptions, and dose delays will be summarized or listed. 
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 1-28, 29-56 and 
>56 days for participants in Arm A, and 1-21, 22-42 and >42 days for participants in Arm 
B, will be computed. Primary reasons for dose reductions and dose delays will also be 
summarized by visit.  


 
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Duration of delays is defined as period from the expected start date of dose to actual start 
date of current dose: 
• Calculation for SINGLE dose: (actual start date of current dose - expected start 
date of dose). Expected start date of dose = actual start date of previous dose + 28 
(Arm A), and actual start date of previous dose + 21 (Arm B).  
 
• Calculation for SPLIT dose:  
o Day 1: (actual start date of current dose – (actual start date of previous 
dose + 21) (Arm A), and (actual start date of current dose – (actual start 
date of previous dose + 14) (Arm B). For Arm A the previous dose must 
be a day 8 – 28 and for Arm B the previous dose must be a day 8 – 21. If 
the previous dose is a day 1, then use the same calculation used for 
SINGLE dose.  
 
o Day 8: (actual start date of current dose – (actual start date of previous 
dose + 7) (Arms A and B). For Arms A and B, the previous dose must be a 
day 1 – 7. If the previous dose is not a day 1, then use the same calculation 
used for SINGLE dose. 
 
• Calculation for STRETCH dose: (actual start date of current dose - expected start 
date of dose). Expected start date of dose = actual start date of previous dose + 56 
(Arm A), and actual start date of previous dose + 42 (Arm B).  
 
Duration of Follow-up:  
 
Duration of Follow-Up will be summarized for all participants and is defined as the time 
from first dose to last contact or death. Duration of Follow-up will also be summarized 
for subjects with ongoing follow-up, that is, subjects within the 
 follow-up 
period, with status alive or unknown. 
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 subjects 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 
System) information will be included in the dataset created but will not appear on the 
listing or summary.  
Concomitant medications will be summarized by base ingredient. Each participant is 
counted once within each ingredient . For example, if a participant takes Amoxycillin on 
two separate occasions, the participant is counted only once under the ingredient 
“Amoxycillin”. Note: In order to be considered a concomitant medication, the 
concomitant medication must have been taken at some point during the on-treatment 
study phase. 
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Blood products or blood supportive care products with onset date within the on-treatment 
study phase 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 
7.1. 
Primary Efficacy Analyses 
7.1.1. 
Endpoint/Variables 
BOR 
Best Overall Response (BOR) is defined as the best confirmed response (stringent 
Complete Response [sCR] > Complete Response [CR] > Very Good Partial Response 
[VGPR] > Partial Response [PR] > Minimal Response [MR] > Stable Disease [SD] > 
Progressive Disease [PD] > Not Evaluable [NE]) from treatment start date until disease 
progression or initiation of new anti-cancer therapy, whichever is earlier, as assessed by 
the investigator per IMWG (2016). Details on derivation of confirmed response are 
provided in Table 6. 
 
ORR  
Overall Response Rate (ORR), defined as the percentage of participants with a confirmed 
PR or better (i.e., PR, VGPR, CR, and sCR) as the BOR, per IMWG (2016).  
ORR at final analysis will be analyzed based on the confirmed responses, which will be 
derived based on the algorithm specified in Table 6. ORR at interim analyses should also 
be analyzed based on confirmed responses if available. 
7.1.1.1. 
Derivation of Confirmed Response  
The derivation of confirmed response shall be based on the algorithm specified in Table 
6. The date of the first of the two consecutive assessments will be used as the date of the 
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Table 6 
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 
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 
SD 
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 
No subsequent disease 
assessment: subject has not 
died, discontinued from study 
Unconfirmed 
sCR/CR/VGPR/PR/MR/PD 
 


 
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# 
Response at the First Time 
Point 
Response at Subsequent 
Disease Assessment1 
Confirmed Response at 
the First Time Point 
or bone lesion) 
or (except for PD) started new 
anti-cancer therapy; but as yet 
has no further adequate 
disease assessments 
Will be categorized as NE 
for final ORR analysis. 
 
For ORR analysis in IA, the 
unconfirmed response (PR 
or better) will be counted as 
responder. 
15 
SD 
Any 
 
OR 
No subsequent disease 
assessment 
SD 
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 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. 
 
Note:  
• 
SD does not need to be confirmed. 
• 
PD due to imaging (i.e., plasmacytoma or bone lesion) does not need to be confirmed. 
• 
Where criteria are not mutually exclusive, take the first that applies. 
• 
As per IMWG criteria (Kumar, 2016), “If patients do not have measurable disease at baseline, they can only be 
assessed for at least a complete response or progressive disease.” 


 
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7.1.2. 
Summary Measure 
ORR 
The number and percentage of participants with the BOR in the following response 
categories will be summarized at interim and final analysis for each treatment arm: sCR, 
CR, VGPR, PR, overall response (sCR+CR+VGPR+PR), minimal response (MR), stable 
disease (SD), progressive disease (PD), and not evaluable (NE). The corresponding exact 
95% CI for ORR will also be provided. Participants with unknown or missing responses 
will be treated as non-responders, i.e., these participants will be included in the 
denominator when calculating percentages of response. 
 
For subgroup analysis, ORR will be presented using forest plot for categories defined in 
Section 5.3.1. 
7.1.3. 
Population of Interest 
The primary efficacy analyses will be based on the All Treated population for all 
analyses, unless otherwise specified. 
7.1.4. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 12 and will be based on GSK 
data standards and statistical principles. 
Unless otherwise specified, endpoints / variables defined in Section 2.2 will be 
summarized using descriptive statistics, graphically presented (where appropriate) and 
listed. 
 
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8. 
SAFETY ANALYSES 
The safety analyses will be based on the All Treated population, unless otherwise 
specified.  
8.1. 
Adverse Events Analyses 
Adverse events (AEs), Serious AEs (SAEs) and other significant AEs will be analyzed 
based on GSK Core Data Standards. AE displays showing information by preferred term 
and max grade will use treatment emergent AEs. All other AE displays will use on-
treatment AEs. Details for treatment-emergent and on-treatment AEs are provided in 
Section 15.2.3. Dose-limiting toxicity (DLT) will also be summarized according to GSK 
Oncology Data Standards. The details of the planned displays are provided in Appendix 
12. 
Adverse events will be graded by the investigator according to the National Cancer 
Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE),Version 4.03 
[NCI, 2010]. Adverse events will be coded using the Medical Dictionary for Regulatory 
Affairs (MedDRA dictionary) and grouped by system organ class (SOC). In addition, 
corneal findings will also be graded using the GSK scale for corneal events provided in 
Table 9. 
An overview summary of AEs, including counts and percentages of subjects with any 
AE, AEs related to GSK2857916/study treatment, Grade 3&4 AEs, Grade 3&4 AEs 
related to GSK2857916/study treatment, AEs leading to permanent discontinuation of 
study treatment, AEs related to GSK2857916/study treatment and leading to permanent 
discontinuation of study treatment, AE leading to dose reductions, AEs leading to dose 
interruption/delay, AEs leading to Infusion stopped early and no completed, SAEs, SAEs 
related to GSK2857916/study treatment, fatal SAEs, and fatal SAEs related to 
GSK2857916/study treatment will be produced. 
A summary of non-serious AEs that occurred in 5% of the subjects or above will be 
provided (no rounding for the percentage will be used in terms of 5% threshold, e.g., 
event with 4.9% incidence rate should not be included in this table). SOC and PT. will 
display the summary 
The relationship between MedDRA PT, and Verbatim Text will be displayed. 
A summary of number and percentage of subjects with any AEs by maximum grade will 
be produced. Adverse events will be sorted by Preferred term (PT) in descending order of 
total incidence. The summary will use the following algorithms for counting the subject: 
• Preferred term row: Participants experiencing the same AE preferred term 
several times with different grades will only be counted once with the maximum 
grade. 
• 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. 


 
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In addition, the frequency and percentage of AEs (all grades) will be summarized and 
displayed in three ways: 1) in descending order of total incidence by PT only, 2) in 
descending order of total incidence by System Organ Classes (SOC) and PT, and 3) in 
descending order of total incidence by System Organ Classes (SOC) and PT and 
Maximum Grade. In the SOC row, the number of subjects with multiple events under the 
same system organ class will be counted once.  
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 in descending order 
of total incidence by PT and Maximum Grade. 
A summary of the number of patients experiencing DLTs will be provided.  
To understand the impact of COVID-19, the following displays will be provided:  
• Number of subjects with suspected, probable, or confirmed for COVID-19 
infection 
Details on how to define when COVID-19 pandemic measures began are provided in 
Section 15.10. 
 


 
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8.2. 
Adverse Events of Special Interest Analyses 
8.2.1. 
Belantamab Mafodotin 
Characteristics (e.g., number of occurrences, action taken, maximum grade, etc.) of the 
following AEs of special interest related to belantamab mafodotin will be summarized 
separately:  
• Corneal events, Keratopathy events 
• Thrombocytopenia 
• Infusion related reactions 
For thrombocytopenia and infusion-related reactions (IRR), in addition to events 
identified and collected in eCRF, a comprehensive list of MedDRA terms based on 
clinical review will be used to identify each type of event. Other AESI will be identified 
based on list of terms of interests which will be produced in Integrated Coding Dictionary 
System by Clinical Dictionary Development & Management and provided to Statistics 
and Programming. Changes to the MedDRA dictionary may occur between the start of 
the study and the time of reporting and/or emerging data from on-going studies may 
highlight additional adverse events of special interest, therefore the list of terms to be 
used for each event of interest and the specific events of interest will be based on the 
safety review team (SRT) agreements in place at the time of reporting. The details of the 
planned displays are provided in Appendix 12. 
For infusion related reactions, events would only be considered IRR if the event was 
reported on an infusion day after the start of infusion or within 24 hours following end of 
infusion, and led to a temporary interruption or prolongation of infusion time or treatment 
withdrawal. 
The severity of all AESI will be graded utilizing the National Cancer Institute Common 
Toxicity Criteria for Adverse Events (NCI-CTCAE) v.4.03 [NCI, 2010]. Severity of 
belantamab mafodotin treatment related corneal events will also be graded using the GSK 
scale for corneal events provided in Table 9 and should be used for evaluation of DLT. 
Additional guidance on grading visual acuity changes is provided in Section 15.3.5. 
 


 
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Table 9 
Grading Scalea for Corneal Events Associated with Belantamab 
Mafodotin 
Measure 
 
Grade 1 per GSK 
Scale  
Grade 2 per GSK Scale Grade 3 per GSK Scale Grade 4 per GSK 
Scale 
Ophthalmic 
exam findings 
Mild superficial 
keratopathy 
(change from 
baseline) 
 
Moderate punctate 
keratopathy 
and/or 
Mild/patchy microcysts 
and/or 
Mild/patchy Epithelial or 
stromal edema 
and/or 
Sub-epithelial haze 
(peripheral)  
and/or 
Active stromal opacity 
(peripheral) 
Severe punctate 
keratopathy 
and/or 
Diffuse microcysts 
and/or 
Diffuse Epithelial or 
stromal edema 
and/or 
Sub-epithelial haze 
(central)  
and/or 
Active stromal opacity 
(central) 
Corneal ulcer 
Visual Acuity 
b, c 
Change of 1 line 
from baseline 
Change of 2-3 lines from 
baseline and not worse 
than 20/200b 
Change of more than 3 
lines from baseline and not 
worse than 20/200b 
 
Worse than Vision 
20/200b 
Note: Standardized guidance for grading ophthalmic findings associated with GSK2857916 is provided to 
sites in the eCRF and ophthalmology SRM information. Ophthalmic exam findings as described must be 
present in a participant to utilize the GSK grading scale.  
a. 
Grading is based on most severe finding. If eyes differ in severity, GSK grading scale should be based 
on the more severe eye.  
b. 
Change in visual acuity should be due to corneal events associated with GSK2857916. If change in 
vision is for reason other than corneal events, ophthalmic exam findings will drive event grading.  
c. 
See Section 15.3.5 for additional guidance on how to grade changes in visual acuity depending on 
baseline vision. If a participant has a baseline visual acuity of 20/200 or worse in an eye, ophthalmic 
exam findings will drive event grading 
 
Summaries of the number and percentage of subjects 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 for some events will be summarized using 
summary statistics mean, standard deviation, median, minimum value, and maximum. 
The number and percentage of subjects who have time of onset of first occurrence (1-28, 
29-56, 57-84, >84 days for Arm A, and 1-21, 22-42, 43-63, >63 days for Arm B) will be 
reported. The number and percentage of subjects who have duration of first occurrence 
(1-28, 29-56, >56 days for Arm A, 1-21, 22-42, >42 days for Arm B) will be reported. 
The summary of event characteristics will also be provided, including number of subjects 
with event, number of events, event characteristics (serious, study treatment related), 
number of events per subject (one, two, three or more), worst outcome 
(recovered/resolved, recovered/resolved with sequelae, recovering/resolving, not 
recovered/not resolved, fatal), and maximum grade. The percentage will be calculated in 
two ways, one with number of subjects with event as the denominator and the other with 
total number of subjects as the denominator, within each cohort and treatment group. The 
worst-case approach will be applied at subject level for the maximum grade, i.e., a 
subject will only be counted once as the worst case from all the events experienced by the 
subject. For action taken to an event, subject will be counted once under each action, e.g., 


 
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if a subject has an event leading to both study treatment discontinuation and dose 
reduction, the subject will be counted once under both actions. 
8.2.1.1. 
Other Risks 
Characteristics (e.g., number of occurrences, action taken, maximum grade, etc.) of the 
important other risk, neutropenia, will be summarized separately. The severity of 
neutropenia will be graded utilizing the NCI-CTCAE v.4.03 [NCI, 2010]. 
A comprehensive list of MedDRA preferred terms for neutropenia based on clinical 
review will be used to identify each type of event. Neutropenia will be identified based 
on list of terms of interests which will be produced in Integrated Coding Dictionary 
System by Clinical Dictionary Development & Management and provided to Statistics 
and Programming. Changes to the MedDRA dictionary may occur between the start of 
the study and the time of reporting and/or emerging data from on-going studies may 
highlight additional risks; therefore, the list of terms to be used for each event and the 
specific events will be based on the safety review team (SRT) agreements in place at the 
time of reporting. The details of the planned displays are provided in Appendix 12. 
Summaries of the number and percentage of subjects with these events will be provided 
for each type of events separately by preferred term and maximum grade.  
The summary of event characteristics will also be provided and will be calculated 
similarly as the AESI for belantamab mafodotin as provided in Section 8.2. 
8.2.2. 
Corneal events (GSK scale) 
Following discussions with regulatory agencies, GSK developed a grading scale to 
capture both corneal examination findings and visual acuity changes in participants 
treated with belantamab mafodotin. This GSK scale differs from the CTCAE criteria for 
eye disorders which relies mainly on patient’s symptoms and patient’s ability to attend to 
‘activities of daily living’ for grading of events. Details of derivation of this GSK scale 
based on corneal findings and visual acuity Ophthalmic Exam (collected from Ocular 
form) can be found in Table 33 and Table 34 of study protocol (Version: GSK Document 
Number TMF-14624358). 
In addition to the listing, the following outputs will be provided for corneal events graded 
using the GSK scale:  
1. Overview for corneal event (GSK scale)  
2. Summary of Grade of GSK scale 
a. Summary of Characteristics of Corneal Events (GSK scale) including 
the percentage of duration of exposure (see Section 15.4.2 for 
definition) that is having corneal events (GSK scale) with grade ≥ 2 
and grade ≥ 3 respectively  


 
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b. Summary of onset time and duration of the first occurrence of corneal 
event (GSK scale) of grade 2 or above 
3. Summary of actions taken with study treatment (e.g., dose 
reduction/delay/study treatment withdrawn) 
4. Summary of worst post-baseline corneal events (GSK scale) 
 
5. Summary of Best Corrected Visual Acuity Test (BCVA) Scores (logMAR 
score) due to Corneal Event (GSK Scale) 
 
Exposure-adjusted incidence rates for grade 3+ corneal events (GSK Scale) will be 
summarized. Exposure-adjusted rates (rate/100 PY) are defined as the number of 
participants with an occurrence of a grade 3+ corneal event (first occurrence in worse 
eye, max grade, GSK Scale), divided by the total exposure duration in years across all 
participants at risk within a dose group, multiplied by 100. Exposure duration in years for 
each participant is calculated as:  
• For participants who do not experience a grade 3+ corneal event: (Duration of 
Exposure (as defined in Section 6.5)) / 365.25 
 
• For participants that do experience a grade 3+ corneal event: (Date of first max 
grade 3+ corneal event in worse eye (GSK Scale) – first dose date + 1) / 365.25 
For recurring grade 3+ events, the first occurrence of the event will be reported.  
Details of the planned displays are provided in Appendix 12. 
 
8.2.3. 
Eye Disorder (CTCAE) 
A summary of characteristics of blurred vision events (CTCAE) will be provided, 
including number of subjects with an event, total number of events, event characteristics 
(serious, related to GSK2857916, related to any study treatment), number of events per 
subject, worst outcome, maximum grade, and action taken.  
8.3. 
Deaths and Serious Adverse Events 
All deaths will be summarised based on the number and percentage of participants. This 
summary will classify participants by time of death relative to the last dose of treatment 
(>30 days or ≤30 days) and primary cause of death (disease under study, SAE possibly 
related to study treatment, or other).  
All SAEs will be tabulated based on the number and percentage of subjects 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. The 
summary of all SAEs will also be created by SOC and PT. In addition, a summary of 
cumulative incidence of SAE by number of doses received at first occurrence will be 
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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.  
SAEs are included in the listing of all adverse events. Separate supportive listings with 
participant-level details will be generated for 
• Fatal SAEs  
8.4. 
Adverse Events Leading to Discontinuation and Dose 
Modification 
The following categories of AEs will be summarized separately in descending order of 
total incidence 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 
Additionally, dose modifications will be assessed separately for all AEs, corneal AEs, 
and non-corneal AEs. 
8.5. 
Ocular findings from ophthalmic exam  
As outlined in study protocol (Version: GSK Document Number TMF-14624358) 
Schedule of Activities, ophthalmic exams are scheduled at screening, during the study, 
and follow-up period for subjects in study. The ocular findings from ophthalmic exams 
will be analysed as described below. 
1. Ocular findings for General study (Baseline to Last follow-up): 
a. Summary of Best Corrected Visual Acuity Test (BCVA) Scores (logMAR 
score), and Summary of Best Corrected Visual Acuity Test (BCVA) 
Scores (logMAR score) due to Corneal Event (GSK Scale) – includes 
summaries of BCVA (logMAR score) at baseline, EOT visit, and last 
follow-up visit as well as worst and most frequent category (definite 
worsen, possible worsen, and no change/improved) of change from 
baseline summarized by eye (R/L) and subject (better eye). Changes of 
logMAR score from baseline to end of treatment visit, last follow-up exam 
and maximum (worst) change from baseline will be summarized based on 
the following categories: no change/improved vision: a change from 
baseline <0.12; a possible worsened vision: a change from baseline 
>=0.12 to <0.3; a definite worsened vision: a change from baseline >=0.3. 
 
b. Number (%) of Subjects with a Decline in Best Corrected Visual acuity 
(BCVA) to LP or NLP due to a Corneal Event Anytime Post-Baseline  


 
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c. Summary of Worst Post-Baseline Best Corrected Visual Acuity (BCVA) 
Change in Snellen Results 
d. Shift in Corneal Epithelium Findings from Baseline to Worst Post-
Baseline  
 
e. Summary of Findings for Punctate Keratopathy 
 
The details of the planned displays are provided in Appendix 12. 
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 
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. Summary 
of change from baseline by scheduled visits using mean, median, standard deviation, 
minimum and maximum will be provided. 
Summaries of worst-case grade increase from baseline grade will be provided for all the 
lab tests that are gradable by CTCAE v4.03. These summaries will display the number 
and percentage of subjects 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. 
For lab tests that are not gradable by CTCAE v4.03, summaries of worst-case changes 
from baseline with respect to normal range will be generated. Decreases to low, changes 
to normal or no changes from baseline, and increases to high will be summarized for the 
worst-case post-baseline. If a participant has a decrease to low and an increase to high 
during the same time interval, then the participant is counted in both the “Decrease to 
Low” categories and the “Increase to High” categories.  
Separate summary tables for haematology, and chemistry laboratory tests will be 
produced. Liver function laboratory tests will be included with chemical chemistry. 
Detailed derivation of baseline assessment is specified in Section 5.2. Unless otherwise 
specified, the denominator in percentage calculation at each scheduled visit will be based 
on the number of subjects with non-missing value. 


 
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Unless otherwise specified, the denominator in percentage calculation at each scheduled 
visit will be based on the number of subjects with non-missing value. 
8.8. 
Other Safety Analyses 
8.8.1. 
ECG 
The analyses of non-laboratory safety test results including ECGs will be based on GSK 
Core Data Standards, unless otherwise specified. The details of the planned displays are 
presented in Appendix 12. 
A summary of the number and percentage of subjects who had normal and abnormal 
(clinically significant and not clinically significant) ECG findings will be displayed by 
scheduled visits as well as for the worst-case post-baseline. 
 
The QTc values based on Fridericia formula will be rounded to the integer and the values 
will be categorized into the following ranges: Grade 0 (<450), Grade 1 (450-480), Grade 
2 (481-500), and Grade 3 (≥501). Summaries of grade increase will be provided for some 
analyses. These summaries will display the number and percentage of subjects with any 
grade increase.  
The changes in QTc values will be categorized into the clinical concern ranges which are 
specific to changes in QTc: 31-60, and >60 msec, and >530msec. A summary of change 
in QTc value will display the number and percentage of subjects with a change within 
each range in the worst-case post-baseline only. Subjects with missing baseline values 
will be excluded from this summary. 
The summaries of QTc will use the collected values based on Fridericia formula. 
8.8.2. 
Anti-Drug Antibody Analyses 
For each subject, the anti-GSK2857916 (drug) antibody results, titers, and neutralizing 
antibody assay results, and also ADC and total antibody concentration will be listed for 
each assessment time point. The frequency and percentage of subjects with positive and 
negative anti-drug antibody and neutralizing antibody assay results will be summarized 
for each assessment time and overall, for each subject by dose cohort. The conclusive 
results will be based on the total antibody concentration. 
8.8.3. 
Profile Plot 
A profile plot for subjects within both Arms A and B will be produced. This plot will 
display Study Treatment Duration (Days) for each subject, along with an indication of 
each subject’s actual dose over time, investigator assessed confirmed response, 
highlighting responders versus non-responders, and those ongoing on belantamab 
mafodotin study treatment (ongoing indicator at interims only).  


 
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9. 
PHARMACOKINETIC ANALYSES 
Concentration-time data collected will be analyzed using standard non-compartmental 
methods; some parameters will be determined for all participants and cycles. The 
concentration-time data may be combined with data from other studies and will be 
analyzed in a population approach using nonlinear mixed effects modeling and may be 
provided in a separate report. 
For all mean and median measures within tables or figures, means/medians will only be 
calculated if the number of evaluable samples is greater than or equal to 3. Similarly, 
standard deviation and coefficient of variation measures will only be calculated for 
samples greater than or equal to 3.  
9.1. 
Drug Concentration Measures  
Plasma concentrations of belantamab mafodotin, total mAb, and cys-mcMMAF will be 
summarized using descriptive statistics, graphically presented (where appropriate) and 
listed by treatment arm and dose group. All dose groups will be on each figure as 
appropriate (Refer to Appendix 3 (Section 15.3)). 
Linear and semi-logarithmic individual concentration-time profiles and mean and median 
profiles (when appropriate) will be plotted for lenalidomide and bortezomib. 
Concentrations of bortezomib and lenalidomide will be listed for each participant and 
summarized (when appropriate) by planned time point. 
9.2. 
Derived Pharmacokinetic Parameters  
9.2.1. 
Belantamab Mafodotin, Total mAb, and Cys-mcMMAF 
Pharmacokinetic analyses of derived pharmacokinetic parameter values of belantamab 
mafodotin, total mAb, and/or cys-mcMMAF will be conducted based on the 
Pharmacokinetic (PK) Analysis Set, as data permit. 
• The following pharmacokinetic parameters described in the table below will be 
determined separately for each analyte and dosing regimen, as data permit and as 
outlined in Table 10 
 
 
 
 
 
 
 


 
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Table 10 
Derived Pharmacokinetic Parameters from NCA or Population PK 
analyses 
Parameter 
Parameter Description 
AUC(0-x) 
Area under the concentration-time curve from time zero to time x (i.e., 168, 504, 
672, 1008 hours) 
AUC(0-) 
Area under the concentration-time curve during the dosing interval 
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 
C, Ctrough 
Trough concentration prior to the next dose for each cycle 
C-EOI 
Observed plasma concentration at the end of infusion 
tlast 
Time of last observed quantifiable concentration  
NOTES: Additional parameters may be included as required. 
 
Derived PK Parameters for Analytes and Dose Regimen for Arm A 
Analyte 
(Unit) 
Dosing Regimen 
Single 
Split 
Stretch 
 Belantamab 
mafodotin 
(µg/mL) 
AND 
Total mAb 
(µg/mL) 
Cmax (C1D1)  
Tmax (C1D1)  
Tlast (C1D1)  
AUC0-504h (C1D1) 
AUC0-672h (C1D1)   
 
Cmax (C1D1)  
Tmax (C1D1) 
Tlast (C1D1) 
AUC0-504h (C1D1) 
AUC0-672h (C1D1)   
Cmax (C1D8) 
Tmax (C1D8) 
Cmax (C1D1)  
Tmax (C1D1)  
Tlast (C1D1)   
AUC0-504h  
AUC0-672h (C1D1)   
AUC0-1008h (C1D1)  
AUC0-1344 (C1D1)  
cys-mcMMAF 
(ng/mL) 
Cmax (C1D1)  
Tmax (C1D1)   
Tlast (C1D1)  
AUC0-168h  (C1D1) 
Cmax (C1D1)  
Tmax (C1D1)  
AUC0-168h (C1D1) 
AUC0-336h (C1D1) 
Tlast (C1D1) 
Cmax (C1D8)  
Tmax (C1D8) 
AUC0-168h (C1D8)  
Cmax (C1D1)  
Tmax (C1D1)   
Tlast (C1D1)  
AUC0-168h (C1D1) 
C1D1 is Cycle 1 Day 1 
C1D8 is Cycle 1 Day 8 
 
Derived PK Parameters for Analytes and Dose Regimen for Arm B 
Analyte 
(Unit) 
Dosing Regimen 
Single 
Split 
Stretch and S/D 
Stretch 
 Belantamab 
mafodotin 
(µg/mL) 
AND 
Total mAb 
(µg/mL) 
Cmax (C1D1)  
Tmax (C1D1)  
Tlast (C1D1)  
AUC0-504h (C1D1) 
 
Cmax (C1D1)  
Tmax (C1D1) 
Tlast (C1D1) 
AUC0-504h (C1D1) 
Cmax (C1D8) 
Tmax (C1D8) 
Cmax (C1D1)  
Tmax (C1D1)  
Tlast (C1D1)   
AUC0-504h (C1D1)  
AUC0-1008h (C1D1) 
cys-mcMMAF 
Cmax (C1D1)  
Tmax (C1D1)   
Cmax (C1D1)  
Tmax (C1D1)  
Cmax (C1D1)  
Tmax (C1D1)   


 
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(ng/mL) 
Tlast (C1D1)  
AUC0-168h  (C1D1) 
AUC0-168h (C1D1) 
AUC0-336h (C1D1) 
Tlast (C1D1) 
Cmax (C1D8)  
Tmax (C1D8) 
AUC0-168h (C1D8)  
Tlast (C1D1)  
AUC0-168h (C1D1) 
C1D1 is Cycle 1 Day 1 
C1D8 is Cycle 1 Day 8 
 
• The pharmacokinetic parameters 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, or by population pharmacokinetic analysis 
(Section 11) 
• The pharmacokinetic parameters C-EOI and Ctrough will be determined directly 
from the concentration-time dataset. Note: For the dosing occasions with only 
predose and end of infusion samples, the end of infusion sample will not be 
identified as Cmax. Ctrough will not be reported for cys-mcMMAF. 
• All calculations of pharmacokinetic parameters will be based on actual sampling 
times. 
 
9.2.2. 
Lenalidomide and Bortezomib 
Lenalidomide pharmacokinetics in the presence of belantamab mafodotin may be 
analyzed using standard non-compartmental methods, data permitting, according to the 
same methodology as described above, or analyzed using a published population 
pharmacokinetic model. Results of the population PK analysis may be provided in a 
separate report. 
Lenalidomide PK parameters for Arm A 
Analyte 
(Unit) 
Dosing Regimen 
Single 
Split 
Stretch 
Bortezomib 
(ng/mL) 
Cmax 
Tmax 
Tlast 
AUC0-4 
AUC0-24 
 
Cmax 
Tmax 
Tlast 
AUC0-4 
AUC0-24 
Cmax 
Tmax 
Tlast 
AUC0-4 
AUC0-24 
 
Bortezomib pharmacokinetics (see table below) in the presence of belantamab mafodotin 
will be analyzed using standard non-compartmental methods, data permitting, according 
to the same methodology as described above. 
 
 
  


 
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Bortezomib PK parameters for Arm A 
Analyte 
(Unit) 
Dosing Regimen 
Single 
Split 
Stretch 
S/D Stretch 
Bortezomib 
(ng/mL) 
Cmax  
Tmax 
Tlast  
AUC0-last 
AUC0-72h 
 
Cmax  
Tmax 
Tlast  
AUC0-last 
AUC0-72h 
Cmax  
Tmax 
Tlast  
AUC0-last 
AUC0-72h 
 
Cmax  
Tmax 
Tlast  
AUC0-last 
AUC0-72h 
 
AUC0-last will be reported in the listings not in summary tables 
 
9.3. 
Summary Measure 
Parameters listed in Section 9.2 will be summarized. 
9.4. 
Population of Interest 
The pharmacokinetic analyses will be based on the Pharmacokinetic population, unless 
otherwise specified. 
9.5. 
Statistical Analyses / Methods 
Pharmacokinetic parameters will be listed and summarized descriptively (mean, standard 
deviation, median, minimum, maximum, geometric mean, and the standard deviation, 
CV%, and 95% CI of log-transformed parameters) by analyte, arm, dose group, and visit.  
Details of the planned displays are provided in Appendix 12, based on GSK Standards 
and statistical principles. 
 


 
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10. 
PHARMACOKINETIC AND PHARMACODYNAMIC 
ANALYSES 
10.1. 
Exposure-Response for Efficacy and Safety Endpoints 
If deemed appropriate and if data permit, exposure-response relationships between 
belantamab mafodotin exposure (e.g., concentration, Cmax, or AUC) and clinical activity 
and/or toxicity (e.g., response, AESIs) may be explored using population methods. If data 
permit, the effects of covariates may be explored. Time to event endpoints will be 
analyzed using Kaplan-Meier plots and Cox proportional hazard models while probability 
of occurrence of event of interest will be evaluated using logistic regression.  
These analyses will be performed using R (The R Foundation for Statistical Computing), 
NONMEM (ICON Solutions) with PsN (Perl Speaks NONMEM) or another software 
platform deemed appropriate. The analysis will be performed by, or under the direct 
auspices of, Clinical Pharmacology Modelling and Simulation (CPMS), 
GlaxoSmithKline using the currently supported versions of all software packages. 
Results of this analysis may be provided in a separate report. 
 
11. 
POPULATION PHARMACOKINETIC (POPPK) ANALYSIS 
Plasma belantamab mafodotin, and/or cys-mcMMAF concentration-time data may be 
combined with data from other studies and analysed using a population pharmacokinetic 
approach. The objective of this analysis would be to derive individual pharmacokinetic 
parameter values. 
Based on the individual post hoc parameters, derived pharmacokinetic parameter values 
(e.g., CL, Vss, t½, AUC(0-)) will be generated on certain dosing occasions, data 
permitting (see Table 10). These values will be listed and summarized as described in 
Section 9.5. 
The lenalidomide concentration-time data may also be analyzed following the above 
methodology, using a published population PK model for lenalidomide (Guglieri-Lopez, 
2017). 
Further details are provided in Section 15.8. The results of these analyses may be 
provided in a separate report. 
 
 
 


 
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13. 
PATIENT REPORTED OUTCOMES ANALYSES 
All questionnaires will be collected electronically as Electronic Patient Reported 
Outcomes (ePRO). The EORTC QLQ-C30 (version 3.0), EORTC QLQ-MY20, and the 
PRO-CTCAE are three oncology-specific Health-Related Quality-of-Life (HRQoL) 
assessments that will be analysed in this study.  
In addition, the impact of potential corneal event on function and health-related quality-
of-life will be assessed with the use of two visual function questionnaires, the NEI-VFQ-
25, and Ocular Surface Disease Index (OSDI). 
The analyses for EORTC QLQ-C30, EORTC QLQ-MY20, PRO-CTCAE, NEI-VFQ-25, 
and OSDI will be based on the All Treated population, unless otherwise specified. 
13.1. 
Compliance of PRO-CTCAE, OSDI, and EORTC QLQ-C30 
A table to summarize the compliance of PRO-CTCAE, OSDI, and NEI-VFQ-25 and 
EORTC QLQ-C30 and EORTC-QLQ-MY20 by visit will be provided. The tables will 
include number of subjects remaining in study, number, and percentage of subjects with 
PRO-CTCAE score (based on first item), OSDI total score, NEI-VFQ-25 overall 
composite score, QLQ-C30 summary score, and QLQ-MY20 summary score. The 
percentage is calculated using number of subjects remaining in the study at given 
timepoint as denominator. 
The frequency and proportion of missing data for each measure will be evaluated at each 
timepoint. 
13.2. 
Patient Reported Outcome Version of the Common Term 
Criteria for Adverse Events (PRO-CTCAE) 
The PRO-CTCAE is a patient-reported outcome measure developed to evaluate 
symptomatic toxicity in subjects on cancer clinical trials [Basch, 2014]. The PRO-
CTCAE was designed to be used as a companion to the CTCAE, the standard lexicon for 
adverse event reporting in cancer trials. The PRO-CTCAE includes an item library of 
124 items representing 78 symptomatic toxicities drawn from the CTCAE. PRO-CTCAE 
provides a systematic yet flexible tool for descriptive reporting of symptomatic treatment 
side effects in cancer clinical trials. In the present study, a subset of items selected from 
the PRO-CTCAE Version 1.0 Item library will be administered. The levels and related 
code values for PRO-CTCAE are shown below. 
 
 


 
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Levels and related code values 
Response scale 
0 
1 
2 
3 
4 
Frequency 
Never 
Rarely 
Occasionally 
Frequently 
Almost 
Constantly 
Severity 
None 
Mild 
Moderate 
Severe 
Very severe 
Interference 
Not at all 
A little bit 
Somewhat 
Quite a bit 
Very much 
Present/Absence No 
Yes 
 
 
 
 
For each selected item from the library: proportion of PRO-CTCAE scores for attributes 
(frequency, severity and/or interference) will be presented with stacked bar charts by 
visit. Maximum PRO-CTCAE score at post-baseline for each item attribute will be 
summarized by counts and proportions. Proportion of patients with a maximum score of 3 
or 4 for each item attribute (severe or very severe, frequently or almost constantly, quite a 
bit or very much) will also be reported. Proportions will be based on the number of  
patients with available data and subject with missing response will be excluded from 
analysis.  
13.3. 
Visual Function Questionnaires 
13.3.1. 
National Eye Institute Function Questionnaire-25 (NEI-VFQ-25) 
The NEI-VFQ-25 consists of a base set of 25 vision-targeted questions representing 11 
vision-related constructs, plus an additional single-item general health rating question 
[Mangione, 2001]. The NEI-VFQ-25 generates the following vision-targeted sub-scales: 
global vision rating, difficulty with near vision activities; difficulty with distance vision 
activities; limitations in social functioning due to vision; role limitations due to vision; 
dependency on others due to vision; mental health symptoms due to vision; driving 
difficulties; limitations with peripheral vision, limitations with color vision; and ocular 
pain. Details of deriving domain scores and overall composite score can be found in 
Section 15.9.3. 
For overall composite score and each of 11 sub-scale scores, the descriptive summary of 
the actual value and change from baseline by visit will be provided. 
13.3.2. 
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. 
For the OSDI, the total score will be calculated as well as scores for the three subscales 
(ocular symptom: item 1-3; visual related function: item 4-9; and environmental triggers: 
item 10-12).  


 
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The total OSDI score = ([sum of scores for all questions answered × 100]/[total number 
of questions answered ×4]). Subscale scores are computed similarly with only the 
questions from each subscale used to generate its own score. A score of 100 corresponds 
to complete disability (a response of “all of the time” to all questions answered), while a 
score of 0 corresponds to no disability (a response of “none of the time” to all questions 
answered). Therefore, decrease in score from baseline means improvement.  
For total score and each of the three sub-scales, the descriptive summary of the actual  
value and change from baseline at selected time points will be provided. For the Vision-
Related Functioning domain, the number and percentage of participants with post-
baseline score worsening of ≥ 12.5 from baseline score will be summarized.  
Plots of change from baseline (including baseline) and 95% confidence interval over time 
by visit, and at end of study treatment, last follow-up, and worst case post-baseline for 
total score will also be provided. 
13.4. 
Value Evidence and Outcome 
13.4.1. 
European Organization for Research and Treatment of Cancer 
Quality of Life Questionnaire 30-item Core module (EORTC QLQ-
C30) 
The EORTC QLQ-C30 is a 30-item questionnaire containing both single- and multi-item 
measures [Aaronson, 1993]. These include five functional scales (Physical, Role, 
Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and 
Nausea/Vomiting), a Global Health Status/QoL scale, and six single items (Constipation, 
Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). Scores for each 
scale and single-item measure are averaged and transformed linearly to a score ranging 
from 0–100. Details of deriving domain scores (9 scales and 6 single items) and summary 
score can be found in Section 15.9.1. 
• A high score for functional scales and for Global Health Status/QoL represent 
better functioning ability or Health-Related Qualify of Life (HRQoL), (higher 
score indicates improvement) 
• whereas a high score for symptom scales and single items represents significant 
symptomatology [Proskorovsky, 2014]. (Lower score indicates improvement) 
Descriptive summaries (mean, SD, median, min and max) of the actual value and change 
from baseline will be provided for EORTC QLQ-C30 domain scores. The number and 
percentage of participants with post-baseline score improved by ≥ 10 points, respectively 
from baseline score will be summarized. The number and percentage will be provided for 
each domain score. 
Plots of change from baseline (including baseline) and 95% confidence interval over time 
by visit, and at end of study treatment, and worst case post-baseline for individual 
domains will also be provided. 
 


 
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13.4.2. 
European Organization for Research and Treatment of Cancer 
Quality of Life Questionnaire 20-item Multiple Myeloma module 
(EORTC QLQ-MY20) 
The EORTC QLQ-MY20 is a supplement to the QLQ-C30 instrument used in patients 
with multiple myeloma [Aaronson, 1993; Cocks, 2007]. The module comprises 20 
questions that address four myeloma specific HRQoL domains: Disease Symptoms, Side 
Effects of Treatment, Future Perspective, and Body Image. Three of the four QLQ-MY20 
domains are multi-item scales: Disease Symptoms (includes bone aches or pain, back 
pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity); Side 
Effects of Treatment (includes drowsiness, thirst, feeling ill, dry mouth, hair loss, upset 
by hair loss, tingling hands or feet, restlessness/agitation, acid indigestion/heartburn, and 
burning or sore eyes); and Future Perspective (includes worry about death and health in 
the future, and thinking about illness).  The Body Image scale is a single-item scale that 
addresses physical attractiveness. Details of deriving domain scores can be found in 
Section 15.9.2. 
For each of four domain scores, the following summaries will be provided: 
• The descriptive summary of the actual value and change from baseline by visit 
Summary of the number (%) of patients with improvement in score ≥ 10 points by visit. 
Plots of change from baseline (including baseline) and 95% confidence interval over time 
by visit, and at end of study treatment, and worst case post-baseline for disease domain 
will also be provided. 
 
 


 
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14. 
REFERENCES 
Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The 
European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life 
instrument for use in international clinical trials in oncology. J Natl Cancer Institute. 
1993 Mar 3;85(5):365-76. 
Basch E, Reeve BB, Mitchell SA, Clauser SB, Minasian LM, Dueck AC, et al. 
Development of the National Cancer Institute's patient-reported outcomes version of the 
common terminology criteria for adverse events (PRO-CTCAE). J Natl Cancer Inst. 
2014;106(9). 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. 
Biometrics. 1982 Mar 1:29-41.  
Cocks K, Cohen D, Wisløff F, Sezer O, Lee S, Hippe E, et al. An international field study 
of the reliability and validity of a disease-specific questionnaire module (the QLQMY20) 
in assessing the quality of life of patients with multiple myeloma. European Journal of 
Cancer. 2007 Jul 31;43(11):1670-8. 
Dougherty BE, Nichols JJ, Nichols KK. Rasch analysis of the Ocular Surface Disease 
Index (OSDI). Invest Ophthalmol Vis Sci. 2011 ;52(12): 8630-8635. 
Fayers et. al., The EORTC QLQ-C30 Scoring Manual (3rd Edition) 2001 
GlaxoSmithKline Document Number TMF-14624358 Study ID207497. DREAMM-6: A 
Phase I/II, Open-label, Dose Escalation and Expansion Study to Evaluate Safety, 
Tolerability, and Clinical Activity of the Antibody-Drug Conjugate GSK2857916 
Administered in Combination with Lenalidomide Plus Dexamethasone (Arm A), or 
Bortezomib Plus Dexamethasone (Arm B) in Participants with Relapsed / Refractory 
Multiple Myeloma – (DREAMM 6). Report Date 30-JUN-2022. 
Guglieri-Lopez B, Perez-Pitarch A, Moes DJ, Porta-Oltra B, Climente-Martí M, 
Guchelaar HJ, et al. Population pharmacokinetics of lenalidomide in multiple myeloma 
patients. Cancer Chemother Pharmacol. 2017;79:189-200 
Ji Y, Liu P, Li Y, Bekele BN. A modified toxicity probability interval method for dose-
finding trials. Clin Trials. 2010;7:653-663. 
Kumar S, et al. International Myeloma Working Group consensus criteria for response 
and minimal residual disease assessment in multiple myeloma. The Lancet Oncology. 
2016;17: e328-e346. 
Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD, et al. Development 
of the 25-item National Eye Institute Visual Function Questionnaire. Arch Ophthalmol. 
2001;119(7):1050-8. 
National Cancer Institute (NCI). CTCAE. National Cancer Institute (NCI), 
http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03; 2010. CTCAE Version 4.03. 


 
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Osoba D, Rodrigues G, Myles J, Zee B, Pater J. Interpreting the significance of changes 
in health-related quality-of-life scores. J Clin Oncol. 1998 Jan;16(1):139-44 
Proskorovsky I., P. Lewis, C. D. Williams, K. Jordan, C. Kyriakou, J. Ishak, F. E. Davies. 
Mapping EORTC QLQ-C30 and QLQ-MY20 to EQ-5D in patients with multiple 
myeloma. Health Qual Life Outcomes. 2014 Mar 11; 12:35. 
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. 
 


 
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15. 
APPENDICES 
15.1. 
Appendix 1: Assessment Windows 
No assessment windows will be applied. 
 


 
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15.2. 
Appendix 2: Study Phases and Treatment Emergent 
Adverse Events 
15.2.1. 
Study Phases 
Assessments and events will be classified according to the date/time of occurrence 
relative to date/time of first dose of study treatment.  
Study Phase 
Definition 
Pre-Treatment  
Date ≤ Study Treatment Start Date 
On-Treatment 
Study Treatment Start Date < Date ≤ Study Treatment Stop Date + 70 days 
For interim analyses when participants are still on treatment, Study Treatment Stop 
Date will be imputed following rules specified in Section 15.5.2.1. 
Post-Treatment 
Date > Study Treatment Stop Date + 70 days 
 
For assessment or event on the first dosing day, whether it is Pre-Treatment or On-
Treatment should be based on time if available. If time is not available, the first dosing 
day (Day 1) is considered Pre-Treatment for ECOG, ECG, vital signs, liver events, lab 
tests, cardiac scan, and other safety domains, and On-Treatment for adverse events and 
concomitant medications.  
Concomitant Medication and Blood and Blood Supportive Care Product 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 reference time variables and end date reference time flag 
variables will be added to the concomitant medications and blood and blood supportive 
products 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 end 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 end date is after 
the on-treatment period or (end date is missing and start relative to 
treatment='AFTER').  
Only on-treatment blood and blood supportive care products that start after the start of 
study treatment are included in the Blood Products and Blood Supportive Care Product 
summaries. Therefore, for summary tables, include blood and blood supportive care 
product records where start relative to treatment in ('DURING') and end relative to 
treatment in ('DURING','AFTER'). All data will be reported in listings.  


 
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Concomitant medication start 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 
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'). 
15.2.2. 
Study Phases for Vital signs, ECG and Laboratory Values 
Study Phase 
Definition 
Pre-Treatment  
Date ≤ Study Treatment Start Date 
On-Treatment 
Study Treatment Start Date < Date  
 
15.2.3. 
Treatment Emergent and On-treatment Flag for Adverse Events 
Table 12 
Treatment Emergent and On-treatment Flag for Adverse Events 
Flag 
Definition 
Treatment 
Emergent 
• 
Study Treatment Start Date ≤ AE Start Date ≤ min(Study Treatment Stop Date  
 + 70 days, Start of Anti-Cancer Therapy) 
• 
AE Start Date is missing 
On-treatment 
• 
Study Treatment Start Date ≤ AE Start Date ≤ Study Treatment Stop Date + 70 
days 
NOTES:  
• 
Time of study treatment dosing and start time of AEs should be considered, if collected. 
 
The “treatment emergent” definition of AEs will be used for all displays providing 
summaries by preferred term and maximum grade. All other AE displays will use the 
“on-treatment” definition.  


 
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15.3. 
Appendix 3: Data Display Standards & Handling 
Conventions 
15.3.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software will be used. 
Reporting Area 
HARP Server 
: US1SALX00259 
HARP Compound 
: arprod\gsk2859716\mid207497\ 
Analysis Datasets  
• 
Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.2 & ADaM IG 
Version 1.1).  
Generation of RTF Files 
• 
RTF files will be generated for all tables. 
 


 
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15.3.2. 
Reporting Standards 
General 
• 
The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards): 
• 
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 
• 
Note: All displays (TLF) will use the term 'Subject' to reflect GSK Display Standards and CDISC 
SDTM/ADaM standards 
Formats 
• 
GSK IDSL Statistical 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. 
• 
Reporting of data for PK related displays will be decided based on review of the data.  
• 
Numeric data will be reported at the precision collected on the eCRF. 
• 
The reported precision from non eCRF sources will follow the IDSL statistical 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 IDSL 
Statistical Principle 5.05.1). 
• 
Unscheduled or unplanned assessments will be presented within the participant’s listings.  
Unscheduled Visits 
• 
Unscheduled visits will not be included in summary tables and/or figures. 
o For by planned time analysis, unscheduled visits will not be included. 
o For worst-case analysis, unscheduled visits will be included. 
• 
All unscheduled visits will be included in listings. 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• 
Refer to IDSL Statistical Principals 7.01 to 7.13. 
 


 
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15.3.3. 
Reporting Standards for Pharmacokinetic Data 
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 
SOP_314000:  Non-Compartment Analysis of Clinical Pharmacokinetic Data [Note: 
Concentration values will be imputed as per GUI_51487] 
Descriptive Summary 
Statistics, Graphical 
Displays and Listings 
Refer to IDSL PK Display Standards. 
Refer to IDSL Statistical 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 parameters will be derived by the Programmer:  
Ctrough (predose) CEOI for each cycle, data permitting. Ctrough will not be derived 
for cys-mcMMAF. 
 
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 IDSL PK Display Standards. 
Untransformed PK 
parameter 
tmax (TMAX), tlast (TLST)  


 
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15.3.4. 
Extended Loss to Follow-up or Extended Time without an 
Adequate Assessment 
For participants, if two or more scheduled disease assessments are missed and are then 
followed by an assessment of PD or death, 
 will be censored at the last adequate 
assessment prior to PD or death. When the scheduled disease assessment is every 3 
weeks, a window of 45 days (6 weeks + 3 day window) will be used to determine 
whether there was an extended time without adequate assessment. That is, if the time 
difference between PD/death and last adequate assessment is more than 45 days, then 
 will be censored at the last adequate assessment prior to PD/death. When the 
scheduled disease assessment is every 4 weeks, a window of 59 days (8 weeks + 3 day 
window) will be used to determine whether there was an extended time without adequate 
assessment. That is, if the time difference between PD/death and last adequate assessment 
is more than 59 days, then 
will be censored at the last adequate assessment prior to 
PD/death. 
In case there is no adequate assessment between first dose date and PD/death, and the 
time difference between PD/death and first dose date is more than 45 days (when disease 
assessment is every 3 weeks), or 59 days (when disease assessment is every 4 weeks), 
then 
 will be censored at the first dose date. 
 
CCI
CCI
CCI
CCI


 
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15.3.5. 
Additional Guidance on Grading Based on Changes in Visual 
Acuity 
Baseline Vision 
(best corrected) 
Grade 1 
(Change of 1 
line from 
baseline) 
Grade 2 
(Change of 2-3 lines 
from baseline and 
not 
worse than 20/200) 
Grade 3 
(Change of more than 
3 lines from baseline 
and not worse than 
20/200) 
Grade 4 
(Worse than 20/200) 
20/20 
20/25 
20/30 – 20/40  
20/50 –20/200 
Worse than 20/200  
20/25 
20/30 
20/40 – 20/50 
20/60 –20/200 
Worse than 20/200 
20/30 
20/40 
20/50 – 20/60 
20/70 –20/200 
Worse than 20/200 
20/40 
20/50 
20/60 – 20/70 
20/80 –20/200 
Worse than 20/200 
20/50 
20/60 
20/70 – 20/80 
20/100 – 20/200 
Worse than 20/200 
20/60 
20/70 
20/80 – 20/100 
20/125 – 20/200 
Worse than 20/200 
20/70 
20/80 
20/100 – 20/125 
20/200  
Worse than 20/200 
20/80 
20/100 
20/125 – 20/200 
N/A 
Worse than 20/200 
20/100 
20/200 
20/200  
N/A 
Worse than 20/200  
 


 
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15.4. 
Appendix 4: Derived and Transformed Data 
15.4.1. 
General 
Multiple Measurements at One Analysis Time Point 
• 
Mean of the measurements will be calculated and used in any derivation of summary statistics 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.  
Study Day for Safety 
• 
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 Date ≥ First Dose Date → Study Day = Ref Date - (First Dose Date) + 1     
Study Day for Efficacy 
• 
Calculated as the number of days from [First Dose Date/Randomization Date]: 
• 
Ref Date = Missing                                                         →  Study Day = Missing  
• 
Ref Date < [First Dose Date] → Study Day = Ref Date – [First Dose Date/Randomization Date] 
o Ref Date ≥ [First Dose Date] → Study Day = Ref Date – [First Dose Date/Randomization Date] + 1   
Change from Baseline 
• 
Change from Baseline = Post-Baseline Visit Value – Baseline 
• 
% Change from Baseline= 100 x (Post-Baseline Visit Value – Baseline) / Baseline 
• 
Maximum Increase/Decrease from Baseline = maximum (Increase/Decrease from Baseline) 
• 
If either the Baseline or Post-Baseline Visit value is missing, Change from Baseline and % Change from 
Baseline is set to missing 
Date of Response 
• For post-baseline disease assessments, the date of response (PR or better) is assigned to the latest 
date of disease assessments; for other response categories (MR, SD, NE, PD), the date of response is 
assigned to the earliest date of disease assessments. 
 


 
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15.4.2. 
Study Population 
Extent of Exposure 
Number of days of exposure to study drug will be calculated based on the formula:   
o Arm A:  
▪ 
SINGLE/SPLIT Doses: Duration of Exposure = (Last Treatment Date+27) – First Treatment 
Date + 1 
▪ 
STRETCH Doses: Duration of Exposure = (Last Treatment Date+55) – First Treatment Date 
+ 1 
o Arm B:  
▪ 
SINGLE/SPLIT Doses: Duration of Exposure = (Last Treatment Date+20) – First Treatment 
Date + 1 
▪ 
STRETCH Doses: Duration of Exposure = (Last Treatment Date+41) – First Treatment Date 
+ 1 
 
• 
The cumulative dose will be based on the formula: 
Cumulative Dose (mg/kg) = Sum of Dose at Each Dosing Interval 
 
• 
Dose intensity will be calculated based on the formulas: 
o Arm A:  
▪ 
SINGLE/SPLIT Doses: Dose intensity (mg/kg/4 week)  = Cumulative Dose/((duration of 
exposure)/28) 
▪ 
STRETCH Doses: Dose intensity (mg/kg/8 week)  = Cumulative Dose/((duration of 
exposure)/56) 
o Arm B: 
▪ 
SINGLE / SPLIT Doses: Dose intensity (mg/kg/3 week)  = Cumulative Dose/((duration of 
exposure)/21) 
▪ 
STRETCH Doses: Dose intensity (mg/kg/6 week)  = Cumulative Dose/((duration of 
exposure)/42) 
 
 


 
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15.4.3. 
Safety 
Adverse Events 
AEs of Special Interest (belantamab mafodotin) 
• 
Corneal events 
• 
Thrombocytopenia 
• 
Infusion related reactions 
Duration of AE 
To report in months, divide the number of days by 30.4375; to report in weeks divide the number 
of days by 7; to report in years divide the number of days by 365.25. 
• 
Calculated as the number of days from AE Start Date to AE Stop Date: 
• 
AE Start Date = Missing              → Elapse Time = Missing  
• 
AE Stop Date = Missing              → Elapse Time = Missing 
o Otherwise                                    → Elapsed Time = AE Stop Date – AE Start Date + 1     
ECHO/MUGA 
• 
Change from Baseline for cardiac data, e.g., Left Ventricular Ejection Fraction (LVEF), will be calculated 
based on the same modality (ECHO or MUGA) throughout the study for each participant. Post-baseline 
assessments with a different cardiac scan modality will not be used to calculate change from Baseline. 
 
DLT 
DLT Evaluable 
• 
A DLT evaluable participant is defined as any participant in Part 1 who received at least 1 full dose 
of GSK2857916 and ≥75% of the planned doses of the combination with Len/Dex (Arm A), or 
Bor/Dex (Arm B) in Cycle 1 will be evaluated for DLTs using NCI-CTCAE Version 4.03 [NCI, 2010]. 
Any participant who received at least 1 full dose of belantamab mafodotin and at least 75% of 
planned doses of the respective Arm SoC (Len/Dex – Arm A or Bor/Dex – Arm B) will also be 
considered DLT-evaluable. Participants that are not DLT-evaluable will be replaced.  
 
15.4.4. 
Biomarker and/or Pharmacodynamic Data 
Pharmacodynamic biomarkers 
 
CCI


 
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15.5. 
Appendix 5: Reporting Standards for Missing Data 
15.5.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• 
A participant will be considered to have completed the study if he or she received at 
least one dose of study treatment and has progressed or died before the end of the 
study, has not been lost to Follow-up, or has not withdrawn consent from study 
participation, or the study or a treatment arm has been terminated. 
 
A participant will be considered to have withdrawn from the study if the participant has 
not died and is lost to Follow-up, or has withdrawn consent, or is no longer being 
followed at the investigator’s discretion 
 
Documentation of the cause of death in the electronic case report form (eCRF) is 
required for all participants who die in the study regardless of the cause of death. 
 
• 
Withdrawn participants for reasons other than toxicity, but prior to completion of DLT 
period will be replaced in the study. 
 
• 
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.  
 
15.5.2. 
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. 
 


 
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15.5.2.1. 
Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant listing displays. However, 
where necessary, display macros may impute dates as temporary variables for 
sorting data in listings only. In addition, partial dates may be imputed for ‘slotting’ 
data to study phases (see Section 15.2.1) or for specific analysis purposes as 
outlined below. 
• 
Imputed dates will not be used to derive study day, time to onset or duration (e.g., 
time to onset), or elapsed time variables (e.g., time since diagnosis). In addition, 
imputed dates are not used for deriving the last contact date in 
 
analysis dataset. 
Adverse Events 
• 
Imputations in the adverse events dataset are used for slotting events to the 
appropriate study time periods and for sorting in data listings. 
• 
Partial dates for AE recorded in the CRF will be imputed using the following 
conventions: 
Missing 
start day 
• 
If study treatment start date is missing (i.e., participant did not start 
study treatment), then set start date = 1st of month. 
• 
Else if study treatment start date is not missing: 
o 
If month and year of start date = month and year of study 
treatment start date, then 
▪ 
If stop date contains a full date and stop date is earlier than 
study treatment start date, then set start date= 1st of month. 
▪ 
Else set start date = study treatment start date. 
o 
Else set start date = 1st of month. 
Missing 
start day 
and month 
• 
If study treatment start date is missing (i.e., participant did not start 
study treatment), then set start date = January 1. 
• 
Else if study treatment start date is not missing: 
o 
If year of start date = year of study treatment start date, then 
▪ 
If stop date contains a full date and stop date is earlier than 
study treatment start date, then set start date = January 1. 
▪ 
Else set start date = study treatment start date. 
o 
Else set start date = January 1. 
Missing 
stop day  
Last day of the month will be used. 
Missing 
stop day 
and month 
No Imputation 
Completely 
missing 
start/end 
date 
No imputation 
Concomitant 
Medications/ 
Blood Supportive 
Products 
• 
Completely missing start dates will not be imputed 
• 
Partial start dates for any concomitant medications recorded in the CRF will be 
imputed using the following convention: 
o If day and month are missing: 
‒ If treatment start date is missing (i.e., subject did not start study 
treatment), a '01' will be used for the day and 'Jan' will be used for the 
month. 
‒ If treatment start date is not missing  
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Element 
Reporting Detail 
▪ If year of start date = year of study treatment start date 
 If stop date contains a full date which is earlier than the treatment 
start date, a '01' will be used for the day and 'Jan' will be used for 
the month. 
 else study treatment start date will be used 
▪ else a ‘01’ will be used for the day and ‘Jan’ will be used for the 
month 
‒ If medication was taken prior to study, a '01' will be used for the day and 
'Jan' will be used for the month. 
 
o If day is missing: 
‒ If treatment start date is missing (i.e., subject did not start study 
treatment), a '01' will be used for the day. 
‒ If treatment start date is not missing  
▪ If year and month of start date = year and month of study treatment 
start date 
 If stop date contains a full date which is earlier than the treatment 
start date, a '01' will be used for the day. 
 else study treatment start date will be used 
▪ else a ‘01’ will be used for the day and ‘Jan’ will be used for the 
month 
• 
Completely missing end dates will not be imputed 
• 
Partial end dates for any concomitant medications recorded in the CRF will be 
imputed using the following convention: 
o If day and month are missing 
‒ Earliest of (Dec 31st, date of last contact) will be used  
o If day is missing 
‒ Earliest of (last day of the month, date of last contact) will be used 
New Anti-Cancer 
Therapy/ 
Radiotherapy/ 
Surgical 
Procedures for 
Efficacy 
Evaluation (e.g., 
response rate, 
time to event) 
• 
Start dates for follow-up anti-cancer therapy, radiotherapy (where applicable), and 
surgical procedures (where applicable) will be imputed in order to define event 
and censoring rules for
, response rate, or
 
. Dates will only be imputed 
when a month and year are available but the day is missing. The following rules 
will be used to impute the date when partial start dates are present on anti-cancer 
therapy, radiotherapy, and/or surgical procedures dataset[s]: 
• 
Completely missing start dates will remain missing, with no imputation applied. 
• 
Partial start dates will be imputed using the following convention: 
• 
If both month and day are missing, no imputation will be applied. 
• 
If only day is missing:  
o If the month of partial date is the same as the month of last dosing date, 
minimum of (last dosing date + 1, last day of the month) will be used for 
the day. 
o If the month of partial date is the same as the month of last disease 
assessment and the last disease assessment is PD, minimum of (last 
date of disease assessment + 1, last day of the month) will be used for 
the day. 
o If both conditions above are met, the later date will be used for the day. 
o Otherwise, a ‘01’ will be used for the day. 
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Element 
Reporting Detail 
• 
Completely or partial missing end dates will remain missing, with no imputation 
applied; 
Treatment end 
date 
• 
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. 
 
For daily oral treatment:  
 
• 
In general, completely missing end dates are not imputed, with the following 
exceptions for imputation of missing treatment end date at interim analyses. 
o 
For imputation of missing exposure end date at an interim analysis when 
participants are still on treatment, the following conventions will be 
applied: 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 15.4.2.  
 
For non-continual treatment: 
• 
If treatment end date is missing for a cycle, treatment start date for the cycle 
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15.6. 
Appendix 6: Values of Potential Clinical Importance 
To identify laboratory values of potential clinical importance, National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI-CTCAE v [4.03]) will be used 
to assign grades for laboratory parameters including clinical chemistry, haematology, 
liver function tests, thyroid function tests, pancreatic enzyme tests, QTc (Bazett’s or 
Fridericia’s) values, vital signs (heart rate, blood pressure, temperature) and LVEF.  
Reference ranges for all laboratory parameters collected throughout the study are 
provided by the central laboratory, or local laboratory if applicable. 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 
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15.7. 
Appendix 7: Pharmacokinetic / Pharmacodynamic Analyses 
15.7.1. 
Pharmacokinetic / Pharmacodynamic Dataset Specification 
If deemed appropriate and if data permit, exposure-response analyses may be conducted 
using population methods to explore the relationship between exposure measures of 
belantamab mafodotin (ADC and/or cys-mcMMAF) and clinical activity and/or toxicity 
endpoints (e.g., response, AESIs).If data permit, the effects of covariates may be 
explored.  
Exposure-response analyses will use the same systems and data assembly process as 
described in Appendix 8.  
The final popPK models for both ADC and cys-mcMMAF will be applied to generate the 
following post hoc exposure measures to be used in efficacy and safety exposure-
response analyses: ADC maximum concentration (ADC Cmax), ADC trough 
concentration (ADC Ctau), ADC average concentration (ADC Cavg), cys-mcMMAF 
Cmax, and cys-mcMMAF Cavg. 
Time to events endpoints will be analyzed using Kaplan-Meier plots and cox-
proportional hazard models while probability of occurrence of event of interest will be 
evaluated using logistic regression. 
For each exposure-response analysis, univariate analysis will be performed first to 
identify the strongest individual associations of exposure and other relevant covariates to 
clinical endpoint using change in the objective function. Following the univariate 
analysis, covariate selection will be conducted using a stepwise forward inclusion and 
backward elimination method to determine the final multivariate model. Covariates 
would be retained in the model in a stepwise manner if their inclusion during forwarding 
addition decreased the objective function value (OFV) by ≥6.64 (P<0.01) over the 
previous model, with the most significant covariate being retained at each stage. This 
iterative process will continue until all significant covariates are included, thus defining 
the full model. From the full model, the significance of each covariate will be tested 
individually by removing one by one until all non-significant covariates have been 
excluded. A covariate will be retained if, upon removal, the OFV increased by more than 
10.83 points (P< 0.001). The final model is defined as the model developed following the 
backward elimination step.  
The results of these analyses may be provided in a separate report. 
15.7.2. 
Pharmacokinetic / Pharmacodynamic Methodology 
Details may be provided in a separate exposure-response analysis RAP  


 
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15.8. 
Appendix 8: Population Pharmacokinetic (PopPK) Analyses 
Belantamab mafodotin, total mAb and/or cys-mcMMAF plasma concentration-time data 
will be analyzed by Pop PK methods using a non-linear mixed-effects modelling 
approach. 
The key objective of this analysis is to: 
• 
Predict individual pharmacokinetic parameter values for belantamab mafodotin, 
and/or cys-mcMMAF 
15.8.1. 
Systems 
The population PK analysis will be performed using NONMEM (ICON Solutions) and 
PsN (Perl Speaks NONMEM) or another software platform deemed appropriate. 
Graphical displays and data summary will be produced using R (The R Foundation for 
Statistical Computing). The analysis will be performed by, or under the direct auspices 
of, Clinical Pharmacology Modelling and Simulation (CPMS), GlaxoSmithKline using 
the currently supported versions of all software packages. 
15.8.2. 
Data Assembly 
Participant data will be collected in the electronic CRF and will be transmitted into a 
validated database by GSK data management. Derived/processed variables will be 
provided by or under the guidance of Clinical Programming. Plasma samples will be 
analyzed using approved analytical methodology. Data will be transferred electronically 
to data managers to be processed and stored in the GSK database. GSK or a designated 
third party will generate the NONMEM input dataset. 
Previously generated belantamab mafodotin and/or cys-mcMMAF PK data may be 
merged with the PK data in order to provide a pooled NONMEM data set.  
15.8.3. 
Model Development 
The initial analysis will use the population pharmacokinetic model developed for Study 
BMA117159 and Study 205678; a more current population PK model may be used, if 
available. 
Initially, empirical Bayes estimates will be derived applying the current PopPK model to 
the Study 207497 dataset with the MAXEVAL=0 option. If the corresponding model 
diagnostics indicate that this PopPK model is appropriate to represent the belantamab 
mafodotin, total mAb and/or cys-mcMMAF data from Study 207497 then individual PK 
parameter estimates will be based on the current PopPK parameters.  
If the parameter set of the current PopPK model applied to the Study 207497 data set 
results in substantial bias or if a further exploration of the covariate effect in the Study 
207497 population is deemed necessary, the parameters of the current PopPK model will 
be re-estimated for the Study 207497 PK data alone before generating the individual PK 
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to the value in the current PopPK model if they cannot be estimated with sufficient 
precision within the Study 207497 PK population. Covariates not available for the Study 
207497 PK population but present in the current PopPK model may be removed from the 
Study 207497 PopPK model. Lastly, a model refinement step, if needed, will include, but 
may not be limited to, a qualification and possible modification of the model’s random 
effect structure.  
15.8.4. 
Model Qualification 
Any model development will be supported and the final model will be qualified using the 
following criteria where appropriate:  
• 
Scientific plausibility of parameter estimates 
• 
Goodness of fit plots 
• 
Relative standard errors (RSE) of the parameter estimates 
• 
Objective function value 
• 
Distribution and shrinkage of random effects. 
• 
Successful minimization and execution of covariance step 
• 
Condition number (ratio of the largest and smallest eigenvalue of the covariance 
matrix 
• 
Visual predictive check 
• 
Bootstrap (if deemed necessary/feasible) 
 


 
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15.9. 
Appendix 9: Patient Reported Outcomes 
15.9.1. 
EORTC QLQ-C30 
The EORTC QLQ-C30 is a 30-item questionnaire containing both single- and multi-item 
measures [Aaronson, 1993]. These include five functional scales (Physical, Role, 
Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and 
Nausea/Vomiting), a Global Health Status/QoL scale, and six single items (Constipation, 
Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). The below 
image shows the details. 
 
Scores for each scale and single-item measure are averaged and transformed linearly to a 
score ranging from 0–100. (See below image for details). A high score for functional 
scales and for Global Health Status/QoL represent better functioning ability or HRQoL, 
whereas a high score for symptom scales and single items represents significant 
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Scoring of the QLQ-C30 Summary Score  
The EORTC QLQ-C30 Summary Score is calculated from the mean of 13 of the 15 
QLQ-C30 scales (the Global Quality of Life scale and the Financial Impact scale are not 
included). Prior to calculating the mean, the symptom scales need to be reversed to obtain 
a uniform direction of all scales. The summary score should only be calculated if all of 
the required 13 scale scores are available.  
QLQ-C30 Summary Score = [Physical Functioning+ Role Functioning+ Social 
Functioning+ Emotional Functioning+ Cognitive Functioning+ (100- Fatigue)+ (100-
Pain)+ (100-Nausea_Vomiting)+ (100-Dyspnoea)+ (100-Sleeping Disturbances)+ (100-
Appetite Loss)+ (100-Constipation)+ (100-Diarrhoea)]/13.  
Handling of missing items 
Single-item measures: if the item is missing, the score S will be set to missing.  
Scales requiring multiple items: if at least half of the items from the scale are available, 
the score S will be calculated based on available items. If more than half of the items 
from the scale are missing, the score S will be set to missing (Fayers, 2001). 
Minimal Important Difference (MID): In a sample of patients who received 
chemotherapy for either breast cancer or small-cell lung cancer (n=246, n=80 
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up was about 5 to 10 points on a 0-100 scale for patients who indicated “a little” change 
on the Subjective Significance Questionnaire (SSQ), either for better or for worse 
(Osoba, 1998). 
15.9.2. 
EORTC QLQ-MY20 
The EORTC QLQ-MY20 is a supplement to the QLQ-C30 instrument used in patients 
with multiple myeloma [Aaronson, 1993; Cocks, 2007].  The module comprises 20 
questions that address four myeloma specific HRQoL domains: Disease Symptoms, Side 
Effects of Treatment, Future Perspective, and Body Image. Three of the four QLQ-MY20 
domains are multi-item scales: Disease Symptoms (includes bone aches or pain, back 
pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity); Side 
Effects of Treatment (includes drowsiness, thirst, feeling ill, dry mouth, hair loss, upset 
by hair loss, tingling hands or feet, restlessness/agitation, acid indigestion/heartburn, and 
burning or sore eyes); and Future Perspective (includes worry about death and health in 
the future, and thinking about illness).  The Body Image scale is a single-item scale that 
addresses physical attractiveness. (See below image for details). 
 
As with the QLQ-C30, QLQ-MY20 domain scores are also averaged and transformed 
linearly to a score ranging from 0–100 (see below for details).  
1) Raw score  
For each multi-item scale, calculate the average of the corresponding items.  
Raw Score = 𝑅𝑆= {(𝐼1+ 𝐼2+ … +𝐼𝑛)/𝑛}  
For the single-item measure, the score of the concerning item corresponds to the raw 
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2) Linear Transformation  
To obtain the Score S, standardize the raw score to a 0 – 100 range following the appropriate 
transformation:  
Symptom scales: 𝑆={(𝑅𝑆−1)/𝑟𝑎𝑛𝑔𝑒} ×100  
Functional scales: 𝑆= {1−(𝑅𝑆−1)/𝑟𝑎𝑛𝑔𝑒} ×100  
A high score for Disease Symptoms and Side Effects of Treatment represents a high level 
of symptomatology or problems, whereas a high score for Future Perspective and Body 
Image represents better outcomes [Proskorovsky, 2014].  
Missing items can be handled similarly to EORTC QLQ-C30 as described in Section 
15.9.1. 
15.9.3. 
NEI-VFQ-25 
The NEI-VFQ-25 consists of a base set of 25 vision-targeted questions representing 
11vision-related constructs, plus an additional single-item general health rating question 
[Mangione, 2001]. The NEIVFQ-25 generates the following 11 vision-targeted sub-
scales: global vision rating, difficulty with near vision activities; difficulty with distance 
vision activities; limitations in social functioning due to vision; role limitations due to 
vision; dependency on others due to vision; mental health symptoms due to vision; 
driving difficulties; limitations with peripheral vision, limitations with color vision; and 
corneal pain. 
The following two tables (from the NEI-VFQ-25 User Manuals) provide the details of 
converting the original response category to the recoded values, and items of which 
recoded values need to be averaged to generate the VFQ-25 sub-scales. Items that are left 
blank (missing data) are not taken into account when calculating the scale scores. Hence 
scores represent the average for all items in the sub-scale that the respondent answered. 
Sub-scales with at least one item answered can be used to generate a sub-scale score. To 
calculate an overall composite score for the VFQ-25, simply average the 11 vision-
targeted sub-scale scores. 
 


 
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15.10. 
Appendix 10: COVID-19 Impact 
Government or health authority enforced measures to slow the spread of COVID-19 
infection (such as lockdowns, social distancing, and travel restrictions) may have 
impacted recruitment, study treatment administration, study assessment schedule and 
subject retention.  
To understand the impact of the pandemic measures implemented at a country level, 
alerts set by the GSK country Issue Management Team (IMT) were used to determine 
when pandemic measures began. The alert levels for a country are based on multiple 
factors including government or health authority guidance advice, disease spread, and 
business/public life impact. The alert levels are escalated and de-escalated over time and 
the scale used for the recording of alerts is standardised: green (low impact), yellow (low 
to moderate impact), orange (moderate to high impact), red (high impact), and black 
(high impact with severe disruption). Date of when pandemic measures began was 
defined based on the IMT alert levels and used in analyses. 
 


 
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15.11. 
Appendix 11: Abbreviations & Trademarks 
15.11.1. 
Abbreviations 
Abbreviation 
Description 
ADA  
Anti-Drug Antibodies 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
A&R 
Analysis and Reporting  
BM 
Bone Marrow 
BMI 
Body mass index 
BOR 
Best Overall Response 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CR 
Complete Response 
CS 
Clinical Statistics 
CSR 
Clinical Study Report 
DBF 
Database Freeze 
DBR 
Database Release 
DP 
Decimal Places 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
eCRF 
Electronic Case Record Form 
eGFR 
Estimated glomerular filtration rate 
EMA 
European Medicines Agency 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Clinical Results Disclosure Requirements 
FTIH 
First Time in Human Trial 
GSK 
GlaxoSmithKline 
IA 
Interim Analysis 
ICH 
International Conference on Harmonization 
IDSL 
Integrated Data Standards Library 
IMMS 
International Modules Management System 
IMWG 
International Myeloma Working Group 
IB 
Investigational Brochure 
IP 
Investigational Product 
irAE 
Immune-related Adverse Event 
iSRC 
Internal Safety Review Committee 
ISS 
International Staging System 
LVEF 
Left ventricular ejection fraction 
MedDRA 
Medical Dictionary for Regulatory Affairs 
MR 
Minimal Response 
  
 
MTD 
Maximum Tolerated Dose 
mTPI 
modified Toxicity Probability Interval 
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Abbreviation 
Description 
MUGA 
Multigated acquisition scan 
NE 
Not Evaluable 
NCI 
National Cancer Institute 
NCI-CTCAE 
National Cancer Institute Common Toxicity Criteria for Adverse Events 
ORR 
Overall Response Rate 
PACT 
Post analysis continued treatment 
PD 
Progressive Disease 
PO 
Per os (oral) 
PK 
Pharmacokinetic 
PT 
Preferred Term 
QC 
Quality Control 
RAP 
Reporting & Analysis Plan 
RAMOS 
Randomization & Medication Ordering System  
RP2D 
Recommended Phase 2 Dose 
SAC 
Statistical Analysis Complete 
SAE 
Serious Adverse Event 
sCR 
stringent Complete Response 
SD 
Stable Disease 
SDSP 
Study Data Standardization Plan 
SDTM 
Study Data Tabulation Model 
SOC 
System Organ Classes 
SOP 
Standard Operation Procedure 
SRM 
Study Reference Manual 
SRT 
Safety Review Team 
TA 
Therapeutic Area 
TLF 
Tables, Listings, & Figures 
VGPR 
Very Good Partial Response 
 
15.11.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
ADVAIR 
 
Chiron RIBA 
 
 
SAS 
 
 
WinNonlin 
 


 
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15.12. 
Appendix 12: List of Data Displays 
15.12.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.001 to 1.xxx 
None 
Efficacy 
2.001 to 2.xxx 
2.xxx to 2.xxx 
Safety 
3.001 to 3.xxx 
3.xxx to 3.xxx 
Pharmacokinetic 
4.001 to 4.xxx 
4.xxx to 4.xxx 
Pharmacodynamic and/or Biomarker 
None 
5.xxx to 5.xxx 
Patient Reported Outcome 
6.001 to 6.xxx 
None 
Section 
Listings 
ICH Listings 
1.001 to 1.xxx 
Other Listings 
30.001 to 30.xxx 
 
15.12.2. 
Deliverables 
Delivery [Priority] [1] 
Description 
IA [1] 
Interim Analysis 1 for Arm B cohorts from Protocol Amendment 1 and 2 
Post-Interim [1] 
Re-run of cohorts from Interim [1] – select displays 
IA [2] 
Interim Analysis 2 for Arm A – all cohorts 
IA [3] 
Interim Analysis 3 for Arm B – all cohorts 
HDL [1] 
Headline Results for Final Analysis (may be completed) 
SAC [X] 
Statistical Analysis Complete for Final Analysis 
AAC [X] 
All Analysis Complete for Final Analysis 
RAPIDO DV at 
<Delivery> 
Listings that will not be reported within HDL, SAC, nor AAC, but listing 
configurations will be created to view within RAPIDO DV. 
NOTES:  
1. 
Indicates priority (i.e., order) in which displays will be generated for the reporting effort  
 


 
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15.12.3. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.001 
All Treated  
ES8 
Summary of Subject Status and Reason for Study Withdrawal (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
ICH E3, FDAAA, EudraCT 
 
Add the following categories under Subject 
Status – Ongoing: On study treatment, In 
follow-up – Alive, In follow-up – Unknown. 
 
Footnote for “On Study Treatment”: Any 
study treatment component 
 
Footnote for “In follow-up - Alive”: Subjects 
that are alive at last contact and within the 
 follow-up period. 
 
Footnote for “In follow-up – Unknown”: 
Subjects whose status is unknown at last 
contact within the 
 follow-up 
period.  
 
Footnote for “Primary Reason for study 
withdrawal”: Subjects may have only one 
primary reason for withdrawal. 
 
Footnote for “Study Terminated By Sponsor”: 
is indicative of subjects continuing into 
PACT. 
 
At SAC, add “Related to COVID-19” as 
subcategories for applicable study 
withdrawal categories. 
IA [2], HDL 
[1], SAC [1] 
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Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.002 
All Treated 
ES8 
Summary of Subject Status and Reason for Study Withdrawal (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA 
[3], HDL [1], 
SAC [1] 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.003 
All Treated 
SD4 
Summary of Treatment Status and Reasons for Discontinuation of 
GSK2857916 (Arm A – GSK2857916 + Len/Dex (Rd)) 
ICH E3 
Add footnotes: 
For “discontinued” under Treatment status: 
[1] Includes subjects who have discontinued 
treatment or died prior to End of Treatment 
Visit. 
 
For “Primary reason … “: 
[2] Subjects may have only one primary 
reason for discontinuation. 
[3] Subjects who died prior to End of 
Treatment Visit may not have a reason 
recorded. 
 
Footnote for “'Study Terminated By 
Sponsor'”: ‘Study Terminated By Sponsor’’ 
is indicative of subjects continuing into 
PACT. 
 
Add this note starting at SAC for Arm A: 
“Note: 'Protocol-Specified Withdrawal 
Criterion Met' indicates discontinuation of 
study treatment for abnormal liver tests.” 
 
At SAC, add “Related to COVID-19” as 
subcategories for applicable study 
withdrawal categories. 
IA [2], SAC 
[1] 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.004 
All Treated 
SD4 
Summary of Treatment Status and Reasons for Discontinuation of 
GSK2857916 (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
 
Add this note starting at IA [3] for Arm B: 
“Note: 'Protocol-Specified Withdrawal 
Criterion Met' indicates discontinuation of 
study treatment for abnormal liver tests.” 
IA [1], IA 
[3], SAC [1] 
1.005 
All Treated 
SD4 
Summary of Treatment Status and Reasons for Discontinuation of 
Lenalidomide (Arm A – GSK2857916 + Len/Dex (Rd)) 
Same as above 
IA [2], SAC 
[1] 
1.006 
All Treated 
SD4 
Summary of Treatment Status and Reasons for Discontinuation of Bortezomib 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above, except for different wording 
for footnote related to “Protocol-Specified 
Withdrawal Criterion Met”: 'Protocol-
Specified Withdrawal Criterion Met' indicates 
completion of protocol-specified treatment of 
Bortezomib 
IA [1], IA 
[3], SAC [1] 
1.007 
All Treated 
SD4 
Summary of Treatment Status and Reasons for Discontinuation of 
Dexamethasone (Arm A – GSK2857916 + Len/Dex (Rd)) 
Same as above 
IA [2], SAC 
[1] 
1.008 
All Treated 
SD4 
Summary of Treatment Status and Reasons for Discontinuation of 
Dexamethasone (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above, except for different wording 
for footnote related to “Protocol-Specified 
Withdrawal Criterion Met”: 'Protocol-
Specified Withdrawal Criterion Met' indicates 
completion of protocol-specified treatment of 
Dexamethasone 
IA [1], IA 
[3], SAC [1] 
1.009 
All 
Screened 
ES6 
Summary of Screening Status and Reasons for Screen Failure  
 
Journal Requirements 
 
SAC [1] 
1.010 
All Treated 
NS1 
Summary of Number of Subjects by Country and Site ID (Arm A – 
GSK2857916 + Len/Dex (Rd) 
EudraCT/Clinical Operations.  
SAC [1] 


 
CONFIDENTIAL 
 
 
 
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107 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.011 
All Treated 
NS1 
Summary of Number of Subjects by Country and Site ID (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
EudraCT/Clinical Operations.  
SAC [1] 
Protocol Deviation 
1.012 
All Treated 
DV1 
Summary of Important Protocol Deviations (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
ICH E3 
SAC [1] 
1.013 
All Treated 
DV1 
Summary of Important Protocol Deviations (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
ICH E3 
IA [3], SAC 
[1] 
1.014 
All Treated 
IE1 
Summary of Inclusion/Exclusion Criteria Deviations (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
 
SAC [1] 
1.015 
All Treated 
IE1 
Summary of Inclusion/Exclusion Criteria Deviations (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
 
SAC [1] 
1.016 
All Treated 
PAN4 
Summary of Visits impacted by COVID-19 Pandemic (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
 
SAC [1] 
1.017 
All Treated 
PAN4 
Summary of Visits impacted by COVID-19 Pandemic (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
 
SAC [1] 
Demographic and Baseline Characteristics 
1.018 
All Treated 
DM1 
Summary of Demographic Characteristics (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
ICH E3, FDAAA, EudraCT 
IA [2], SAC 
[1] 
1.019 
All Treated 
DM1 
Summary of Demographic Characteristics (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
ICH E3, FDAAA, EudraCT 
IA [1], IA 
[3], SAC [1] 
1.020 
All Treated 
DM11 
Summary of Age Ranges (Arm A – GSK2857916 + Len/Dex (Rd)) 
EudraCT 
SAC [1] 
1.021 
All Treated 
DM11 
Summary of Age Ranges (Arm B – GSK2857916 + Bor/Dex (Vd)) 
EudraCT 
SAC [1] 
1.022 
All Treated 
DM5 
Summary of Race and Racial Combinations (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
ICH E3, FDA, FDAAA, EudraCT 
SAC [1] 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.023 
All Treated 
DM5 
Summary of Race and Racial Combinations (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
ICH E3, FDA, FDAAA, EudraCT 
SAC [1] 
Disease Characteristics 


 
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109 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.024 
All Treated 
DC2 
Summary of Disease Characteristics at Screening (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
ICH E3 if collected 
Summarize Stage, Relapsed or refractory 
disease, Does the subject have 
Extramedullary Disease, Myeloma 
immunoglobulin, Does the subject have light 
chain myeloma, Type of multiple myeloma, 
Lines of therapy completed prior to 
screening, Lytic Bone Lesions, ECOG 
performance status. Include genetic 
characteristics, if collected 
 
For Lines of therapy completed prior to 
screening, display using summary statistics 
(n, mean, standard deviation, median, min, 
max). 
 
For ECOG performance status, include 
groups as 0, 1, 2 
 
Add a “missing” category to Genetics for any 
subject missing genetics information at 
screening 
 
For High Risk Cytogenetics, use the 
following groups: High-Risk (positive), Other 
(non-high risk, negative, not evaluable, not 
done). 
IA [2], HDL 
[1], SAC [1] 


 
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110 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.025 
All Treated 
DC2 
Summary of Disease Characteristics at Screening (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Same as above 
IA [1], IA 
[3], HDL [1], 
SAC [1] 
Prior and Concomitant Medications 
1.026 
All Treated 
MH1 
Summary of Current Medical Conditions (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
ICH E3  
 
SAC [1] 
1.027 
All Treated 
MH1 
Summary of Current Medical Conditions (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
ICH E3  
SAC [1] 
1.028 
All Treated 
MH1 
Summary of Past Medical Conditions (Arm A – GSK2857916 + Len/Dex (Rd)) 
ICH E3  
SAC [1] 
1.029 
All Treated 
MH1 
Summary of Past Medical Conditions (Arm B – GSK2857916 + Bor/Dex (Vd)) 
ICH E3  
SAC [1] 
1.030 
All Treated 
CM8 
Summary of Concomitant Medications (Arm A – GSK2857916 + Len/Dex (Rd)) 
ICH E3 include ‘medications taken on-
treatment (including those started prior to 
treatment), and ‘‘Medications that started on 
treatment’  
 
Column 1 by “Ingredient-Route” 
 
SAC [1] 
1.031 
All Treated 
CM8 
Summary of Concomitant Medications (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
SAC [1] 
Prior Anti-Cancer Therapy 
1.032 
All Treated 
AC2 
Summary of Prior Anti-Cancer Therapy by Drug Class of Agents (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
See Table 1.0200 in Study 205678 
(primary_01). 
 
Add footnote:  
Note: Subjects may be included in more than 
one category. 
IA [2], SAC 
[1] 
1.033 
All Treated 
AC2 
Summary of Prior Anti-Cancer Therapy by Drug Class of Agents (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA 
[3], SAC [1] 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Exposure and Treatment Compliance 


 
CONFIDENTIAL 
 
 
 
207497 
 
112 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.034 
All Treated 
OEX1 
Summary of Exposure to GSK2857916 (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
*Include “Time on Study Treatment (weeks)”; 
“Dose Intensity (mg/kg/4 weeks)”; n, Mean, 
SD, Median, Min, Max; Relative Dose 
Intensity (%).  
 
*See definition of Dose Intensity in Section 
6.5 
 
*Label Dose Intensity as (mg/kg/interval), 
with a footnote for interval to state “interval is 
4 weeks for SINGLE and SPLIT dosing and 
8 weeks for STRETCH dosing.” 
 
Footnotes: 
[1] The time on study treatment does not 
exclude dose interruptions. 
[2] Interval is 4 weeks for SINGLE and SPLIT 
dosing, and 8 weeks for STRETCH and S/D 
STRETCH dosing. 
[3] dose intensity, date of discontinuation is 
the date of last dose. 
[4] Relative dose intensity (Dose 1) is 
calculated as a percent and is defined as 
100*(mean overall Dose Intensity for Dose 1 
divided by planned dose intensity for Dose 
1). 
[5] Relative dose intensity (post-Dose 1) is 
calculated as a percent and is defined as 
100*(mean overall Dose Intensity post Dose 
1 divided by planned dose intensity post 
Dose 1). 
IA [2], SAC 
[1] 


 
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113 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.035 
All Treated 
OEX1 
Summary of Exposure to GSK2857916 (Arm B – GSK2857916 + Bor/Dex (Vd)) 
*Include “Time on Study Treatment (weeks)”; 
“Dose Intensity (mg/kg/4 weeks)”; n, Mean, 
SD, Median, Min, Max; Relative Dose 
Intensity (%) 
 
*For S/D Stretch dose, DI and RDI 
calculations for post-C1D1 only.  
 
*See definition of Dose Intensity in Section 
6.5 
 
*Label Dose Intensity as (mg/kg/interval), 
with a footnote for interval to state “interval is 
3 weeks for SINGLE and SPLIT doses and 6 
weeks for STRETCH and S/D STRECH 
doses.” 
 
Footnotes: 
[1] The time on study treatment does not 
exclude dose interruptions. 
[2] Interval is 3 weeks for SINGLE and SPLIT 
dosing, and 6 weeks for STRETCH and S/D 
STRETCH dosing. 
[3] For dose intensity, date of discontinuation 
is the date of last dose. 
[4] Relative dose intensity (Dose 1) is 
calculated as a percent and is defined as 
100*(mean overall Dose Intensity for Dose 1 
divided by planned dose intensity for Dose 
1). 
[5] Relative dose intensity (post-Dose 1) is 
calculated as a percent and is defined as 
100*(mean overall Dose Intensity post Dose 
1 divided by planned dose intensity post 
Dose 1). 
Note: ID 801 (GSK916 2.5mg/kg SPLIT + Vd 
cohort) was dosed with 2.5 mg/kg of 
GSK2857916 on Day 1 and 8. 
 
IA [1], Post-
Interim [1], 
IA [3], SAC 
[1] 


 
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114 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.036 
All Treated 
OEX1 
Summary of Exposure to Lenalidomide (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
Same as above 
 
Within the table, separate out the calculation 
to create dose intensity for subjects who’s 
first dose was 25mg, vs. those whose first 
dose was 10mg. Therefore, we will have 2 DI 
calculations (first dose 25mg and first dose 
10mg). We will still have 1 Relative DI 
calculation 
 
At SAC add:  
Time on Study Treatment (weeks) [1] 
Dose Intensity (mg/4 weeks)– 10mg [2] 
Dose Intensity (mg/4 weeks) – 25mg [2] 
Relative Dose Intensity [3] 
 
Footnotes:  
[1] The time on study treatment does not 
exclude dose interruptions. 
[2] For dose intensity, date of discontinuation 
is the date of last dose. 
[3] Relative dose intensity is calculated as a 
percent and is defined as 
100*(mean overall Dose Intensity divided by 
planned dose intensity). 
Note: Lenalidomide is administered as 
25mg/day in subjects with eGFR >=60 
mL/min/1.73 m^2. 
The dose of lenalidomide is reduced to 
10mg/day in subjects with eGFR of 40-60 
mL/min/1.73 m^2. 
 
IA [2], SAC 
[1] 


 
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115 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.037 
All Treated 
OEX1 
Summary of Exposure to Bortezomib (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Add:  
Time on Study Treatment (weeks) [1] 
Dose Intensity (mg/m2/3 weeks) [2] 
Relative Dose Intensity [3] 
 
Footnotes:  
[1] The time on study treatment does not 
exclude dose interruptions. 
[2] For dose intensity, date of discontinuation 
is the date of last dose. 
[3] Relative dose intensity is calculated as a 
percent and is defined as 
100*(mean overall Dose Intensity divided by 
planned dose intensity). 
 
IA [1], IA 
[3], SAC [1] 


 
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116 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.038 
All Treated 
OEX1 
Summary of Exposure to Dexamethasone (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
Within the table, separate out the calculation 
to create dose intensity for subjects who’s 
first dose was 20mg, vs. those whose first 
dose was 40mg. Therefore, we will have 2 DI 
calculations (first dose 20mg and first dose 
40mg). We will still have 1 Relative DI 
calculation 
 
Add:  
Time on Study Treatment (weeks) [1] 
Dose Intensity (mg/4 weeks) – 20mg [2] 
Dose Intensity (mg/4 weeks)– 40mg [2] 
Relative Dose Intensity [3] 
 
Footnotes:  
[1] The time on study treatment does not 
exclude dose interruptions. 
[2] For dose intensity, date of discontinuation 
is the date of last dose. 
[3] Relative dose intensity is calculated as a 
percent and is defined as 
100*(mean overall Dose Intensity divided by 
planned dose intensity). 
SAC [1] 


 
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117 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.039 
All Treated 
OEX1 
Summary of Exposure to Dexamethasone (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
Within the table, separate out the calculation 
to create dose intensity for subjects who’s 
first dose was 10mg, vs. those whose first 
dose was 20mg. Therefore, we will have 2 DI 
calculations (first dose 20mg and first dose 
40mg). We will still have 1 Relative DI 
calculation 
 
Add:  
Time on Study Treatment (weeks) [1] 
Dose Intensity (mg/3 weeks) – 10mg  [2] 
Dose Intensity (mg/3 weeks) – 20mg [2] 
Relative Dose Intensity [3] 
 
Footnotes:  
[1] The time on study treatment does not 
exclude dose interruptions. 
[2] For dose intensity, date of discontinuation 
is the date of last dose. 
[3] Relative dose intensity is calculated as a 
percent and is defined as 
100*(mean overall Dose Intensity divided by 
planned dose intensity). 
 
SAC [1] 


 
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118 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.040 
All Treated 
ODMOD1 Summary of Dose Reductions of GSK2857916 (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
*Replace “Planned Time” with “Visit” for 
“Number of Subjects with Dose Reduction by 
Planned Time.” 
 
*Add footnotes:  
For Arm A, each cycle is 4 weeks (28 days) 
No dose reduction of GSK2857916 allowed 
for 1.9 mg/kg STRETCH and SINGLE 
IA [2], SAC 
[1] 
1.041 
All Treated 
ODMOD1 Summary of Dose Reductions of GSK2857916 (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
*Replace “Planned Time” with “Visit” for 
“Number of Subjects with Dose Reduction by 
Planned Time.” 
 
*Add footnotes:  
For Arm B, each cycle is 3 weeks (21 days) 
No dose reduction of GSK2857916 allowed 
for 1.9 mg/kg STRETCH and SINGLE, and 
2.5 mg/kg S/D STRETCH 
IA [1], IA 
[3], SAC [1] 


 
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119 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.042 
All Treated 
ODMOD3 Summary of Dose Delays of GSK2857916 (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
*Replace “Planned Time” with “Visit” for 
“Number of Subjects with Dose Delays by 
Planned Time.” 
 
Under “Delay Duration (days)” use the 
following groups: 1-28, 29-56, >56 
 
*Add a footnote: “For Arm A, each cycle is 4 
weeks (28 days)” 
 
*Add the following note in the footnotes: 
Note: From the Exposure eCRF, dose delays 
are defined when a dose modification has 
been indicated as “Delay”. For the “Adverse 
Event” category under “Primary Reason”, 
these events correspond to the GSK2857916 
Exposure eCRF where primary reason has 
been recorded as Adverse Event. 
IA [2], SAC 
[1] 


 
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120 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.043 
All Treated 
ODMOD3 Summary of Dose Delays of GSK2857916 (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
*Replace “Planned Time” with “Visit” for 
“Number of Subjects with Dose Delays by 
Planned Time.” 
 
Under “Delay Duration (days)” use the 
following groups: 1-21, 22-42, >42 
 
*Add a footnote: “For Arm B, each cycle is 3 
weeks (21 days)” 
 
*Add the following note in the footnotes: 
Note: From the Exposure eCRF, dose delays 
are defined when a dose modification has 
been indicated as “Delay”. For the “Adverse 
Event” category under “Primary Reason”, 
these events correspond to the GSK2857916 
Exposure eCRF where primary reason has 
been recorded as Adverse Event. 
IA [1], IA 
[3], SAC [1] 
1.044 
All Treated 
ODMOD5 Summary of Primary Reason for Dose Reductions of GSK2857916 by Visit 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
*Changed “planned time” columns to “visit” 
 
*Add footnotes:  
For Arm A, each cycle is 4 weeks (28 days) 
No dose reduction of GSK2857916 allowed 
for 1.9 mg/kg STRETCH and SINGLE 
IA [2], SAC 
[1] 


 
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121 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.045 
All Treated 
OEX6 
Summary of Dose Intensity of GSK2857916 by Expected Duration of Exposure 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
*This display was created for IA [1] and Post 
Interim [1] only. After Post-Interim [1], this 
display was removed, hence the re-
numbering of displays.  
 
This is a summary of dose intensity by a 
patient’s actual or expected duration of 
exposure for Arm A (Q4W).  
 
*Add footnotes:  
[1] Dose intensity is the cumulative actual 
dose divided by duration of exposure (or 
expected duration of exposure) in 
mg/kg/4weeks. 
Note: For Arm A, expected duration of 
exposure is every 4 weeks (28 days). 
IA [1], Post 
Interim [1] 
1.045 
All Treated 
ODMOD5 Summary of Primary Reason for Dose Reductions of GSK2857916 by Visit 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
*Changed “planned time” columns to “visit” 
 
*Add footnotes:  
For Arm B, each cycle is 3 weeks (21 days) 
No dose reduction of GSK2857916 allowed 
for 1.9 mg/kg STRETCH and SINGLE, and 
2.5 mg/kg S/D STRETCH 
IA [1], IA 
[3], SAC [1] 


 
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122 
 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.046 
All Treated 
ODMOD6 Summary of Primary Reason for Dose Delays of GSK2857916 by Visit (Arm A 
– GSK2857916 + Len/Dex (Rd)) 
*Changed “planned time” columns to “visit” 
 
*Add a footnote: “For Arm A, each cycle is 4 
weeks (28 days)” 
 
*Add the following note in the footnotes: 
Note: From the Exposure eCRF, dose delays 
are defined when a dose modification has 
been indicated as “Delay”. For the “Adverse 
Event” category under “Primary Reason”, 
these events correspond to the GSK2857916 
Exposure eCRF where primary reason has 
been recorded as Adverse Event. 
IA [2], SAC 
[1] 
1.047 
All Treated 
ODMOD6 Summary of Primary Reason for Dose Delays of GSK2857916 by Visit (Arm B 
– GSK2857916 + Bor/Dex (Vd)) 
Same as above, except for the following 
footnote:  
 
*Add a footnote: “For Arm B, each cycle is 3 
weeks (21 days)” 
IA [1], IA 
[3], SAC [1] 
Duration of Follow-up 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.048 
All Treated 
FAC2 
Summary of Duration of Follow-Up (Arm A – GSK2857916 + Len/Dex (Rd)) 
Add a Total column at SAC [1] 
 
Footnotes:  
[1] Duration of Follow-Up is defined as the 
time from first dose to last contact or death. 
[2] Subjects with ongoing Follow-Up are 
those within the 
 Follow-Up 
period, with status Alive or Unknown 
 
For SAC, do not report subjects with ongoing 
follow-up, as participants are moving into 
PACT. 
IA [2], SAC 
[1] 
1.049 
All Treated 
FAC2 
Summary of Duration of Follow-Up (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
 
Add a Total column at IA [3] and SAC [1] 
IA [3], SAC 
[1] 
Blood and Blood Supportive Care Products 
1.050 
All Treated 
BP1A 
Summary of Blood Products (Arm A – GSK2857916 + Len/Dex (Rd)) 
 
SAC [1] 
1.051 
All Treated 
BP1A 
Summary of Blood Products (Arm B – GSK2857916 + Bor/Dex (Vd)) 
 
SAC [1] 
1.052 
All Treated 
BP1C 
Summary of Blood Supportive Care Products (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
 
SAC [1] 
1.053 
All Treated 
BP1C 
Summary of Blood Supportive Care Products (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
 
SAC [1] 
Substance Use 
1.054 
All Treated 
SU1 
Summary of Substance Use (Arm A – GSK2857916 + Len/Dex (Rd)) 
 
SAC [1] 
1.055 
All Treated 
SU1 
Summary of Substance Use (Arm B – GSK2857916 + Bor/Dex (Vd)) 
 
SAC [1] 
CCI


 
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15.12.4. 
Efficacy Tables 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Responses  
2.001 
All Treated 
RE1a 
Summary of Investigator-Assessed Best Response with 
confirmation (IMWG criteria) (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
Best Response: Stringent Complete 
Response (sCR), Complete response 
(CR), Very Good Partial Response 
(VGPR), Partial Response (PR), 
Minimal Response (MR), Stable 
Disease (SD), Progressive Disease 
(PD), Not Evaluable (NE). 
 
*Display each of the summaries below 
in this order: 
 
: 
(sCR+CR+VGPR+PR+MR) 
 
Overall Response Rate: 
(sCR+CR+VGPR+PR) 
):  
(sCR+CR) 
 
Footnote: The 95% Confidence Interval 
is based on Exact method. 
IA [2], HDL [1], 
SAC [1] 
CCI
CCI
CCI


 
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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.002 
All Treated 
RE1a 
Summary of Investigator-Assessed Best Response with 
confirmation (IMWG criteria) (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
Same as above 
Post-Interim [1], 
IA [1], IA [3], 
HDL [1], SAC 
[1] 
Time-to-Event 
2.003 
All Treated 
TTE1a 
Summary of 
 Based on Investigator-Assessed 
Response (Arm A – GSK2857916 + Len/Dex (Rd)) 
Among responders only 
 
Add footnote:  
SAC [1] 
2.004 
All Treated 
TTE1a 
Summary of 
 Based on Investigator-Assessed 
Response (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [3], SAC [1] 
2.005 
All Treated 
TTE1a 
Summary of 
 Based on Investigator-
Assessed Response (Arm A – GSK2857916 + Len/Dex (Rd)) 
Among responders only 
 
Add footnote:  
SAC [1] 
2.006 
All Treated 
TTE1a 
Summary of 
 Based on Investigator-
Assessed Response (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
SAC [1] 
CCI
CCI
CCI
CCI
CCI
CCI


 
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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.007 
All Treated 
TTE1a 
Summary of 
 Based on Investigator-
Assessed Response (Arm A – GSK2857916 + Len/Dex (Rd)) 
Among responders only 
 
Add footnote:  
 
 
 
 is 
documented per IMWG; or death due to 
PD occurs among participants who 
achieve an overall response, i.e., 
confirmed PR or better. 
 
Include the estimated 
probability 
at Month 4 at interim and Month 6, 9, 
12, and 18 at final analysis. 
IA [2], HDL [1], 
SAC [1] 
2.008 
All Treated 
TTE1a 
Summary of 
 Based on Investigator-
Assessed Response (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [3], HDL [1], 
SAC [1] 
2.009 
All Treated 
TTE1a 
Summary of 
 Based on  Investigator-
Assessed Response  (Arm A – GSK2857916 + Len/Dex (Rd)) 
Include the estimated 
 probability at 
Month 4 at interim and Month 6, 9, 12, 
and 18 at final analysis. 
 
Footnotes:  
[1] Confidence Intervals estimated 
using the Brookmeyer Crowley method. 
Note:
 is 
defined as the time from first dose until 
the earliest date of confirmed 
disease progression (PD) per IMWG, or 
death due to any cause. 
IA [2], HDL [1], 
SAC [1] 
CCI
CCI
CCI
CCI
CCI
CCI
CCI


 
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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.010 
All Treated 
TTE1a 
Summary of 
 Based on  Investigator-
Assessed Response  (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [3], HDL [1], 
SAC [1] 
2.011 
All Treated 
TTE1a 
Summary of 
 Based on  Investigator-
Assessed Response  (Arm A – GSK2857916 + Len/Dex (Rd)) 
Footnotes: 
[1] Confidence Intervals estimated 
using the Brookmeyer Crowley method. 
Note: 
 
 
 
per IMWG, or death due to PD. 
SAC [1] 
2.012 
All Treated 
TTE1a 
Summary of 
 Based on  Investigator-
Assessed Response  (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
SAC [1] 
2.013 
All Treated 
TTE1a 
Summary of 
 (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
Include the estimated 
probability at 
Month 4 at interim and Month 6, 9, 12, 
and 18 at final analysis. 
 
Footnotes:  
[1] Confidence Intervals estimated 
using the Brookmeyer Crowley method. 
Note: 
 
 
. 
IA [2], SAC [1] 
2.014 
All Treated 
TTE1a 
Summary of 
 (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
Same as above 
IA [3], SAC [1] 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI


 
CONFIDENTIAL 
 
 
 
207497 
 
128 
 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
See Table 2.4 in Study 207503 
(internal_02). 
 
For each dose group (Inv-Assessed 
only):  
• 
 and 95% 
Confidence Interval for sCR/CR 
and sCR/CR/VGPR groups.  
• 
Add small n for “
 Data 
Available” to reflect number of 
subjects with any 
 data.  
CCI
CCI
CCI
CCI


 
CONFIDENTIAL 
 
 
 
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129 
 
15.12.5. 
Efficacy Figures 
Efficacy: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Response 
2.017 
All Treated 
Programming 
note 
Forest Plot - Overall Response Rate (ORR) Based on  
Investigator-Assessed-Assessed Response (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Similar to Figure 2.0020 in Study 
205678 (primary_01).  
 
See Section 5.3.1 for the subgroups to 
be included.  
 
Create one Forest Plot for all doses 
combined, and then a second Forest 
Plot for the 2.5 mg/kg SINGLE dose 
only.  
SAC [1] 
2.018 
All Treated 
 
Programming 
note 
Forest Plot - Overall Response Rate (ORR) Based on 
Investigator-Assessed Response (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Same as above 
SAC [1] 
Time-to-Event 
2.019 
All Treated 
TTE10 
Graph of Kaplan Meier Curves of 
 
Based on Investigator-Assessed Response (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Labels:  
X-axis: Time since 
 
 (Months) 
Y-axis: Proportion Alive and 
 
SAC [1] 
2.020 
All Treated 
TTE10 
Graph of Kaplan Meier Curves of 
 
Based on Investigator-Assessed Response (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Labels:  
X-axis: Time since 
 
(Months) 
Y-axis: Proportion Alive and 
 
SAC [1] 
CCI
CCI
CCI
CCI
CCI
CCI


 
CONFIDENTIAL 
 
 
 
207497 
 
130 
 
Efficacy: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.021 
All Treated 
TTE10 
Graph of Kaplan Meier Curves of 
 
Based on Investigator-Assessed Response (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Labels: 
X-axis: Time since Treatment Start 
Date (Months) 
Y-axis: Proportion Alive and 
 
SAC [1] 
2.022 
All Treated 
TTE10 
Graph of Kaplan Meier Curves of 
 
Based on Investigator-Assessed Response (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Labels: 
X-axis: Time since Treatment Start 
Date (Months) 
Y-axis: Proportion Alive and 
 
SAC [1] 
2.023 
All Treated 
TTE10 
Graph of Kaplan Meier Curves of 
 Based 
on Investigator-Assessed Response (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
Labels: 
X-axis: Time since Treatment Start 
Date (Months) 
Y-axis: Proportion Alive and 
 
SAC [1] 
2.024 
All Treated 
TTE10 
Graph of Kaplan Meier Curves of 
 Based 
on Investigator-Assessed Response (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Labels: 
X-axis: Time since Treatment Start 
Date (Months) 
Y-axis: Proportion Alive and 
 
SAC [1] 
2.025 
All Treated 
TTE10 
Graph of Kaplan Meier Curves of 
Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Labels: 
X-axis: Time since Treatment Start 
Date (Months) 
Y-axis: 
 
SAC [1] 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI


 
CONFIDENTIAL 
 
 
 
207497 
 
131 
 
Efficacy: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.026 
All Treated 
TTE10 
Graph of Kaplan Meier Curves of 
 (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Labels: 
X-axis: Time since Treatment Start 
Date (Months) 
Y-axis: 
 
SAC [1] 
 
 
CCI
CCI


 
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132 
 
15.12.6. 
Safety Tables 
Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
Adverse Events (AEs) 
3.001 
All Treated 
AE13 
Adverse Event Overview (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
See mock in Section 15.13 with categories 
and footnotes to include. In shell, for rows 
that state “Lenalidomide/Bortezomib” – use 
“Lenalidomide” for Arm A. 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
 
Add footnote:  
No dose reduction of GSK2857916 allowed 
for 1.9 mg/kg STRETCH and SINGLE  
IA [2], HDL [1], SAC [1] 
3.002 
All Treated 
AE13 
Adverse Event Overview (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
See mock in Section 15.13 with categories 
and footnotes to include. In shell, for rows 
that state “Lenalidomide/Bortezomib” – use 
“Bortezomib” for Arm B. 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
 
Add footnote:  
No dose reduction of GSK2857916 allowed 
for 1.9 mg/kg STRETCH and SINGLE, and 
2.5 mg/kg S/D STRETCH 
IA [1], IA [3], HDL 
[1],SAC [1] 
3.003 
All Treated 
OAE07 
Summary of Adverse Events by Preferred Term and 
Maximum Grade (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
Add summary over all cohorts 
IA [2], HDL [1], SAC [1] 


 
CONFIDENTIAL 
 
 
 
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133 
 
Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.004 
All Treated 
OAE07 
Summary of Adverse Events by Preferred Term and 
Maximum Grade (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
Add summary over all cohorts 
IA [1], IA [3], HDL [1], 
SAC [1] 
3.005 
All Treated 
OAE07 
Summary of Adverse Events Related to GSK2857916 
by Preferred Term and Maximum Grade (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Add footnote: 
 
‘Related to GSK2857916 includes responses 
of ‘Yes’ only, to the following question: ‘Is 
there a reasonable possibility that the AE 
may have been caused by the study 
treatment?’ for GSK2857916 
 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
IA [2], SAC [1] 
3.006 
All Treated 
OAE07 
Summary of Adverse Events Related to GSK2857916 
by Preferred Term and Maximum Grade (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
SAC [1] 
3.007 
All Treated 
OAE07 
Summary of Adverse Events Related to Lenalidomide 
by Preferred Term and Maximum Grade (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
‘Related to Lenalidomide includes responses 
of ‘Yes’ only, to the following question: ‘Is 
there a reasonable possibility that the AE 
may have been caused by the study 
treatment?’ for Lenalidomide 
 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
SAC [1] 
3.008 
All Treated 
OAE07 
Summary of Adverse Events Related to Bortezomib by 
Preferred Term and Maximum Grade (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
‘Related to Bortezomib includes responses 
of ‘Yes’ only, to the following question: ‘Is 
there a reasonable possibility that the AE 
may have been caused by the study 
treatment?’ for Bortezomib 
 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
SAC [1] 


 
CONFIDENTIAL 
 
 
 
207497 
 
134 
 
Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.009 
All Treated 
OAE07 
Summary of Adverse Events Related to 
Dexamethasone by Preferred Term and Maximum 
Grade (Arm A – GSK2857916 + Len/Dex (Rd)) 
‘Related to Dexamethasone includes 
responses of ‘Yes’ only, to the following 
question: ‘Is there a reasonable possibility 
that the AE may have been caused by the 
study treatment?’ for Dexamethasone 
 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
SAC [1] 
3.010 
All Treated 
OAE07 
Summary of Adverse Events Related to 
Dexamethasone by Preferred Term and Maximum 
Grade (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
SAC [1] 
3.011 
All Treated 
OAE07 
Summary of Adverse Events Related to Study 
Treatment by Preferred Term and Maximum Grade 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
‘Related to Study Treatment’ includes 
responses of ‘Yes’ and missing responses to 
the following question: ‘Is there a reasonable 
possibility that the AE may have been 
caused by the study treatment?’ 
 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
 
Include a footnote: 
AEs related to at least one component of 
study treatment are included.  
IA [2], SAC [1] 
3.012 
All Treated 
OAE07 
Summary of Adverse Events Related to Study 
Treatment by Preferred Term and Maximum Grade 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
SAC [1] 
3.013 
All Treated 
AE3 
Summary of Adverse Events of Maximum Grade 3 or 
Higher by Preferred Term (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
IA [2], SAC [1] 


 
CONFIDENTIAL 
 
 
 
207497 
 
135 
 
Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.014 
All Treated 
AE3 
Summary of Adverse Events of Maximum Grade 3 or 
Higher by Preferred Term (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
IA [1], IA [3],  
SAC [1] 
3.015 
All Treated 
AE1 
Summary of All Adverse Events by System Organ 
Class and Preferred Term (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
ICH E3 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
IA [2], SAC [1] 
3.016 
All Treated 
AE1 
Summary of All Adverse Events by System Organ 
Class and Preferred Term (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
ICH E3 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
IA [1], IA [3],  
SAC [1] 
3.017 
All Treated 
AE3 
Summary of Common (>=5%) Adverse Events by 
Preferred Term (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
ICH E3 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
SAC [1] 
3.018 
All Treated 
AE3 
Summary of Common (>=5%) Adverse Events by 
Preferred Term (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
ICH E3 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
SAC [1] 
3.019 
All Treated 
AE15 
Summary of Common (>=5%) Non-serious Adverse 
Events by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences) (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
FDAAA, EudraCT 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
SAC [1] 
3.020 
All Treated 
AE15 
Summary of Common (>=5%) Non-serious Adverse 
Events by System Organ Class and Preferred Term 
(Number of Subjects and Occurrences) (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
FDAAA, EudraCT  
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
SAC [1] 
3.021 
All Treated 
AE3 
Summary of Common (>=5%) Grade 3+ Adverse 
Events by Preferred Term (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
ICH E3 
Use definition of on-treatment AEs as seen 
in Section15.2.3 
SAC [1] 


 
CONFIDENTIAL 
 
 
 
207497 
 
136 
 
Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.022 
All Treated 
AE3 
Summary of Common (>=5%) Grade 3+ Adverse 
Events by Preferred Term (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
ICH E3 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
SAC [1] 
3.023 
All Treated 
AE3 
Summary of Common (>=5%) Drug-Related Grade 
3+Adverse Events by Preferred Term (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
ICH E3 
*Drug-Related = GSK2857916, Len, and/or 
Dex 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
SAC [1] 
3.024 
All Treated 
AE3 
Summary of Common (>=5%) Drug-Related Grade 3+ 
Adverse Events by Preferred Term (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
*Drug-Related = GSK2857916, BOR, and/or 
Dex 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
SAC [1] 
3.025 
All Treated 
PAN1A 
Number of subjects with suspected, probable or 
confirmed for COVID-19 infection (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
 
SAC [1] 
3.026 
All Treated 
PAN1A 
Number of subjects with suspected, probable, or 
confirmed for COVID-19 infection (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
 
SAC [1] 
Serious and Other Significant Adverse Events 
3.027 
All Treated 
AE3 
Summary of Serious Adverse Events (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Use definition of on-treatment AEs as seen 
in Section 15.2.3. Sort in descending order of 
total incidence.  
IA [2], SAC [1] 
3.028 
All Treated 
AE3 
Summary of Serious Adverse Events (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Use definition of on-treatment AEs as seen 
in Section 15.2.3. Sort in descending order of 
total incidence. 
IA [1], IA [3],  
SAC [1] 


 
CONFIDENTIAL 
 
 
 
207497 
 
137 
 
Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.029 
All Treated 
OAE07 
Summary of Serious Adverse Events Related to 
GSK2857916 by Preferred Term and Maximum Grade 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
Add footnote:  
 
‘Related to GSK2857916 includes responses 
of ‘Yes’ only, to the following question: ‘Is 
there a reasonable possibility that the SAE 
may have been caused by the study 
treatment?’ for GSK2857916 
 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
 
Add summary over all cohorts 
IA [2], SAC [1] 
3.030 
All Treated 
OAE07 
Summary of Serious Adverse Events Related to 
GSK2857916 by Preferred Term and Maximum Grade 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [3], SAC [1] 
3.031 
All Treated 
AE3 
Summary of AEs Leading to Permanent 
Discontinuation of Study Treatment by Preferred Term 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
IA [2], SAC [1] 
3.032 
All Treated 
AE3 
Summary of AEs Leading to Permanent 
Discontinuation of Study Treatment by Preferred Term 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
IA [1], IA [3],  
SAC [1] 


 
CONFIDENTIAL 
 
 
 
207497 
 
138 
 
Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.033 
All Treated 
AE3 
Summary of Adverse Events Leading to Dose 
Reductions/Interruptions/Delays (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
*Add the following notes in the footnotes: 
Note: This summary includes responses of 
“Dose reduced”, “Dose interrupted/delayed”, 
and “Infusion stopped early and not 
completed”, to the following question: “Were 
any action(s) taken with GSK2857916 (also 
Lenalidomide and Dexamethasone) as a 
result of the AE?” from the AE eCRF. 
 
No dose reduction of GSK2857916 allowed 
for 1.9 mg/kg STRETCH and SINGLE  
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
IA [2], SAC [1] 
3.034 
All Treated 
AE3 
Summary of Adverse Events Leading to Dose 
Reductions/Interruptions/Delays (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
*Add the following notes in the footnotes: 
Note: This summary includes responses of 
“Dose reduced”, “Dose interrupted/delayed”, 
and “Infusion stopped early and not 
completed”, to the following question: “Were 
any action(s) taken with GSK2857916 (also 
Bortezomib and Dexamethasone) as a result 
of the AE?” from the AE eCRF. 
 
No dose reduction of GSK2857916 allowed 
for 1.9 mg/kg STRETCH and SINGLE, and 
2.5 mg/kg S/D STRETCH 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
IA [1], IA [3],  
SAC [1] 


 
CONFIDENTIAL 
 
 
 
207497 
 
139 
 
Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
Adverse Events of Special Interest 
3.035 
All Treated 
ESI1 
Summary of Characteristics of Corneal Events 
(Overall GSK scale) (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
See mock in Section 15.13 with categories 
and footnotes to include. 
 
 
 
IA [2], HDL [1], SAC [1] 
3.036 
All Treated 
ESI1 
Summary of Characteristics of Corneal Events 
(Overall GSK scale) (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
Same as above 
 
Also, add a footnote:  
For IDs 2, 3, 6 (Arm B 2.5 mg/kg SINGLE), 
total number of adverse events may be 
overreported due to a site related unfixable 
non-standard logging of ongoing events. 
IA [1], Post-Interim [1], 
IA [3], HDL [1], 
SAC [1] 
3.037 
All Treated 
AE13_GSK 
Corneal Event Overview (Overall GSK Scale) (Arm A 
– GSK2857916 + Len/Dex (Rd)) 
See mock in Section 15.13 with categories 
and footnotes to include 
 
Add footnote:  
No dose reduction of GSK2857916 allowed 
for 1.9 mg/kg STRETCH and SINGLE  
IA [2], SAC [1] 
3.038 
All Treated 
AE13_GSK 
Corneal Event Overview (Overall GSK Scale) (Arm B 
– GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], Post-Interim [1], 
IA [3],  
SAC [1] 
3.039 
All Treated 
ESI2b 
Summary of Onset and Duration of the First 
Occurrence of Corneal Events (Overall GSK Scale) of 
Grade 2 or Above (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
Time of onset: 1-28, 29-56, 57-84, >84. 
Duration: 1-28, 29-56, >56. Mean, SD, 
Median, Min, Max 
IA [2], SAC [1] 


 
CONFIDENTIAL 
 
 
 
207497 
 
140 
 
Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.040 
All Treated 
ESI2b 
Summary of Onset and Duration of the First 
Occurrence of Corneal Events (Overall GSK Scale) of 
Grade 2 or Above (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
Same as above, except for Time of Onset 
and Duration groups: 
Time of onset: 1-21, 22-42, 43-63, >63. 
Duration: 1-21, 22-42, >42. Mean, SD, 
Median, Min, Max 
IA [1], Post-Interim [1], 
IA [3],  
SAC [1] 
3.041 
All Treated 
SAFE_T2a 
Summary of Corneal Events (Overall GSK Scale) 
Leading to Action Taken with GSK2857916 (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
 
IA [2], SAC [1] 
3.042 
All Treated 
SAFE_T2a 
Summary of Corneal Events (Overall GSK Scale) 
Leading to Action Taken with GSK2857916 (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
 
IA [1], IA [3],  
SAC [1] 
3.043 
All Treated 
Programming 
Note 
Summary of Worst Post-Baseline Corneal Events 
(GSK Scale) (Arm A – GSK2857916 + Len/Dex (Rd)) 
See Section 15.13 for mock 
 
IA [2], SAC [1] 
3.044 
All Treated 
Programming 
Note 
Summary of Worst Post-Baseline Corneal Events 
(GSK Scale) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
SAC [1] 
3.045 
All Treated 
Mock-up 
SAFE_T3 
Shift in Grade of Corneal Events (Overall GSK Scale) 
from Baseline to Week 13 (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
See Section 15.13 for mock 
 
IA [2] 
3.046 
All Treated 
Mock-up 
SAFE_T3 
Shift in Grade of Corneal Events (Overall GSK Scale) 
from Baseline to Week 10 (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
See Section 15.13 for mock 
 
IA [3] 
3.047 
All Treated 
Mock-up 
SAFE_T3 
Shift in Grade of Corneal Events (Overall GSK Scale) 
from Baseline to End of Treatment (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
See Section 15.13 for mock 
 
SAC [1] 
3.048 
All Treated 
Mock-up 
SAFE_T3 
Shift in Grade of Corneal Events (Overall GSK Scale) 
from Baseline to End of Treatment (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
See Section 15.13 for mock 
 
SAC [1] 


 
CONFIDENTIAL 
 
 
 
207497 
 
141 
 
Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.049 
All Treated  
AE17A 
Summary of Exposure Adjusted Incidence Rates of 
Grade 3+ Corneal Events (Overall GSK Scale) (Arm A 
– GSK2857916 + Len/Dex (Rd)) 
Only provide exposure adjusted rates for 
grade 3+ corneal events (using definition in 
Section 8.2.2). 
 
No subgroups needed. Only ANY EVENT. 
Delete the “Total PY” column.  
Only keep footnote [1] 
See Section 15.13 for mock 
Only create for IA2 if time allows 
 
IA [2], SAC [1] 
3.050 
All Treated  
AE17A 
Summary of Exposure Adjusted Incidence Rates of 
Grade 3+ Corneal Events (Overall GSK Scale) (Arm B 
– GSK2857916 + Bor/Dex (Vd)) 
Only provide exposure adjusted rates for 
grade 3+ corneal events (using definition in 
Section 8.2.2). 
 
No subgroups needed. Only ANY EVENT. 
Delete the “Total PY” column.  
Only keep footnote [1] 
See Section 15.13 for mock 
IA [3], SAC [1] 
3.051 
All Treated 
ESI1 
Summary of Characteristics of Corneal Events 
(CTCAE) (Arm A – GSK2857916 + Len/Dex (Rd)) 
See mock in Section 15.13 with categories 
and footnotes to include. 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
IA [2], SAC [1] 
3.052 
All Treated 
ESI1 
Summary of Characteristics of Corneal Events 
(CTCAE) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
SAC [1] 


 
CONFIDENTIAL 
 
 
 
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142 
 
Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.053 
All Treated 
AE13 
Corneal Event Overview (CTCAE) (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
- See mock in Section 15.13 with categories 
and footnotes to include. In shell, for rows 
that state “Lenalidomide/Bortezomib” – use 
“Lenalidomide” for Arm A. 
- For all categories use “corneal” AEs and 
“corneal “events” 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
 
Add footnote:  
No dose reduction of GSK2857916 allowed 
for 1.9 mg/kg STRETCH and SINGLE  
SAC [1] 
3.054 
All Treated 
AE13 
Corneal Event Overview (CTCAE) (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
- See mock in Section 15.13 with categories 
and footnotes to include. In shell, for rows 
that state “Lenalidomide/Bortezomib” – use 
“Bortezomib” for Arm B. 
- For all categories use “corneal” AEs and 
“corneal “events” 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
 
Add footnote:  
No dose reduction of GSK2857916 allowed 
for 1.9 mg/kg STRETCH and SINGLE, and 
2.5 mg/kg S/D STRETCH 
 
IA [3], SAC [1] 


 
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No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.055 
All Treated 
OAE07 
Summary of Corneal Events (CTCAE) by Preferred 
Term and Maximum Grade (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
IA [2], SAC [1] 
3.056 
All Treated 
OAE07 
Summary of Corneal Events (CTCAE) by Preferred 
Term and Maximum Grade (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
IA [1], IA [3],  
SAC [1] 
3.057 
All Treated 
AE6 
Summary of Cumulative Incidence of Corneal Events 
(CTCAE) by Preferred Term and Number of Doses 
Received at First Occurrence (Arm A – GSK2857916 
+ Len/Dex (Rd)) 
Only PT. The number of doses received at 
first occurrence will be <= 1, <= 2, <= 4, <= 
6, <= 8, <= 10, and Any 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
IA [2], SAC [1] 
3.058 
All Treated 
AE6 
Summary of Cumulative Incidence of Corneal Events 
(CTCAE) by Preferred Term and Number of Doses 
Received at First Occurrence (Arm B – GSK2857916 
+ Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
SAC [1] 
3.059 
All Treated  
ESI1 
Summary of Characteristics of Keratopathy Events 
(CTCAE) (Arm A – GSK2857916 + Len/Dex (Rd)) 
See mock in Section 15.13 with categories 
and footnotes to include. 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
IA [2], SAC [1] 
3.060 
All Treated  
ESI1 
Summary of Characteristics of Keratopathy Events 
(CTCAE) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
 
Also, add a footnote:  
For IDs 2, 3, 6 (Arm B 2.5 mg/kg SINGLE), 
total number of adverse events may be 
overreported due to a site related unfixable 
non-standard logging of ongoing events. 
IA [1], IA [3],  
SAC [1] 


 
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No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.061 
All Treated  
ESI1 
Summary of Characteristics of Blurred Vision Events 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
See mock in Section 15.13 with categories 
and footnotes to include. 
 
Additional Footnote:  
Note: Blurred Vision events as collected in 
the AE eCRF, including MedDRA terms 
based on clinical review. 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
IA [2], SAC [1] 
3.062 
All Treated  
ESI1 
Summary of Characteristics of Blurred Vision Events 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
 
Also, add a footnote:  
For IDs 2, 3, 6, total number of adverse 
events may be overreported due to a site 
related unfixable non-standard logging of 
ongoing events 
 
IA [3], SAC [1] 
3.063 
All Treated 
ESI1 
Summary of Characteristics of Thrombocytopenia 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
See mock in Section 15.13 with categories 
and footnotes to include. 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
 
Add an additional footnote:  
Note: Thrombocytopenia events as collected 
in the AE eCRF, including MedDRA terms 
based on clinical review. 
IA [2], SAC [1] 
3.064 
All Treated 
ESI1 
Summary of Characteristics of Thrombocytopenia 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
SAC [1] 


 
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No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.065 
All Treated 
OAE07 
Summary of Thrombocytopenia by Preferred Term 
and Maximum Grade (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
IA [2], SAC [1] 
3.066 
All Treated 
OAE07 
Summary of Thrombocytopenia by Preferred Term 
and Maximum Grade (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
IA [1], IA [3],  
SAC [1] 
3.067 
All Treated 
ESI2b 
Summary of Onset and Duration of the First 
Occurrence of Thrombocytopenia (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Time of onset: 1-28, 29-56, 57-84, >84. 
Duration: 1-28, 29-56, >56. Mean, SD, 
Median, Min, Max 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
 
Footnotes:  
[1] Not Evaluable means the event outcome 
was 'NOT RECOVERED/NOT RESOLVED' 
or 'RECOVERING/RESOLVING' with no end 
date. 
Note: Time of onset assessed only for those 
subjects experiencing Thrombocytopenia. 
Note: Thrombocytopenia events as collected 
in the AE eCRF, including MedDRA terms 
based on clinical review. 
IA [2], SAC [1] 


 
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No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.068 
All Treated 
ESI2b 
Summary of Onset and Duration of the First 
Occurrence of Thrombocytopenia (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Time of onset: 1-21, 22-42, 43-63, >63. 
Duration: 1-21, 22-42, >42. Mean, SD, 
Median, Min, Max 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
IA [1], IA [3],  
SAC [1] 
3.069 
All Treated 
AE6 
Summary of Cumulative Incidence of 
Thrombocytopenia by Preferred Term and Number of 
Doses Received at First Occurrence (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Only PT. The number of doses received at 
first occurrence will be <= 1, <= 2, <= 4, <= 
6, <= 8, <= 10, and Any 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
 
Footnote:  
Note: Thrombocytopenia events as collected 
in the AE eCRF, including MedDRA terms 
based on clinical review. 
SAC [1] 
3.070 
All Treated 
AE6 
Summary of Cumulative Incidence of 
Thrombocytopenia by Preferred Term and Number of 
Doses Received at First Occurrence (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
SAC [1] 


 
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No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.071 
All Treated 
SAFE_T11 
Summary of Thrombocytopenia and Bleeding Event 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
 
Footnotes:  
[1] Lab data where Toxicity=’Platelet count 
decreased’ and Standard Toxicity Grade=3 
or 4. 
[2] On-treatment Bleeding events include: 
Haemorrhage events as collected in the AE 
eCRF, including 
MedDRA terms based on clinical review; as 
well as Thrombocytopenia events as 
collected in the AE 
eCRF with ‘Was there bleeding associated 
with the thrombocytopenia?’=Y, with 
Maximum Grade 2 or above. 
[3] Concomitant events are those from 
statement [1] and statement [2] that occur on 
the same day or 
within +/- 3 days and the event is on-
treatment. 
IA [2], SAC [1] 
3.072 
All Treated 
SAFE_T11 
Summary of Thrombocytopenia and Bleeding Event 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
SAC [1] 


 
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Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.073 
All Treated 
ESI1 
Summary of Characteristics of Infusion-Related 
Reactions (Arm A – GSK2857916 + Len/Dex (Rd)) 
See mock in Section 15.13 with categories 
and footnotes to include. 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
 
Additional Footnote: 
 
Note: IRR events as collected in the AE 
eCRF, including MedDRA terms based on 
clinical review. 
IA [2], SAC [1] 
3.074 
All Treated 
ESI1 
Summary of Characteristics of Infusion-Related 
Reactions (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
SAC [1] 
3.075 
All Treated 
OAE07 
Summary of Infusion-Related Reactions by Preferred 
Term and Maximum Grade (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
IA [2], SAC [1] 
3.076 
All Treated 
OAE07 
Summary of Infusion-Related Reactions by Preferred 
Term and Maximum Grade (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
IA [1], IA [3],  
SAC [1] 
3.077 
All Treated 
ESI1 
Summary of Characteristics of Neutropenia (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
See mock in Section 15.13 with categories 
and footnotes to include. 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
 
Additional Footnote:  
Note: Neutropenia events as collected in the 
AE eCRF, including MedDRA terms based 
on clinical review. 
 
IA [2], SAC [1] 


 
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No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.078 
All Treated 
ESI1 
Summary of Characteristics of Neutropenia (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1],  
SAC [1] 
3.079 
All Treated 
OAE07 
Summary of Neutropenia by Preferred Term and 
Maximum Grade (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
SAC [1] 
3.080 
All Treated 
OAE07 
Summary of Neutropenia by Preferred Term and 
Maximum Grade (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
Use definition of treatment emergent AEs as 
seen in Section 15.2.3 
IA [1],  
SAC [1] 
3.081 
All Treated 
AE6 
Summary of Cumulative Incidence of Neutropenia by 
Preferred Term and Number of Doses Received at 
First Occurrence (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
Only PT. The number of doses received at 
first occurrence will be <= 1, <= 2, <= 4, <= 
6, <= 8, <= 10, and Any 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
SAC [1] 
3.082 
All Treated 
AE6 
Summary of Cumulative Incidence of Neutropenia by 
Preferred Term and Number of Doses Received at 
First Occurrence (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
Same as above 
IA [1],  
SAC [1] 
3.083 
All Treated 
SAFE_T11a 
Summary of Neutropenia and Infection Event (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
SAC [1] 
3.084 
All Treated 
SAFE_T11a 
Summary of Neutropenia and Infection Event (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
IA [1],  
SAC [1] 


 
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Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.085 
All Treated 
ESI1 
Summary of Characteristics of Haematological Toxicity 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
Include summary outcome of AE 
 
*See mock shell in Section 15.13 for 
specifications 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
 
Additional Footnote:  
Note: Haematological Toxicity events, 
identified using MedDRA terms based on 
clinical review. 
IA [2], SAC [1] 
3.086 
All Treated 
ESI1 
Summary of Characteristics of Haematological Toxicity 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
 
Also, add a footnote:  
For IDs 2, 3, 6, total number of adverse 
events may be overreported due to a site 
related unfixable non-standard logging of 
ongoing events. 
IA [1], IA [3],  
SAC [1] 
Deaths 
3.087 
All Treated  
DTH1a 
Summary of Deaths (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
IDSL 
Include Subject Status, Primary Cause of 
Death, and Time to Death from Last Dose 
IA [2], HDL [1], SAC [1] 
3.088 
All Treated  
DTH1a 
Summary of Deaths (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
Same as above 
IA [1], IA [3], HDL [1], 
SAC [1] 
Laboratory: Chemistry  
3.089 
All Treated 
LB1 
Summary of Chemistry Changes from Baseline (Arm A 
– GSK2857916 + Len/Dex (Rd)) 
ICH E3. 
SAC [1] 


 
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No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.090 
All Treated 
LB1 
Summary of Chemistry Changes from Baseline (Arm B 
– GSK2857916 + Bor/Dex (Vd)) 
ICH E3. 
SAC [1] 
3.091 
All Treated  
OLB9B 
Summary of Worst Case Chemistry Grade Changes 
from Baseline Grade (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
 
SAC [1] 
3.092 
All Treated  
OLB9B 
Summary of Worst Case Chemistry Grade Changes 
from Baseline Grade (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
 
SAC [1] 
3.093 
All Treated 
OLB11B 
Summary of Worst Case Chemistry Changes from 
Baseline with Respect to the Normal Range (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
ICH E3 
 
IA [2], SAC [1] 
3.094 
All Treated 
OLB11B 
Summary of Worst Case Chemistry Changes from 
Baseline with Respect to the Normal Range (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
 
IA [1], IA [3],  
SAC [1] 
Laboratory: Haematology 
3.095 
All Treated 
LB1  
Summary of Haematology Changes from Baseline 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
ICH E3 
SAC [1] 
3.096 
All Treated 
LB1  
Summary of Haematology Changes from Baseline 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
SAC [1] 
3.097 
All Treated  
OLB9B 
Summary of Worst Case Haematology Grade 
Changes from Baseline Grade (Arm A – GSK2857916 
+ Len/Dex (Rd)) 
 
SAC [1] 
3.098 
All Treated  
OLB9B 
Summary of Worst Case Haematology Grade 
Changes from Baseline Grade (Arm B – GSK2857916 
+ Bor/Dex (Vd)) 
 
SAC [1] 


 
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No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.099 
All Treated 
OLB11B 
Summary of Worst Case Haematology Changes from 
Baseline with Respect to the Normal Range (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
ICH E3 
 
 
IA [2], SAC [1] 
3.100 
All Treated 
OLB11B 
Summary of Worst Case Haematology Changes from 
Baseline with Respect to the Normal Range (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
 
 
IA [1], IA [3],  
SAC [1] 
Laboratory: Urinalysis 
3.101 
All Treated 
LB1 
Summary of Urine Concentration Changes from 
Baseline (Arm A – GSK2857916 + Len/Dex (Rd)) 
ICH E3 
SAC [1] 
3.102 
All Treated 
LB1 
Summary of Urine Concentration Changes from 
Baseline (Arm B – GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
SAC [1] 
3.103 
All Treated 
UR1 
Summary of Worst Case Urinalysis Results (Discrete 
or Character Values) Post-Baseline Relative to 
Baseline (Arm A – GSK2857916 + Len/Dex (Rd)) 
ICH E3 
SAC [1] 
3.104 
All Treated 
UR1 
Summary of Worst Case Urinalysis Results (Discrete 
or Character Values) Post-Baseline Relative to 
Baseline (Arm B – GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
SAC [1] 
Laboratory: Hepatobiliary (Liver) 
3.105 
All Treated 
LIVER1 
Summary of Liver Monitoring/Stopping Event 
Reporting (Arm A – GSK2857916 + Len/Dex (Rd)) 
IDSL 
SAC [1] 
3.106 
All Treated 
LIVER1 
Summary of Liver Monitoring/Stopping Event 
Reporting (Arm B – GSK2857916 + Bor/Dex (Vd)) 
IDSL 
SAC [1] 
3.107 
All Treated 
LIVER10 
Summary of Hepatobiliary Laboratory Abnormalities 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
IDSL 
SAC [1] 


 
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No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.108 
All Treated 
LIVER10 
Summary of Hepatobiliary Laboratory Abnormalities 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
IDSL 
SAC [1] 
ECG 
3.109 
All Treated 
OECG2B 
Summary of Worst-case Amount of Increase from 
Baseline Value in Fridericia’s QTc (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
IDSL 
 
Use same definition of “worst-case” as study 
159 in Table 3.0392 (primary_02). Add 
categories as seen in Section 8.8 
 
No “Planned Time” column is necessary. 
 
Add footnote to the “category” column:  
[2] Counts within categories may not add up 
to counts within ‘n’. 
IA [2], SAC [1] 
3.110 
All Treated 
OECG2B 
Summary of Worst-case Amount of Increase from 
Baseline Value in Fridericia’s QTc (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3], 
SAC [1] 
Vital Signs 
3.111 
All Treated 
VS1 
Summary of Change from Baseline in Vital Signs (Arm 
A – GSK2857916 + Len/Dex (Rd)) 
ICH E3 
Add footnote:  
Note: ‘BASELINE’ visit displays actual Vital 
Signs at Baseline. Any post-baseline visit 
displays change from baseline in Vital 
Signs.” 
SAC [1] 


 
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Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.112 
All Treated 
VS1 
Summary of Change from Baseline in Vital Signs (Arm 
B – GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
Add footnote:  
Note: ‘BASELINE’ visit displays actual Vital 
Signs at Baseline. Any post-baseline visit 
displays change from baseline in Vital 
Signs.” 
SAC [1] 
Dose Limiting Toxicity (DLT) 
3.113 
All Treated 
AE19 
Summary of Dose-Limiting Toxicities during the 
Determinative Period (Arm A – Part 1) 
 
ICH E3 
SAC [1] 
3.114 
All Treated 
DL1 
Summary of Dose-Limiting Toxicities during the 
Determinative Period (Arm B – Part 1) 
 
ICH E3 
IA [1], IA [3], 
SAC [1] 
Ocular findings for General study (Baseline to Last follow-up) 
3.115 
All Treated 
Programming 
note 
Summary of Best Corrected Visual Acuity Test (BCVA) 
Scores (logMAR score) (Arm A – GSK2857916 + 
Len/Dex (Rd))  
Use Table 3.0501 from BMA117159 
(primary_01) study as template. Following 
“worst change from baseline’, add summary 
for ‘Most frequent Visual Acuity Change, and 
pick the worst category if there is tie. Under 
column ‘Eye’, in addition to Right/Left add 
‘Better’ (better of two eye). Definition of 3 
categories of change are same as in 
BMA117159 (primary_01). See Section 
15.13 for mock and footnotes.  
IA [2], SAC [1] 
3.116 
All Treated 
Programming 
note 
Summary of Best Corrected Visual Acuity Test (BCVA) 
Scores (logMAR score) (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Same as above 
IA [1], Post-Interim [1], 
IA [3], 
SAC [1] 


 
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Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.117 
All Treated 
Programming 
note 
Summary of Best Corrected Visual Acuity Test (BCVA) 
Scores (logMAR score) due to Corneal Event (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
[1] Use Table 3.0501 from BMA117159 
(primary_01) study as template. Following 
“worst change from baseline’, add summary 
for ‘Most frequent Visual Acuity Change, and 
pick the worst category if there is tie. Under 
column ‘Eye’, in addition to Right/Left add 
‘Better’ (better of two eye). Definition of 3 
categories of change are same as in 
BMA117159 (primary_01). Only include 
those visits with BCVA due to corneal event 
flag=’Y’. See Section 15.13 for mock. 
IA [2], SAC [1] 
3.118 
All Treated 
Programming 
note 
Summary of Best Corrected Visual Acuity Test (BCVA) 
Scores (logMAR score) due to Corneal Event (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3], 
SAC [1] 
3.119 
All Treated 
Mock-up 
SAFE_T8 
Number (%) of Subjects with a Decline in Best 
Corrected Visual acuity (BCVA) to LP or NLP due to a 
Corneal Event Anytime Post-Baseline (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Eye (R/L) and subject (either eye) 
 
Add footnote:  
’n’ denotes subjects who have any post-
Baseline Best Corrected Visual acuity 
(BCVA) score, where the Visual Acuity is due 
to corneal findings. Categories displayed are 
only counting where ’Light Perception’ or ’No 
Light Perception’ was selected on the Non-
Snellen Acuity item on the Visual Acuity 
(Best Corrected) eCRF, therefore may not 
add up to ’n’. 
IA [2], SAC [1] 
3.120 
All Treated 
Mock-up 
SAFE_T8 
Number (%) of Subjects with a Decline in Best 
Corrected Visual acuity (BCVA) to LP or NLP due to a 
Corneal Event Anytime Post-Baseline (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], Post-Interim [1], 
IA [3], 
SAC [1] 


 
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No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.121 
All Treated 
BCVACHANGE 
Summary of Worst Post-Baseline Best Corrected 
Visual Acuity (BCVA) Change in Snellen Results (Arm 
A – GSK2857916 + Len/Dex (Rd)) 
See mock figure in Section 15.13 
 
Groups for “Number of Lines Change from 
Baseline” (Better Eye, Worse Eye):  
Improved BCVA 
<= 2 Lines decline 
>= 3 Lines decline 
 
Add footnotes as seen in the mock figure.  
IA [2], HDL [1], SAC [1] 
3.122 
All Treated 
BCVACHANGE 
Summary of Worst Post-Baseline Best Corrected 
Visual Acuity (BCVA) Change in Snellen Results (Arm 
B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [3], HDL [1], SAC [1] 
3.123 
All Treated 
BCVACHANGE 
Summary of Worst Post-Baseline Best Corrected 
Visual Acuity (BCVA) due to Corneal Event Change in 
Snellen Results (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
See mock figure in Section 15.13 
 
Groups for “Number of Lines Change from 
Baseline” (Better Eye, Worse Eye):  
Improved BCVA 
<= 2 Lines decline 
>= 3 Lines decline 
 
Add footnotes as seen in the mock figure.  
IA [3], SAC [1] 


 
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No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.124 
All Treated 
BCVACHANGE 
Summary of Worst Post-Baseline Best Corrected 
Visual Acuity (BCVA) due to Corneal Event Change in 
Snellen Results (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
See mock figure in Section 15.13 
 
Groups for “Number of Lines Change from 
Baseline” (Better Eye, Worse Eye):  
Improved BCVA 
<= 2 Lines decline 
>= 3 Lines decline 
 
Add footnotes as seen in the mock figure.  
IA [3], SAC [1] 
3.125 
All Treated 
Mock-up 
SAFE_T9 
Shift in Corneal Epithelium Findings from Baseline to 
Worst Post-Baseline (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
By eye (R/L) and subject (worse eye). See 
Section 8.5 Ocular findings from ophthalmic 
exam for details. 
IA [2], SAC [1] 
3.126 
All Treated 
Mock-up 
SAFE_T9 
Shift in Corneal Epithelium Findings from Baseline to 
Worst Post-Baseline (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
By eye (R/L) and subject (worse eye). See 
Section 8.5 Ocular findings from ophthalmic 
exam for details. 
IA [1], Post-Interim [1], 
IA [3], 
SAC [1] 
3.127 
All Treated 
Mock-up 
SAFE_T14 
Summary of Findings for Punctate Keratopathy (Arm A 
– GSK2857916 + Len/Dex (Rd)) 
By eye (R/L) and subject (worse eye). See 
Section 8.5 Ocular findings from ophthalmic 
exam for details. 
 
Add footnote:  
Note: n reflects the number of subjects with 
an eye with Punctate Keratopathy worse 
than Baseline at any Post-Baseline 
Ocular Exam. 
IA [2], SAC [1] 
3.128 
All Treated 
Mock-up 
SAFE_T14 
Summary of Findings for Punctate Keratopathy (Arm B 
– GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], Post-Interim [1], 
IA [3], SAC [1] 


 
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Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
Anti-Drug Antibody 
3.129 
All Treated 
IMM1 
Summary of Anti-GSK2857916 Antibody Results by 
Planned Time and Treatment (Arm A – GSK2857916 
+ Len/Dex (Rd)) 
Use Table 3.0940 from Study 207495 
(primary_01) study as template 
 
Table will be produced by each visit and 
present data as shown in the mock-shell.  
 
Do not include Conclusive and Inconclusive 
rows. And only keep Titer data if there are 
positive results. 
AAC [1] 
3.130 
All Treated 
IMM1 
Summary of Anti-GSK2857916 Antibody Results by 
Planned Time and Treatment (Arm B – GSK2857916 
+ Bor/Dex (Vd)) 
Use Table 3.0940 from Study 207495 
(primary_01) study as template 
 
Table will be produced by each visit and 
present data as shown in the mock-shell.  
 
Do not include Conclusive and Inconclusive 
rows. And only keep Titer data if there are 
positive results. 
AAC [1] 
3.131 
All Treated 
IMM2 
Summary of Neutralizing Anti-GSK2857916 Antibody 
Results by Planned Time and Treatment (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Use Table 3.0950 from Study 207495 
(primary_01) study as template 
 
Table will be produced by each visit and 
present data as shown in the mock-shell. 
AAC [1] 
3.132 
All Treated 
IMM2 
Summary of Neutralizing Anti-GSK2857916 Antibody 
Results by Planned Time and Treatment (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Use Table 3.0950 from Study 207495 
(primary_01) study as template 
 
Table will be produced by each visit and 
present data as shown in the mock-shell. 
AAC [1] 


 
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Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.133 
All Treated 
IMM4 
GSK2857916 Immunogenicity Incidence and 
Summary (Arm A – GSK2857916 + Len/Dex (Rd)) 
Use Table 3.0955 from Study 207495 
(primary_01) study as template 
 
Produce Transient and Persistent Rows if 
possible. Use definitions in the 
Immunogenicity Display Standard Text 
Document. 
AAC [1] 
3.134 
All Treated 
IMM4 
GSK2857916 Immunogenicity Incidence and 
Summary  (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Use Table 3.0955 from Study 207495 
(primary_01) study as template 
 
Produce Transient and Persistent Rows if 
possible. Use definitions in the 
Immunogenicity Display Standard Text 
Document. 
AAC [1] 


 
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No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
Additional Tables 
3.137 
All Treated 
AE13 
Adverse Event Overview for Non-Corneal Events (Arm 
A – GSK2857916 + Len/Dex (Rd)) 
This table will be produced for all AEs that 
are not categorized as corneal events.  
 
See mock in Section 15.3 with categories 
and footnotes to include. In shell, for rows 
that state “Lenalidomide/Bortezomib” – use 
“Lenalidomide” for Arm A. 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
 
Add footnote:  
No dose reduction of GSK2857916 allowed 
for 1.9 mg/kg STRETCH and SINGLE 
SAC [1] 


 
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Safety: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable [Priority] 
3.138 
All Treated 
AE13 
Adverse Event Overview for Non-Corneal Events (Arm 
B – GSK2857916 + Bor/Dex (Vd)) 
This table will be produced for all AEs that 
are not categorized as corneal events.  
 
See mock in Section 15.13with categories 
and footnotes to include. In shell, for rows 
that state “Lenalidomide/Bortezomib” – use 
“Bortezomib” for Arm B. 
 
Use definition of on-treatment AEs as seen 
in Section 15.2.3 
 
Add footnote:  
No dose reduction of GSK2857916 allowed 
for 1.9 mg/kg STRETCH and SINGLE, and 
2.5 mg/kg S/D STRETCH 
SAC [1] 
 
15.12.7. 
Safety Figures 
Safety: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 


 
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No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Profile Plot 
3.135 
All Treated 
 
Programming 
Note 
Profile Plot for Subjects (Arm A – GSK2857916 + Len/Dex (Rd)) 
See similar Figure 3.0031 from BCMA 
Study 205678 (primary_01). Make the 
max x-axis value equal to the max study 
treatment duration (days) for all subjects.  
 
Create for IA [2] if time allows 
IA [2], SAC [1] 
3.136 
All Treated 
 
Programming 
Note 
Profile Plot for Subjects (Arm B – GSK2857916 + Bor/Dex (Vd)) 
See similar Figure 3.0031 from BCMA 
Study 205678 (primary_01). Make the 
max x-axis value equal to the max study 
treatment duration (days) for all subjects.  
 
Create for IA [3] if time allows 
IA [1], IA [3], 
SAC [1] 
 


 
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15.12.8. 
Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
PK Parameter 
4.001 
PK GSK2857916 
PK06 
Summary of Derived GSK2857916 (ADC) PK Parameters (Arm 
A – GSK2857916 + Len/Dex (Rd)) 
PK06 with both transformed and 
untransformed values. 
 
Only display means, median, SD, 
and CVb if n ≥ 3, and only display 
visits up to Week 13 Day 8 for 
CEOI/CTROUGH 
 
Any concentration pk parameters 
for ADC/Tab will be reported at 
ug/mL and for cys-mcMMAF in 
ng/mL. 
 
For Ctrough, add the following 
footnote: “Ctrough for a dosing 
profile, represents the 
concentration prior to the next 
dose.” 
 
For tlast, add the following 
footnote: “The dose reference for 
Tlast is the time since most recent 
dose” 
AAC [1] 
4.002 
PK GSK2857916 
PK06 
Summary of Derived GSK2857916 (ADC) PK Parameters (Arm 
B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3], 
AAC [1] 


 
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Pharmacokinetic: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.003 
PK GSK2857916 
PK06 
Summary of Derived GSK2857916 (Total Antibody) PK 
Parameters (Arm A – GSK2857916 + Len/Dex (Rd)) 
Same as above 
AAC [1] 
4.004 
PK GSK2857916 
PK06 
Summary of Derived GSK2857916 (Total Antibody) PK 
Parameters (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
AAC [1] 
4.005 
PK GSK2857916 
PK06 
Summary of Derived cys-mcMMAF PK Parameter (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Same as above 
AAC [1] 
4.006 
PK GSK2857916 
PK06 
Summary of Derived cys-mcMMAF PK Parameter (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
AAC [1] 
4.007 
PK Lenalidomide 
25mg 
PK06 
Summary of Derived Lenalidomide 25mg PK Parameter (Arm A 
– GSK2857916 + Len/Dex (Rd)) 
Same as above 
IA [2], AAC [1] 
4.008 
PK Lenalidomide 
10mg  
PK06 
Summary of Derived Lenalidomide 10mg PK Parameter (Arm A 
– GSK2857916 + Len/Dex (Rd)) 
Same as above 
IA [2], AAC [1] 
4.009 
PK Bortezomib 
PK06 
Summary of Derived Bortezomib PK Parameter (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Same as above.  
Also, summarize by route (IV vs. 
SC) 
IA [3], AAC [1] 
4.010 
PK GSK2857916 
PK13 
Listing of Derived GSK2857916 (ADC) PK Parameters 
(Untransformed) (Arm A – GSK2857916 + Len/Dex (Rd)) 
Produce Listing by Treatment 
 
Add a column for “Actual Dose” 
and “Dose Number” to the listing. 
“Dose Number” column only 
applicable for ADC, Tab, cys-
mcMMAF. 
AAC [1] 
4.011 
PK GSK2857916 
PK13 
Listing of Derived GSK2857916 (ADC) PK Parameters 
(Untransformed) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
AAC [1] 


 
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Pharmacokinetic: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.012 
PK GSK2857916 
PK13 
Listing of Derived GSK2857916 (Total Antibody) PK Parameters 
(Untransformed) (Arm A – GSK2857916 + Len/Dex (Rd)) 
Same as above 
AAC [1] 
4.013 
PK GSK2857916 
PK13 
Listing of Derived GSK2857916 (Total Antibody) PK Parameters 
(Untransformed) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
AAC [1] 
4.014 
PK GSK2857916 
PK13 
Listing of Derived cys-mcMMAF PK Parameters 
(Untransformed) (Arm A – GSK2857916 + Len/Dex (Rd)) 
Same as above 
AAC [1] 
4.015 
PK GSK2857916 
PK13 
Listing of Derived cys-mcMMAF PK Parameters 
(Untransformed) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3],  
AAC [1] 
4.016 
PK Lenalidomide 
25mg 
PK13 
Listing of Derived Lenalidomide 25mg PK Parameters 
(Untransformed) (Arm A – GSK2857916 + Len/Dex (Rd)) 
Produce Listing by Treatment 
Dose Number column not 
applicable 
 
IA [2], AAC [1] 
4.017 
PK Lenalidomide 
10mg 
PK13 
Listing of Derived Lenalidomide 10mg PK Parameters 
(Untransformed) (Arm A – GSK2857916 + Len/Dex (Rd)) 
Produce Listing by Treatment 
Dose Number column not 
applicable 
 
IA [2], AAC [1] 
4.018 
PK Bortezomib 
PK13 
Listing of Derived Bortezomib PK Parameters (Untransformed) 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
 
Produce Listing by Treatment 
Also, add in column for Route (IV 
vs. SC 
Dose Number column not 
applicable 
IA [3], AAC [1] 
Concentration 


 
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Pharmacokinetic: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.019 
PK GSK2857916 
PK01 
Summary of Plasma GSK2857916 (ADC) PK Concentration-
Time Data (Arm A – GSK2857916 + Len/Dex (Rd)) 
By cohort 
 
Only display mean, median, and 
SD if n ≥ 3 
AAC [1] 
4.020 
PK GSK2857916 
PK01 
Summary of Plasma GSK2857916 (ADC) PK Concentration-
Time Data (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [3], AAC [1] 
4.021 
PK GSK2857916 
PK01 
Summary of Plasma GSK2857916 (Total Antibody) PK 
Concentration-Time Data (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
Same as above 
AAC [1] 
4.022 
PK GSK2857916 
PK01 
Summary of Plasma GSK2857916 (Total Antibody) PK 
Concentration-Time Data (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
Same as above 
IA [3], AAC [1] 
4.023 
PK GSK2857916 
PK01 
Summary of Plasma cys-mcMMAF PK Concentration-Time Data 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
Same as above 
AAC [1] 
4.024 
PK GSK2857916 
PK01 
Summary of Plasma cys-mcMMAF PK Concentration-Time Data 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
IA [3], AAC [1] 
4.025 
PK Lenalidomide 
25mg 
PK01 
Summary of Lenalidomide 25mg PK Concentration-Time Data 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
Same as above 
AAC [1] 
4.026 
PK Lenalidomide 
10mg 
PK01 
Summary of Lenalidomide 10mg PK Concentration-Time Data 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
Same as above 
AAC [1] 
4.027 
PK Bortezomib 
PK01 
Summary of Bortezomib PK Concentration-Time Data (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Same as above 
Also, summarize by route (IV vs. 
SC) 
IA [3], AAC [1] 


 
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15.12.9. 
Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Concentration 
4.028 
PK 
GSK2857916 
PK16 
Individual Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Arm A – GSK2857916 + Len/Dex (Rd)) 
In second title, add “Treatment” to 
include cohort for each subject: 
“Treatment = x.x mg/kg, Subject = 
xxxxxx” 
AAC [1] 
4.029 
PK 
GSK2857916 
PK16 
Individual Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
In second title, add “Treatment” to 
include cohort for each subject: 
“Treatment = x.x mg/kg, Subject = 
xxxxxx” 
IA [1], IA [3],  
AAC [1] 
4.030 
PK 
GSK2857916 
PK16 
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) (Arm A – GSK2857916 + Len/Dex (Rd)) 
In second title, add “Treatment” to 
include cohort for each subject: 
“Treatment = x.x mg/kg, Subject = 
xxxxxx” 
AAC [1] 
4.031 
PK 
GSK2857916 
PK16 
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
In second title, add “Treatment” to 
include cohort for each subject: 
“Treatment = x.x mg/kg, Subject = 
xxxxxx” 
IA [1], IA [3],  
AAC [1] 
4.032 
PK 
GSK2857916 
PK16 
Individual Plasma Total Antibody Concentration-Time Plots 
(Linear and Semi-Log) (Arm A – GSK2857916 + Len/Dex (Rd)) 
In second title, add “Treatment” to 
include cohort for each subject: 
“Treatment = x.x mg/kg, Subject = 
xxxxxx” 
AAC [1] 
4.033 
PK 
GSK2857916 
PK16 
Individual Plasma Total Antibody Concentration-Time Plots 
(Linear and Semi-Log) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
In second title, add “Treatment” to 
include cohort for each subject: 
“Treatment = x.x mg/kg, Subject = 
xxxxxx” 
IA [3], AAC [1] 


 
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Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.034 
PK Lenalidomide 
25mg 
PK16 
Individual Plasma Lenalidomide 25mg Concentration-Time Plots 
(Linear and Semi-Log) (Arm A – GSK2857916 + Len/Dex (Rd)) 
In second title, add “Treatment” to 
include cohort for each subject: 
“Treatment = x.x mg/kg, Subject = 
xxxxxx” 
IA [2], AAC [1] 
4.035 
PK Lenalidomide 
10mg 
PK16 
Individual Plasma Lenalidomide 10mg Concentration-Time Plots 
(Linear and Semi-Log) (Arm A – GSK2857916 + Len/Dex (Rd)) 
In second title, add “Treatment” to 
include cohort for each subject: 
“Treatment = x.x mg/kg, Subject = 
xxxxxx” 
IA [2], AAC [1] 
4.036 
PK Bortezomib 
PK16 
Individual Plasma Bortezomib Concentration-Time Plots (Linear 
and Semi-Log) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
In second title, add “Treatment” to 
include cohort for each subject: 
“Treatment = x.x mg/kg, Subject = 
xxxxxx”, also add route of 
administration (IV or SC) 
IA [3], AAC [1] 
4.037 
PK 
GSK2857916 
PK17 
Mean Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Arm A – GSK2857916 + Len/Dex (Rd)) 
Overlay mean lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
AAC [1] 
4.038 
PK 
GSK2857916 
PK17 
Mean Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Overlay mean lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
IA [1],  
AAC [1] 
4.039 
PK 
GSK2857916 
PK17 
Mean Plasma GSK2857916 (cys-mcMMAF) Concentration-Time 
Plots (Linear and Semi-Log) (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
Overlay mean lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
AAC [1] 


 
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Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.040 
PK 
GSK2857916 
PK17 
Mean Plasma GSK2857916 (cys-mcMMAF) Concentration-Time 
Plots (Linear and Semi-Log) (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
Overlay mean lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
IA [1],  
AAC [1] 
4.041 
PK 
GSK2857916 
PK17 
Mean Plasma GSK2857916 (Total Antibody) Concentration-
Time Plots (Linear and Semi-Log) (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
Overlay mean lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
AAC [1] 
4.042 
PK 
GSK2857916 
PK17 
Mean Plasma GSK2857916 (Total Antibody) Concentration-
Time Plots (Linear and Semi-Log) (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Overlay mean lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
AAC [1] 
4.043 
PK 
GSK2857916 
PK18 
Median Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Arm A – GSK2857916 + Len/Dex (Rd)) 
Overlay median lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
AAC [1] 
4.044 
PK 
GSK2857916 
PK18 
Median Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Overlay median lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
IA [1], IA [3],  
AAC [1] 
4.045 
PK 
GSK2857916 
PK18 
Median Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
Overlay median lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
AAC [1] 
4.046 
PK 
GSK2857916 
PK18 
Median Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log) (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Overlay median lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
IA [1], IA [3] 
AAC [1] 


 
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Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.047 
PK 
GSK2857916 
PK18 
Median Plasma GSK2857916 (Total Antibody) Concentration-
Time Plots (Linear and Semi-Log) (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
Overlay median lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
AAC [1] 
4.048 
PK 
GSK2857916 
PK18 
Median Plasma GSK2857916 (Total Antibody) Concentration-
Time Plots (Linear and Semi-Log) (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Overlay median lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
IA [3], AAC [1] 
4.049 
PK Lenalidomide 
25mg 
PK18 
Mean Plasma Lenalidomide 25mg Concentration-Time Plots 
(Linear and Semi-Log) (Arm A – GSK2857916 + Len/Dex (Rd)) 
Overlay mean lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
IA [2], AAC [1] 
4.050 
PK Lenalidomide 
10mg 
PK18 
Mean Plasma Lenalidomide 10mg Concentration-Time Plots 
(Linear and Semi-Log) (Arm A – GSK2857916 + Len/Dex (Rd)) 
Overlay mean lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
IA [2], AAC [1] 
4.051 
PK Lenalidomide 
25mg 
PK18 
Median Plasma Lenalidomide 25mg Concentration-Time Plots 
(Linear and Semi-Log) (Arm A – GSK2857916 + Len/Dex (Rd)) 
Overlay mean lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
IA [2], AAC [1] 
4.052 
PK Lenalidomide 
10mg 
PK18 
Median Plasma Lenalidomide 10mg Concentration-Time Plots 
(Linear and Semi-Log) (Arm A – GSK2857916 + Len/Dex (Rd)) 
Overlay mean lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
IA [2], AAC [1] 


 
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Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.053 
PK Bortezomib 
PK17 
Mean Plasma Bortezomib Concentration-Time Plots (Linear and 
Semi-Log) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Overlay mean lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
Add footnotes: 
Note: IV=Intravenous, 
SC=Subcutaneous. 
Note: LLQ= 0.1 ng/mL. 
Note: The initial bioanalytical method 
had a LLQ of 0.5 ng/mL. This method 
was updated with a LLQ of 0.1 
ng/mL. 
Samples with <LLQ concentration 
with the initial method were re-
analyzed with the updated method. 
Note: Treatment Groups with N=2 or 
less are not presented. 
IA [3], AAC [1] 


 
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172 
 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.054 
PK Bortezomib 
PK18 
Median Plasma Bortezomib Concentration-Time Plots (Linear 
and Semi-Log) (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Overlay median lines for all doses on 
the same plot 
Only display mean line for treatment 
Groups with N≥3 
Add footnotes: 
Note: IV=Intravenous, 
SC=Subcutaneous. 
Note: LLQ= 0.1 ng/mL. 
Note: The initial bioanalytical method 
had a LLQ of 0.5 ng/mL. This method 
was updated with a LLQ of 0.1 
ng/mL. 
Samples with <LLQ concentration 
with the initial method were re-
analyzed with the updated method. 
Note: Treatment Groups with N=2 or 
less are not presented. 
IA [3], AAC [1] 
Cmax Plots 
4.055 
PK 
GSK2857916 
Mock-up 
PK_1 
Individual and Mean Cmax by Dose/Schedule and Day for Cycle 
1 – ADC (Arm A – GSK2857916 + Len/Dex (Rd)) 
See mock figure in Section 15.13 
AAC [1] 
4.056 
PK 
GSK2857916 
Mock-up 
PK_1 
Individual and Mean Cmax by Dose/Schedule and Day for Cycle 
1 – ADC (Arm B – GSK2857916 + Bor/Dex (Vd)) 
See mock figure in Section 15.13 
IA [1], IA [3],  
AAC [1] 
4.057 
PK 
GSK2857916 
Mock-up 
PK_1 
Individual and Mean Cmax by Dose/Schedule and Day for Cycle 
1 – cys-mcMMAF (Arm A – GSK2857916 + Len/Dex (Rd)) 
See mock figure in Section 15.13 
AAC [1] 
4.058 
PK 
GSK2857916 
Mock-up 
PK_1 
Individual and Mean Cmax by Dose/Schedule and Day for Cycle 
1 – cys-mcMMAF (Arm B – GSK2857916 + Bor/Dex (Vd)) 
See mock figure in Section 15.13 
IA [1], IA [3],  
AAC [1] 


 
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Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.059 
PK 
GSK2857916 
Mock-up 
PK_1 
Individual and Mean Cmax by Dose/Schedule and Day for Cycle 
1 – Total Antibody (Arm A – GSK2857916 + Len/Dex (Rd)) 
See mock figure in Section 15.13 
AAC [1] 
4.060 
PK 
GSK2857916 
Mock-up 
PK_1 
Individual and Mean Cmax by Dose/Schedule and Day for Cycle 
1 – Total Antibody (Arm B – GSK2857916 + Bor/Dex (Vd)) 
See mock figure in Section 15.13 
IA [3], AAC [1] 
 
15.12.10. Biomarker Tables 
Biomarker: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
CCI


 
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Biomarker: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
 
 
15.12.11. Biomarker Figures 
Biomarker: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
CCI


 
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Biomarker: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
 
CCI


 
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15.12.12. Patient Reported Outcomes Tables 
Patient Reported Outcomes: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
PRO-CTCAE 
6.001 
All Treated 
PRO_MAX 
Summary of Maximum Post-Baseline PRO-CTCAE Score (Arm A 
– GSK2857916 + Len/Dex (Rd)) 
Summarize by: dose level. Refer to 
mid205678 (primary_01) Table 8.0090 
for guidance. For each selected item 
from PRO-CTCAE library: create 
summary table for maximum post-
baseline PRO-CTCAE score for each of 
3 attributes (frequency, severity and/or 
interference). Presence/Absence will 
only be listed. 
[1] 
6.002 
All Treated 
PRO_MAX 
Summary of Maximum Post-Baseline PRO-CTCAE Score (Arm B 
– GSK2857916 + Bor/Dex (Vd)) 
Summarize by: dose level. Refer to 
mid205678 (primary_01) Table 8.0090 
for guidance. For each selected item 
from PRO-CTCAE library: create 
summary table for maximum post-
baseline PRO-CTCAE score for each of 
3 attributes (frequency, severity and/or 
interference). Presence/Absence will 
only be listed. 
AAC [1] 
OSDI 
6.003 
All Treated 
OSDI_CHG_TOT Summary of Change in OSDI Total Scores from Baseline (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Summarize by: dose level. Refer to 
mid205678 (primary_01) Table 8.00130 
for guidance. 
 
AAC [1] 
6.004 
All Treated 
OSDI_CHG_TOT Summary of Change in OSDI Total Scores from Baseline (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Summarize by: dose level. Refer to 
mid205678 (primary_01) Table 8.00130 
for guidance. 
 
AAC [1] 


 
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Patient Reported Outcomes: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.005 
All Treated 
OSDI_CHG_SUB Summary of Change in OSDI Subscale Scores from Baseline (Arm 
A – GSK2857916 + Len/Dex (Rd)) 
Summarize by: dose level. Refer to 
mid205678 (primary_01) Table 8.00130 
for guidance. 
Descriptive stats + frequencies of 
worsening >=12.5 (VRF). Refer to 
mid207503 (internal_02) Table 5.11 for 
guidance on VRF 12.5 worsening.  
AAC [1] 
6.006 
All Treated 
OSDI_CHG_SUB Summary of Change in OSDI Subscale Scores from Baseline (Arm 
B – GSK2857916 + Bor/Dex (Vd)) 
Summarize by: dose level. Refer to 
mid205678 (primary_01) Table 8.00130 
for guidance. 
Descriptive stats + frequencies of 
worsening >=12.5 (VRF). Refer to 
mid207503 (internal_02) Table 5.11 for 
guidance on VRF 12.5 worsening. 
AAC [1] 


 
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Patient Reported Outcomes: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.007 
All Treated 
OSDI_DET 
Summary of Patients with a 12.5 Point or Greater Deterioration 
from Baseline in the Visual Related Function Subscale Score (Arm 
A – GSK2857916 + Len/Dex (Rd)) 
Summarize by: dose level. Refer to 
mid205207 (primary_03) Table 
6.0003for guidance. Include the 
following footnotes: 
(1) Improvement is defined as a 
decrease from the worst subscale score 
of at least 12.5 points. 
(2) Time to 12.5 point deterioration 
assessed only for those subjects 
experiencing a first worsening of at least 
one 12.5 unit as compared to the 
baseline score with complete onset 
date. 
(3) Duration is defined as time from the 
onset of first worsening of at least one 
12.5 unit as compared to the baseline 
score to the first time of resolution based 
on 12.5 improvement from the first worst 
subscale score during the event. It 
requires at least one day gap between 
the resolution of worsening from first 
course to the onset of second course. 
AAC [1] 


 
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Patient Reported Outcomes: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.008 
All Treated 
OSDI_DET 
Summary of Patients with a 12.5 Point or Greater Deterioration 
from Baseline in the Visual Related Function Subscale Score (Arm 
B– GSK2857916 + Bor/Dex (Vd)) 
Summarize by: dose level. Refer to 
mid205207 (primary_03) Table 6.0003 
for guidance. Include the following 
footnotes: 
(1) Improvement is defined as a 
decrease from the worst subscale score 
of at least 12.5 points. 
(2) Time to 12.5 point deterioration 
assessed only for those subjects 
experiencing a first worsening of at least 
one 12.5 unit as compared to the 
baseline score with complete onset 
date. 
(3) Duration is defined as time from the 
onset of first worsening of at least one 
12.5 unit as compared to the baseline 
score to the first time of resolution based 
on 12.5 improvement from the first worst 
subscale score during the event. It 
requires at least one day gap between 
the resolution of worsening from first 
course to the onset of second course. 
AAC [1] 
NEI-VFQ-25 
6.009 
All Treated 
VFQ_CHG 
Summary of Change in NEI-VFQ-25 Overall Composite Scores 
from Baseline (Arm A – GSK2857916 + Len/Dex (Rd)) 
Summarize by: dose level. Timepoints 
includes EOT visit, last follow-up visit, 
and worst change from baseline. 
AAC [1] 
6.010 
All Treated 
VFQ_CHG 
Summary of Change in NEI-VFQ-25 Overall Composite Scores 
from Baseline (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Summarize by: dose level. Timepoints 
includes EOT visit, last follow-up visit, 
and worst change from baseline. 
AAC [1] 


 
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Patient Reported Outcomes: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.011 
All Treated 
VFQ_CHG 
Summary of Change in NEI-VFQ-25 Subscale Scores from 
Baseline (Arm A – GSK2857916 + Len/Dex (Rd)) 
Summarize by: dose level. Timepoints 
includes EOT visit, last follow-up visit, 
and worst change from baseline. 
AAC [1] 
6.012 
All Treated 
VFQ_CHG 
Summary of Change in NEI-VFQ-25 Subscale Scores from 
Baseline (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Summarize by: dose level. Timepoints 
includes EOT visit, last follow-up visit, 
and worst change from baseline. 
AAC [1] 
EORTC QLQ-C30 
6.013 
All Treated 
QLQ_CHG_DOM Summary of Change in EORTC QLQ-C30 Domain Scores from 
Baseline (Arm A – GSK2857916 + Len/Dex (Rd)) 
Refer to mid205678 (primary_01) Table 
8.0020 for guidance. 
Including score for 15 domains and 
Improvement in EORTC QLQ-C30 
domain score >=10 
AAC [1] 
6.014 
All Treated 
QLQ_CHG_DOM Summary of Change in EORTC QLQ-C30 Domain Scores from 
Baseline (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Refer to mid205678 (primary_01) Table 
8.0020 for guidance. 
Including score for 15 domains and 
Improvement in EORTC QLQ-C30 
domain score >=10 
AAC [1] 
EORTC QLQ-MY20 
6.015 
All Treated 
QLQ_CHG_DOM Summary of Change in EORTC QLQ-MY20 Domain Scores from 
Baseline (Arm A – GSK2857916 + Len/Dex (Rd)) 
Refer to mid205678 (primary_01) Table 
8.0070 for guidance. 
Including score for 4 domains and 
Improvement in EORTC QLQ-MY20 
domain score >=10 
AAC [1] 
6.016 
All Treated 
QLQ_CHG_DOM Summary of Change in EORTC QLQ-MY20 Domain Scores from 
Baseline (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Refer to mid205678 (primary_01) Table 
8.0070 for guidance. 
Including score for 4 domains and 
Improvement in EORTC QLQ-MY20 
domain score >=10 
AAC [1] 


 
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Patient Reported Outcomes: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Compliance of PRO-CTCAE, OSDI, and EORTC QLQ-C30 


 
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Patient Reported Outcomes: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.017 
All Treated 
COMP1 
Summary of Compliance of PRO CTCAE, NEI-VFQ-25, and OSDI 
by Visit and Overall (Arm A – GSK2857916 + Len/Dex (Rd)) 
Summarize by: dose level. Refer to 
mid205678 (primary_07) Table 8.10010 
for guidance. 
• 
Include number and percentage of 
subjects for each assessment. 
• 
Add “Overall” Compliance to 
bottom of table, representing 
compliance over all visits.  
 
Footnotes: 
Note: Percentage is calculated using # 
of subjects remaining in the study at 
given timepoint as 
denominator. 
Note: Subjects are counted as 
remaining in the study at last follow-up 
visit if they have at least one 
recorded follow-up visit. 
Note: Last Follow-up visit is not 
collected for PRO-CTCAE. Subjects 
who show corneal signs per the GSK 
scale at EOT will continue to receive 
only the OSDI and NEI-VFQ-25 
assessments during follow-up for up to 1 
year or until ocular exams are 
completed (whichever comes first). 
Note: The overall compliance rate is the 
number of subjects with an evaluable 
baseline score and at least 
one evaluable post-baseline score. 
AAC [1] 


 
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Patient Reported Outcomes: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.018 
All Treated 
COMP1 
Summary of Compliance of PRO CTCAE, NEI-VFQ-25, and OSDI 
by Visit and Overall (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Summarize by: dose level. Refer to 
mid205678 (primary_07) Table 8.10010 
for guidance. 
• 
Include number and percentage of 
subjects for each assessment. 
• 
Add “Overall” Compliance to 
bottom of table, representing 
compliance over all visits.  
 
Footnote: 
Note: percentage is calculated using # 
of subject remaining in the study at 
given timepoint as denominator. 
AAC [1] 
6.019 
All Treated 
COMP2 
Summary of Compliance of EORTC QLQ-C30 and EORTC QLQ-
MY20 by Visit and Overall (Arm A – GSK2857916 + Len/Dex (Rd)) 
Refer to mid205678 (primary_07) Table 
8.10010 for guidance. 
• 
Include number and percentage of 
subjects for each assessment. 
• 
Add “Overall” Compliance to 
bottom of table, representing 
compliance over all visits.  
 
Footnote: 
Note: Percentage is calculated using # 
of subjects remaining in the study at 
given timepoint as 
denominator. 
Note: The overall compliance rate is the 
number of subjects with an evaluable 
baseline score and at least 
one evaluable post-baseline score. 
AAC [1] 


 
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Patient Reported Outcomes: Tables 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.020 
All Treated 
COMP2 
Summary of Compliance of EORTC QLQ-C30 and EORTC QLQ-
MY20 by Visit and Overall (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Refer to mid205678 (primary_07) Table 
8.10010 for guidance. 
• 
Include number and percentage of 
subjects for each assessment. 
• 
Add “Overall” Compliance to 
bottom of table, representing 
compliance over all visits.  
 
Footnote: 
Note: percentage is calculated using # 
of subject remaining in the study at 
given timepoint as denominator. 
AAC [1] 


 
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15.12.13. Patient Reported Outcomes Figures 
Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
PRO-CTCAE 
6.021 
All Treated 
PRO_STACK Stacked Bar Chart of PRO-CTCAE Score by Attributes and Visit 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
Summarize by: dose level. Refer to 
mid205207 (primary_03) Figure 6.0001 
for guidance. 
For each selected item from PRO-
CTCAE library: create 5 sets of stacked 
bar charts per dose cohort for PRO-
CTCAE score for each of 3 attributes 
(frequency, severity and/or 
interference). 
AAC [1] 
6.022 
All Treated 
PRO_STACK Stacked Bar Chart of PRO-CTCAE Score by Attributes and Visit 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
Summarize by: dose level. Refer to 
mid205207 (primary_03) Figure 6.0001 
for guidance. 
For each selected item from PRO-
CTCAE library: create 5 sets of stacked 
bar charts per dose cohort for PRO-
CTCAE score for each of 3 attributes 
(frequency, severity and/or 
interference). 
AAC [1] 


 
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Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
OSDI 
6.023 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of OSDI 
Total Score by Visit (Arm A – GSK2857916 + Len/Dex (Rd)) 
Summarize by: dose level. Refer to 
mid205678 (primary_07) Figure 
8.10023, 8.10024 & 8.10025 for 
guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, worst case 
post treatment and last follow-up visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note: BSLN = "Baseline", EOT = "End 
of Treatment", LFU = "Last Follow-Up", 
and WCPB = "Worst Case Post-
Baseline". 
Note: Confidence Intervals are 
presented where n>=3. 
AAC [1] 


 
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Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.024 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of OSDI 
Total Score by Visit (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Summarize by: dose level. Refer to 
mid205678 (primary_07) Figure 
8.10023, 8.10024 & 8.10025 for 
guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, worst case 
post treatment and last follow-up visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note 1: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note 2: “BSLN” represents “Baseline”; 
“EOT” represents “End of Treatment”; 
"WCPB" represents "Worst Case Post-
baseline"; "LFU" represents "Last 
Follow-up". 
AAC [1] 


 
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Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
EORTC QLQ-C30 
6.025 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of EORTC 
QLQ-C30 Pain Domain Score by Visit (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
Refer to mid205678 (primary_07) Figure 
8.10037 for guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, and worst 
case post baseline visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note 1: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note 2: “BSLN” represents “Baseline”; 
“EOT” represents “End of Treatment”; 
"WCPB" represents "Worst Case Post-
baseline"; "LFU" represents "Last 
Follow-up". 
AAC [1] 


 
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Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.026 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of EORTC 
QLQ-C30 Pain Domain Score by Visit (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Refer to mid205678 (primary_07) Figure 
8.10037 for guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, and worst 
case post baseline visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note 1: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note 2: “BSLN” represents “Baseline”; 
“EOT” represents “End of Treatment”; 
"WCPB" represents "Worst Case Post-
baseline"; "LFU" represents "Last 
Follow-up". 
AAC [1] 


 
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Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.027 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of EORTC 
QLQ-C30 Fatigue Domain Score by Visit (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
Refer to mid205678 (primary_07) Figure 
8.10038 for guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, and worst 
case post baseline visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note 1: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note 2: “BSLN” represents “Baseline”; 
“EOT” represents “End of Treatment”; 
"WCPB" represents "Worst Case Post-
baseline"; "LFU" represents "Last 
Follow-up". 
AAC [1] 


 
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Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.028 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of EORTC 
QLQ-C30 Fatigue Domain Score by Visit (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Refer to mid205678 (primary_07) Figure 
8.10038 for guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, and worst 
case post baseline visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note 1: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note 2: “BSLN” represents “Baseline”; 
“EOT” represents “End of Treatment”; 
"WCPB" represents "Worst Case Post-
baseline"; "LFU" represents "Last 
Follow-up". 
AAC [1] 


 
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Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.029 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of EORTC 
QLQ-C30 Global Health Status / QoL Domain Score by Visit (Arm 
A – GSK2857916 + Len/Dex (Rd)) 
Refer to mid205678 (primary_07) Figure 
8.10039 for guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, and worst 
case post baseline visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note 1: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note 2: “BSLN” represents “Baseline”; 
“EOT” represents “End of Treatment”; 
"WCPB" represents "Worst Case Post-
baseline"; "LFU" represents "Last 
Follow-up". 
AAC [1] 


 
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Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.030 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of EORTC 
QLQ-C30 Global Health Status / QoL Domain Score by Visit (Arm 
B – GSK2857916 + Bor/Dex (Vd)) 
Refer to mid205678 (primary_07) Figure 
8.10039 for guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, and worst 
case post baseline visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note 1: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note 2: “BSLN” represents “Baseline”; 
“EOT” represents “End of Treatment”; 
"WCPB" represents "Worst Case Post-
baseline"; "LFU" represents "Last 
Follow-up". 
AAC [1] 


 
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Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.031 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of EORTC 
QLQ-C30 Physical Functioning Domain Score by Visit (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Refer to mid205678 (primary_07) Figure 
8.10037 for guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, and worst 
case post baseline visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note 1: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note 2: “BSLN” represents “Baseline”; 
“EOT” represents “End of Treatment”; 
"WCPB" represents "Worst Case Post-
baseline"; "LFU" represents "Last 
Follow-up". 
AAC [1] 


 
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Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.032 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of EORTC 
QLQ-C30 Physical Functioning Domain Score by Visit (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Refer to mid205678 (primary_07) Figure 
8.10037 for guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, and worst 
case post baseline visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note 1: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note 2: “BSLN” represents “Baseline”; 
“EOT” represents “End of Treatment”; 
"WCPB" represents "Worst Case Post-
baseline"; "LFU" represents "Last 
Follow-up". 
AAC [1] 


 
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Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.033 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of EORTC 
QLQ-C30 Role Functioning Domain Score by Visit (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Refer to mid205678 (primary_07) Figure 
8.10037 for guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, and worst 
case post baseline visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note 1: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note 2: “BSLN” represents “Baseline”; 
“EOT” represents “End of Treatment”; 
"WCPB" represents "Worst Case Post-
baseline"; "LFU" represents "Last 
Follow-up". 
AAC [1] 


 
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197 
 
Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.034 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of EORTC 
QLQ-C30 Role Functioning Domain Score by Visit (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Refer to mid205678 (primary_07) Figure 
8.10037 for guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, and worst 
case post baseline visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note 1: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note 2: “BSLN” represents “Baseline”; 
“EOT” represents “End of Treatment”; 
"WCPB" represents "Worst Case Post-
baseline"; "LFU" represents "Last 
Follow-up". 
AAC [1] 


 
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Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
EORTC QLQ-MY20 
6.035 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of EORTC 
QLQ-MY20 Disease Symptom Domain Score by Visit (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Refer to mid205678 (primary_07) Figure 
8.10037 for guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, and worst 
case post baseline visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note 1: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note 2: “BSLN” represents “Baseline”; 
“EOT” represents “End of Treatment”; 
"WCPB" represents "Worst Case Post-
baseline"; "LFU" represents "Last 
Follow-up". 
SAC [1] 


 
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199 
 
Patient Reported Outcomes: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
6.036 
All Treated 
CFB_CI 
Plot of Change from Baseline and Confidence Interval of EORTC 
QLQ-MY20 Disease Symptom Domain Score by Visit (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Refer to mid205678 (primary_07) Figure 
8.10037 for guidance. 
Add a dashed line at y axis=0. 
In addition to treatment visits, also 
include end of treatment, and worst 
case post baseline visits. 
Add arrows showing direction of change 
from baseline: “deterioration” 
“improvement”. 
Add the following footnotes:  
Note 1: Interval shown represents 95% 
confident limits around mean at each 
planned time. 
Note 2: “BSLN” represents “Baseline”; 
“EOT” represents “End of Treatment”; 
"WCPB" represents "Worst Case Post-
baseline"; "LFU" represents "Last 
Follow-up". 
SAC [1] 


 
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15.12.14. ICH Listings 
ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.001 
All Treated 
ES3 
Listing of Reasons for Study Withdrawal (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
ICH E3 
Add footnotes: 
[1] y = years  
[2] Study Day is calculated as the 
number of days from the first dose 
date. 
IA [2], SAC [1] 
1.002 
All Treated 
ES3 
Listing of Reasons for Study Withdrawal (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
Same as above 
IA [1], IA [3], 
SAC [1] 
1.003 
All Treated 
SD2  
Listing of Reasons for Study Treatment Discontinuation (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
ICH E3 
*Add a column for “Treatment” – see 
shell in Section 15.13 
 
Add footnotes: 
[1] y = years  
[2] Study Day is calculated as the 
number of days from the first dose 
date. 
IA [2], SAC [1] 
1.004 
All Treated 
SD2  
Listing of Reasons for Study Treatment Discontinuation (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Same as above  
IA [1], IA [3], 
SAC [1] 


 
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ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Protocol Deviations 
1.005 
All Treated 
DV2 
Listing of Important Protocol Deviations (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
ICH E3 
 
*Do not need last 3 columns titled 
“Deviation Requires Exclusion From” 
 
Add footnote:  
Note: Study Day is calculated as the 
number of days from the first dose 
date. 
SAC [1] 
1.006 
All Treated 
DV2 
Listing of Important Protocol Deviations (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
ICH E3 
 
*Do not need last 3 columns titled 
“Deviation Requires Exclusion From” 
 
Add footnote:  
Note: Study Day is calculated as the 
number of days from the first dose 
date. 
IA [1],  
SAC [1] 
1.007 
All Treated 
IE3 
Listing of Subjects with Inclusion/Exclusion Criteria Deviations (Arm A 
– GSK2857916 + Len/Dex (Rd)) 
ICH E3 
RAPIDO DV at 
SAC [1] 
1.008 
All Treated 
IE3 
Listing of Subjects with Inclusion/Exclusion Criteria Deviations (Arm B 
– GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
RAPIDO DV at 
SAC [1] 
Demographic and Baseline Characteristics 
1.009 
All Treated 
DM2 
Listing of Demographic Characteristics (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
ICH E3 
SAC [1] 


 
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ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.010 
All Treated 
DM2 
Listing of Demographic Characteristics (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
ICH E3 
SAC [1] 
Prior and Concomitant Medications 
1.011 
All Treated 
CM3 
Listing of Concomitant Medications (Arm A – GSK2857916 + Len/Dex 
(Rd)) 
IDSL 
SAC [1] 
1.012 
All Treated 
CM3 
Listing of Concomitant Medications (Arm B – GSK2857916 + Bor/Dex 
(Vd)) 
IDSL 
SAC [1] 
Exposure and Treatment Compliance 
1.013 
All Treated 
OEX8A 
Listing of Exposure Data (Arm A – GSK2857916 + Len/Dex (Rd)) 
ICH E3 
SAC [1] 
1.014 
All Treated 
OEX8A 
Listing of Exposure Data (Arm B – GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
SAC [1] 
Response 
CCI


 
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ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events 
1.017 
All Treated 
AE8  
Listing of All Adverse Events (Arm A – GSK2857916 + Len/Dex (Rd)) 
ICH E3 
 
Add a footnote:  
- Time since 1st dose is the duration 
from the 1st dose of GSK2857916 to 
the start of the adverse event. Time 
since last dose is the duration since 
the latest dose taken (of any study 
treatment component) to the start of 
the adverse event. 
IA [2], SAC [1] 
CCI


 
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ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.018 
All Treated 
AE8  
Listing of All Adverse Events (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Same as above 
 
Add an additional footnote:  
For IDs 2, 3, 6 (Arm B 2.5 mg/kg 
SINGLE) total number of adverse 
events may be overreported due to a 
site related unfixable non-standard 
logging of ongoing events. 
IA [1], IA [3], 
SAC [1] 
1.019 
All Treated 
AE7 
Listing of Subject Numbers for Individual Adverse Events (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
ICH E3 
RAPIDO DV at 
SAC [1] 
1.020 
All Treated 
AE7 
Listing of Subject Numbers for Individual Adverse Events (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
RAPIDO DV at 
SAC [1] 
Serious and Other Significant Adverse Events 
1.021 
All Treated 
AE8 
Listing of Fatal Serious Adverse Events (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
ICH E3 
IA [2], SAC [1] 
1.022 
All Treated 
AE8 
Listing of Fatal Serious Adverse Events (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
ICH E3 
IA [1], IA [3], 
SAC [1] 
1.023 
All Treated 
AE8 
Listing of Non-Fatal Serious Adverse Events (Arm A – GSK2857916 + 
Len/Dex (Rd)) 
ICH E3 
SAC [1] 
1.024 
All Treated 
AE8 
Listing of Non-Fatal Serious Adverse Events (Arm B – GSK2857916 + 
Bor/Dex (Vd)) 
ICH E3 
SAC [1] 
1.025 
All Treated 
AE14 
Listing of Reasons for Considering as a Serious Adverse Event (Arm 
A – GSK2857916 + Len/Dex (Rd)) 
ICH E3 
SAC [1] 
1.026 
All Treated 
AE14 
Listing of Reasons for Considering as a Serious Adverse Event (Arm 
B – GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
SAC [1] 


 
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ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
All Laboratory 
1.027 
All Treated 
LB5A 
Listing of All Laboratory Data for Subjects with Any Value of Potential 
Clinical Importance (Arm A – GSK2857916 + Len/Dex (Rd)) 
ICH E3 
SAC [1] 
1.028 
All Treated 
LB5A 
Listing of All Laboratory Data for Subjects with Any Value of Potential 
Clinical Importance (Arm B – GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
SAC [1] 
1.029 
All Treated 
LB14 
Listing of Laboratory Data with Character Results (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
ICH E3 
SAC [1] 
1.030 
All Treated 
LB14 
Listing of Laboratory Data with Character Results (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
SAC [1] 
1.031 
All Treated 
UR2 
Listing of Urinalysis Data for Subjects with Any Value of Potential 
Clinical Importance (Arm A – GSK2857916 + Len/Dex (Rd)) 
ICH E3 
RAPIDO DV at 
SAC [1] 
1.032 
All Treated 
UR2 
Listing of Urinalysis Data for Subjects with Any Value of Potential 
Clinical Importance (Arm B – GSK2857916 + Bor/Dex (Vd)) 
ICH E3 
RAPIDO DV at 
SAC [1] 
Death 
1.033 
All Treated 
DD2 
Listing of Subject Numbers for Specific Causes of Deaths (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
 
SAC [1] 
1.034 
All Treated 
DD2 
Listing of Subject Numbers for Specific Causes of Deaths (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
 
IA [3], SAC [1] 


 
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15.12.15. Non-ICH Listings 
Non-ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Protocol Deviations 
30.001 
All Treated 
PAN7 
Listing of Visits Impacted by COVID-19 Pandemic (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
 
RAPIDO DV at 
SAC [1] 
30.002 
All Treated 
PAN7 
Listing of Visits Impacted by COVID-19 Pandemic (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
 
RAPIDO DV at 
SAC [1] 


 
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Non-ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Exposure 
30.003 
All Treated 
OEX9 
Summary Listing of Overall Exposure and Dose Modifications 
(Arm A – GSK2857916 + Len/Dex (Rd)) 
*Add Site ID, Subject ID, Component, 
Time on Study Treatment, Dose 
Intensity, and Dose Modification 
Summary 
 
*We do not need the “X Missed 
Doses” category under “Dose 
Modification Summary” 
 
*Add footnotes (for correct order see 
annotated shells):  
[1] Dose intensity (units/interval) is 
the cumulative actual dose divided 
by duration of exposure, where 
interval is 4 weeks for SINGLE and 
SPLIT dosing, and 8 weeks for 
STRETCH dosing. For  dose 
intensity, date of discontinuation is 
the date of last dose.  
For Arm A, each cycle is 4 weeks (28 
days) 
No dose reduction of GSK2857916 
allowed for 1.9 mg/kg STRETCH and 
SINGLE 
IA [2], SAC [1] 


 
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Non-ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
30.004 
All Treated 
OEX9 
Summary Listing of Overall Exposure and Dose Modifications 
(Arm B – GSK2857916 + Bor/Dex (Vd)) 
*Add Site D, Subject ID, Component, 
Time on Study Treatment, Dose 
Intensity, and Dose Modification 
Summary 
 
*We do not need the “X Missed 
Doses” category under “Dose 
Modification Summary” 
 
*Add footnotes (for correct order see 
annotated shells):  
[1] Dose intensity (units/interval) is 
the cumulative actual dose divided 
by duration of exposure, where 
interval is 3 weeks for SINGLE/SPLIT 
doses and 6 weeks for STRETCH 
and S/D STRETCH doses. 
[2] Dose Intensity for BOR and DEX 
calculated per day within a cycle for 
Bortezomib. 
For Arm B, each cycle is 3 weeks (21 
days) 
No dose reduction of GSK2857916 
allowed for 1.9 mg/kg STRETCH and 
SINGLE, and 2.5 mg/kg S/D 
STRETCH 
IA [1], IA [3], 
SAC [1] 
Anti-Drug Antibody 
30.005 
All Treated 
IMM5 
Listing of GSK2857916 Immunogenicity Results (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
 
RAPIDO DV at 
AAC [1] 


 
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Non-ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
30.006 
All Treated 
IMM5 
Listing of GSK2857916 Immunogenicity Results (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
 
RAPIDO DV at 
AAC [1] 
PK 
30.007 
PK GSK2857916 
PK13 
Listing of GSK2857916 (ADC, Total Antibody, cys-mcMMAF) 
Pharmacokinetic Concentration-Time Data (Arm A – 
GSK2857916 + Len/Dex (Rd)) 
Produce Listing by Treatment  
AAC [1] 
30.008 
PK GSK2857916 
PK13 
Listing of GSK2857916 (ADC, Total Antibody, cys-mcMMAF) 
Pharmacokinetic Concentration-Time Data (Arm B – 
GSK2857916 + Bor/Dex (Vd)) 
Produce Listing by Treatment 
AAC [1] 
30.009 
PK Lenalidomide 
25mg  
PK13 
Listing of Lenalidomide Pharmacokinetic Concentration-Time 
Data (Arm A – GSK2857916 + Len/Dex (Rd)) 
Produce Listing by Treatment 
Can delete “dose number” from 
listing 
AAC [1] 
30.010 
PK Lenalidomide 
10mg  
PK13 
Listing of Lenalidomide Pharmacokinetic Concentration-Time 
Data (Arm A – GSK2857916 + Len/Dex (Rd)) 
Produce Listing by Treatment 
Can delete “dose number” from 
listing 
AAC [1] 
30.011 
PK Bortezomib  
PK13 
Listing of Bortezomib Pharmacokinetic Concentration-Time 
Data (Arm B – GSK2857916 + Bor/Dex (Vd)) 
Produce Listing by Treatment 
Can delete “dose number” from 
listing 
Add column for “Route” 
AAC [1] 


 
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15.13. 
Appendix 13: Example Mock Shells for Data Displays 
Mock shells will be available within a RAP Supportive Document. This RAP Supportive Document will contain the final templates applied 
for final SAC.  
 
 
 
 
 
 
 
 
 
 
 
 
 


Signature Page for  207497 TMF-16085540 v1.0
Signature Page for TMF-16085540 v1.0
Reason for signing: Approved
Name: 
Role: Approver
Date of signature: 25-Apr-2023 15:48:45 GMT+0000
Reason for signing: Approved
Name: 
Role: Approver
Date of signature: 25-Apr-2023 16:02:53 GMT+0000
PPD
PPD