Clinical trial NCT03525678
Conditions: Multiple Myeloma
Keywords: Relapsed Refractory multiple myeloma Antibody-drug conjugate Patient-Reported Outcome Version of the Common Term Criteria for Adverse Events Quality of Life Questionnaire 20-item Multiple Myeloma module Multiple Myeloma Quality of Life Questionnaire 30-item Core module
Sponsor: GlaxoSmithKline
Start date: 2018-06-18; Completion date: 2024-09-12
Enrollment: 221 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Multiple myeloma (MM) is an incurable malignancy and accounts for 1 percentage (%) of all cancers and for 10% of all hematologic malignancies. Participants with relapsed/refractory multiple myeloma (RRMM) will be included in this study, to evaluate the efficacy and safety of belantamab mafodotin (GSK2857916) monotherapy. Participants will be treated with belantamab mafodotin monotherapy until disease progression (PD) or unacceptable toxicity and will be followed for Progression Free Survival and Overall survival. The participants will be randomized to receive either frozen belantamab mafodotin at the dose of 2.5 milligram per kilogram (mg/kg) or 3.4 mg/kg administered Intravenously (IV). There will be an independent cohort of participants who will receive a lyophilized configuration of belantamab mafodotin. For participants who discontinued from the study other than Progressive disease (PD), disease evaluation will continue to be performed at 3-week intervals until confirmed PD, death, start of a new anticancer treatment, withdrawal of consent, or end of the study whichever occurs first.

Detailed description:

Arms: arm 1: Participants will receive 2.5 mg/kg frozen liquid belantamab mafodotin. Participants will be administered with frozen liquid belantamab mafodotin via infusion pump every 3 weeks. arm 2: Participants will receive 3.4 mg/kg frozen liquid belantamab mafodotin. Participants will be administered with frozen liquid belantamab mafodotin via infusion pump every 3 weeks. arm 3: Participants in lyophilized arm will receive lyophilized belantamab mafodotin once lyophilized configuration becomes available and enrollment has been completed for frozen liquid arms.
Interventions: intervention 1: Belantamab mafodotin frozen liquid intervention 2: Belantamab mafodotin lyophilized powder
Intervention descriptions: intervention 1: Belantamab mafodotin will be available as frozen liquid. Frozen liquid will be available as 30 milligram (mg)/vial solution in a single use vial with unit dose strength of 2.5 or 3.4 mg/kg. Belantamab mafodotin will be administered as IV solution over at least 30 minutes. Frozen belantamab mafodotin will be diluted in 0.9 percent saline and administered via infusion pump. intervention 2: Belantamab mafodotin will be available as lyophilized powder. Lyophilized powder will be available as 100 mg/vial in single-use vial for reconstitution with unit dose strength of 3.4 mg/kg. Lyophilized belantamab mafodotin will be reconstituted using water for injection and diluted with saline before use.

Protocol documents:
Prot_002.pdf: 
Protocol
Study ID:  205678
Official Title of Study: Reporting and Analysis Plan for A Phase II, Open Label, 
Randomized, Two-Arm Study to Investigate the Efficacy and Safety of Two Doses of the 
Antibody Drug Conjugate GSK2857916 in Participants with Multiple Myeloma Who Had 
3 or More Prior Lines of Treatment, Are Refractory to Proteasome Inhibitor and an 
Immunomodulatory Agent and Have Failed an Anti-CD38 Antibody (DREAMM 2)
NCTID: NCT03525678
Date of Document: 19 November 2021


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TITLE PAGE 
Protocol Title: A Phase II, Open Label, Randomized, Two-Arm Study to Investigate the 
Efficacy and Safety of Two Doses of the Antibody Drug Conjugate GSK2857916 in 
Participants with Multiple Myeloma Who Had 3 or More Prior Lines of Treatment, Are 
Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed 
an Anti-CD38 Antibody (DREAMM 2) 
Protocol Number: 205678/ Amendment 06  
Compound Number: 
GSK2857916  
Brief Title: Open-label, randomized study of two doses of GSK2857916 in participants 
with relapsed/refractory multiple myeloma who have failed prior treatment with an anti-
CD38 antibody 
 
Study Phase: Phase II 
 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Regulatory Agency 
Identifying 
Number(s): 
Registry 
ID 
IND number 
119333 
EudraCT number 
2017-004810-25 
 
 
 
Approval Date: 19 Nov 2021 
©2021 GSK group of companies or its licensor. All rights reserved. Unauthorized 
copying or use of this information is prohibited. 


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SPONSOR SIGNATORY 
Protocol Title: A Phase II, Open Label, Randomized, Two-Arm Study to Investigate the 
Efficacy and Safety of Two Doses of the Antibody Drug Conjugate GSK2857916 in 
Participants with Multiple Myeloma Who Had 3 or More Prior Lines of Treatment, Are 
Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed 
an Anti-CD38 Antibody (DREAMM 2) 
Protocol Number: 
205678/ Amendment 06 
Compound Number: GSK2857916 
 
 
 
 
Timothy Crossman, BMBS MRes  
Group Sr. Director, Clinical Development Lead 
 
The signed page is a separate document. 
 
Date 
 
 
Medical Monitor Name and Contact Information can be found in the Study 
Reference Manual. 
 
 
 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Document Identifier 
Amendment 6 
19 Nov 2021 
TMF-13990464 
Amendment 5 
08-Oct-2020 
2017N330177_06 
Amendment 4 
21-Oct-2019 
2017N330177_05 
Amendment 3 
17-Dec-2018 
2017N330177_04 
Amendment 2 (Republishing) 
04-Sep-2018 
2017N330177_03 
Amendment 2 
30-Aug-2018 
2017N330177_02 
Amendment 1 
02-Apr-2018 
2017N330177_01 
Original Protocol 
18-Jan-2018 
2017N330177_00 
 
Amendment 06: 19 Nov 2021 
Overall Rationale for the Amendment:  
The protocol has been amended to provide updates including the addition of the end of 
study definition section (Section 4.6) and continued access to study intervention after the 
end of the study section (Post Analysis Continued Treatment [PACT]) (Section 6.9). 
Section # and Name Description of Change 
Brief Rationale  
Section 1.1 Synopsis 
Additional content to the overall study 
has been added which includes PACT 
implementation and End of Study 
definition 
To introduce the approved 
standard language for 
belantamab mafodotin studies 
implementing PACT  
Section 2.4.4 
Pharmacokinetics 
and 
Pharmacodynamics 
Revision of pharmacokinetics and 
pharmacodynamics section as per 
latest information available in IB 
Section updated as per latest 
information available in IB 
Section 4.1 Overall 
Design 
Additional content added to align to 
PACT implementation 
To introduce the approved 
standard language for 
belantamab mafodotin studies 
implementing PACT 
Section 4.6 End of 
Study Definition 
New section added to align to PACT 
implementation and additional content 
added related to PACT 
To introduce the approved 
standard language for 
belantamab mafodotin studies 
implementing PACT  
Section 6.9 
Continued Access to 
Study Intervention 
New section added to align to PACT 
implementation and additional content 
added related to PACT  
To introduce the approved 
standard language for 
belantamab mafodotin studies 
implementing PACT  


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Section # and Name Description of Change 
Brief Rationale  
after the End of the 
Study 
Section 8.2.1 Time 
Period and 
Frequency for 
Collecting AE and 
SAE Information  
Additional content added to align to 
PACT implementation 
To introduce the approved 
standard language for 
belantamab mafodotin studies 
implementing PACT  
 


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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3 
1. 
PROTOCOL SUMMARY ........................................................................................ 10 
1.1. 
Synopsis ..................................................................................................... 10 
1.2. 
Schedule of Activities (SoA) ........................................................................ 18 
2. 
INTRODUCTION .................................................................................................... 32 
2.1. 
Study Rationale .......................................................................................... 32 
2.2. 
Background – BCMA and Multiple Myeloma ............................................... 33 
2.3. 
Antibody-Drug Conjugate Belantamab Mafodotin ....................................... 33 
2.4. 
Human Experience with Belantamab Mafodotin .......................................... 34 
2.4.1. 
Thrombocytopenia ....................................................................... 36 
2.4.2. 
Corneal Events ............................................................................ 36 
2.4.3. 
Infusion-related reactions ............................................................. 36 
2.4.4. 
Pharmacokinetics and Pharmacodynamics .................................. 37 
2.5. 
Benefit / Risk Assessment .......................................................................... 38 
2.5.1. 
Risk Assessment ......................................................................... 38 
2.5.2. 
Benefit Assessment ..................................................................... 42 
2.5.3. 
Overall Benefit-Risk Conclusions ................................................. 42 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 42 
4. 
STUDY DESIGN .................................................................................................... 44 
4.1. 
Overall Design ............................................................................................ 44 
4.2. 
Number of Participants ............................................................................... 48 
4.3. 
Participant Completion ................................................................................ 49 
4.4. 
Scientific Rationale for Study Design .......................................................... 49 
4.5. 
Dose Justification ........................................................................................ 50 
4.6. 
End of Study Definition ............................................................................... 53 
5. 
STUDY POPULATION ........................................................................................... 54 
5.1. 
Inclusion Criteria ......................................................................................... 54 
5.2. 
Exclusion Criteria ........................................................................................ 56 
5.3. 
Lifestyle Restrictions ................................................................................... 58 
5.4. 
Screen Failures........................................................................................... 58 
6. 
TREATMENTS ....................................................................................................... 58 
6.1. 
Belantamab Mafodotin Treatments Administered ........................................ 59 
6.2. 
Dose Modification ....................................................................................... 59 
6.2.1. 
Adjustments Due to Body Weight ................................................ 60 
6.2.2. 
Dose Reductions for Toxicity ....................................................... 60 
6.2.3. 
Corneal Supportive Care Guidelines ............................................ 65 
6.3. 
Method of Treatment Assignment ............................................................... 66 
6.4. 
Blinding ....................................................................................................... 67 
6.5. 
Preparation/Handling/Storage/Accountability .............................................. 67 
6.6. 
Treatment Compliance ................................................................................ 67 
6.7. 
Concomitant Therapy.................................................................................. 68 
6.7.1. 
Permitted Medication(s) ............................................................... 68 
6.7.2. 
Prohibited Medication(s) .............................................................. 68 


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6.7.3. 
Prohibited Device(s) .................................................................... 69 
6.8. 
Treatment after the End of the Study .......................................................... 69 
6.9. 
Continued Access to Study Intervention after the End of the Study ............ 69 
7. 
DISCONTINUATION CRITERIA ............................................................................. 70 
7.1. 
Discontinuation of Study Treatment ............................................................ 70 
7.2. 
Safety Stopping Criteria .............................................................................. 71 
7.2.1. 
Liver Chemistry Stopping Criteria ................................................ 71 
7.2.2. 
Study Treatment Restart or Rechallenge ..................................... 72 
7.2.3. 
Left Ventricular Ejection Fraction (LVEF) Stopping Criteria .......... 72 
7.2.4. 
Corneal Event Stopping Criteria ................................................... 72 
7.2.5. 
Infusion-Related Reaction Management and Stopping 
Criteria ......................................................................................... 73 
7.2.6. 
Allergic and Anaphylactic Reaction Stopping Criteria ................... 73 
7.3. 
Withdrawal from the Study .......................................................................... 73 
7.4. 
Lost to Follow Up ........................................................................................ 73 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 74 
8.1. 
Efficacy Assessments ................................................................................. 77 
8.1.1. 
Independent Review Committee .................................................. 79 
8.2. 
Adverse Events........................................................................................... 79 
8.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 79 
8.2.2. 
Method of Detecting AEs and SAEs ............................................. 80 
8.2.3. 
Follow-up of AEs and SAEs ......................................................... 80 
8.2.4. 
Regulatory Reporting Requirements for SAEs ............................. 80 
8.2.5. 
Cardiovascular and Death Events ................................................ 81 
8.2.6. 
Disease-Related Events and/or Disease-Related ........................ 81 
8.2.7. 
Adverse Events of Special Interest .............................................. 81 
8.2.8. 
Pregnancy ................................................................................... 81 
8.2.9. 
Ocular Examinations and Procedures .......................................... 82 
8.2.10. 
Ocular Sub-Study Examinations .................................................. 83 
8.2.10.1. Monocular prophylaxis ................................................ 83 
8.2.10.2. Monocular treatment ................................................... 84 
8.2.10.3. Sub-Study Exams ....................................................... 85 
8.3. 
Treatment of Overdose ............................................................................... 85 
8.4. 
Safety Assessments ................................................................................... 85 
8.4.1. 
Physical Examinations ................................................................. 86 
8.4.2. 
ECOG Performance Status .......................................................... 86 
8.4.3. 
Vital Signs .................................................................................... 86 
8.4.3.1. 
First Infusion ............................................................... 86 
8.4.3.2. 
Subsequent Infusions ................................................. 86 
8.4.4. 
Echocardiogram........................................................................... 86 
8.4.5. 
Laboratory Assessments ............................................................. 86 
8.4.6. 
Patient-Reported Outcome Version of the Common Term 
Criteria for Adverse Events (PRO-CTCAE) .................................. 87 
8.4.7. 
Visual Function Questionnaires ................................................... 87 
8.4.7.1. 
National Eye Institute Visual Function 
Questionnaire-25 ........................................................ 88 
8.4.7.2. 
The Ocular Surface Disease Index ............................. 88 
8.5. 
Pharmacokinetics ....................................................................................... 88 
8.5.1. 
Blood Sample Collection for Pharmacokinetics ............................ 88 


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8.5.2. 
Pharmacokinetic Sample Analysis ............................................... 88 
8.6. 
Immunogenicity........................................................................................... 89 
8.7. 
Translational Research ............................................................................... 89 
8.8. 
Genetics ..................................................................................................... 89 
8.9. 
Tumor Biomarker Analysis .......................................................................... 90 
8.9.1. 
sBCMA Sample Analysis ............................................................. 90 
8.9.2. 
Potential Tumor Related Biomarkers ........................................... 90 
8.10. 
Evaluation of Anti-Cancer Activity ............................................................... 91 
8.11. 
Health-Related Quality-of-Life ..................................................................... 91 
8.11.1. 
European Organization for Research and Treatment of 
Cancer Quality of Life Questionnaire 30-item Core module 
(EORTC QLQ-C30) ..................................................................... 92 
8.11.2. 
European Organization for Research and Treatment of 
Cancer Quality of Life Questionnaire 20-item Multiple 
Myeloma module (EORTC QLQ-MY20) ....................................... 92 
8.11.3. 
Qualitative Telephone Interviews (Patient Interviews) .................. 92 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 93 
9.1. 
Hypothesis Testing ..................................................................................... 93 
9.2. 
Sample Size Determination ........................................................................ 93 
9.3. 
Sample Size Sensitivity ............................................................................... 94 
9.4. 
Populations for Analysis .............................................................................. 95 
9.5. 
Statistical Analyses ..................................................................................... 95 
9.5.1. 
Efficacy Analyses ......................................................................... 95 
9.5.2. 
Safety Analyses ........................................................................... 97 
9.5.3. 
Analyses of Health-Related Quality of Life Data........................... 98 
9.5.4. 
Pharmacokinetic Analyses ........................................................... 98 
9.5.4.1. 
Pharmacokinetic Data Analyses ................................. 98 
9.5.4.2. 
Statistical Analysis of Pharmacokinetic Data .............. 99 
9.5.5. 
Pharmacokinetic/Pharmacodynamic Analyses ............................. 99 
9.5.6. 
Translational Research Analyses ............................................... 100 
9.5.6.1. 
Analysis of Novel Biomarker Data ............................ 100 
9.5.6.2. 
Analysis of Genetic Data .......................................... 100 
9.5.6.3. 
Exploratory Analyses of DNA and Protein Data ........ 100 
9.5.7. 
Analyses of Immunogenicity Data .............................................. 100 
9.5.8. 
Other Analyses .......................................................................... 100 
9.5.9. 
Interim Analyses ........................................................................ 101 
9.5.9.1. 
Futility Stopping Rule Based on Group 
Sequential Design .................................................... 101 
9.5.9.2. 
Additional Comparative Futility Stopping Rule 
Based on Bayesian Approach .................................. 102 
10. REFERENCES ..................................................................................................... 104 
11. APPENDICES ...................................................................................................... 109 
11.1. 
Appendix 1: Abbreviations and Trademarks .............................................. 109 
11.2. 
Appendix 2: Clinical Laboratory Tests ....................................................... 114 
11.3. 
Appendix 3: Study Governance Considerations ........................................ 115 
11.4. 
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ..................................... 120 
11.5. 
Appendix 5: Contraceptive Guidance and Collection of Pregnancy 
Information ................................................................................................ 126 


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11.6. 
Appendix 6: Genetics ................................................................................ 129 
11.7. 
Appendix 7: Liver Safety: Required Actions and Follow-up 
Assessments and Study Treatment Rechallenge Guidelines .................... 130 
11.7.1. 
Liver Safety Drug Restart or Re-Challenge Guidelines .............. 132 
11.7.1.1. Re-challenge Following Liver Stopping Events 
that are Possibly Related to Study Treatment ........... 132 
11.7.1.2. Re-challenge Following Transient Liver 
Stopping Events Not Related to Study 
Treatment ................................................................. 134 
11.7.2. 
References ................................................................................ 135 
11.8. 
Appendix 8: ECOG Performance Status ................................................... 136 
11.9. 
Appendix 9: GSK/KVA Scale and Mitigation Strategy for 
Belantamab Mafodotin Treatment-Related Corneal Events ...................... 137 
11.10. Appendix 10: Modified Diet in Renal Disease (MDRD) Formula ................ 140 
11.11. Appendix 11: Protocol Amendment History ............................................... 141 
11.12. Appendix 12: Statistical Considerations for Section 10.5.9.2 
Additional Comparative Futility Stopping Rule Based on Bayesian 
Approach .................................................................................................. 168 
11.13. Appendix 13: Home Healthcare and Telemedicine Approaches ................ 171 
 
 
LIST OF TABLES 
PAGE 
Table 1 
Schedule of Activities - Screening Assessments .................................... 19 
Table 2 
Schedule of Activities – On Study Assessments..................................... 21 
Table 3 
Schedule of Activities: End of Treatment (EOT) and Follow-Up 
Assessments .......................................................................................... 27 
Table 4 
Ocular Sub-Study Schedule of Activities (Selected Sites Only) .............. 31 
Table 5 
Risk Assessment and Mitigation Strategy............................................... 38 
Table 6 
Objectives and Endpoints for Study 205678 - Belantamab 
Mafodotin in RRMM Participants Previously Treated with an Anti-
CD38 Antibody ....................................................................................... 43 
Table 7 
Summary of Investigator-Assessed Best Response (with 
Confirmation; Study BMA117159 Part 1) ................................................ 51 
Table 8 
Summary of Predicted Mean Response and Mean ≥Grade 2 
Corneal Event* and 95% Credible Intervals (Parts 1 and 2, Study 
BMA117159) .......................................................................................... 53 
Table 9 
Criteria for Determining Adequate Organ System Function .................... 55 
Table 10 
Permitted Dose Reductions .................................................................... 60 
Table 11 
Dose Modification Guidelines for Belantamab Mafodotin-Related 
Adverse Events ...................................................................................... 61 


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Table 12 
General Dose Modification and Management Guidelines for 
Drug- related Adverse Events Not Otherwise Specifieda ........................ 63 
Table 13 
Dose Modification Guidelines for Belantamab Mafodotin 
Treatment-Related Corneal Events ........................................................ 64 
Table 14 
List of Clinical Laboratory Tests ............................................................. 76 
Table 15 
Statistical Power Scenarios .................................................................... 94 
Table 16 
Analysis Populations Defined for the Study ............................................ 95 
Table 17 
Statistical Analysis Methods for Efficacy Endpoints ................................ 96 
Table 18 
Statistical Analysis Methods for Safety Endpoints .................................. 98 
Table 19 
Probabilities of Crossing Boundaries at the Interim or Final ORR 
Analysis based on Group Sequential Design ........................................ 101 
Table 20 
Probabilities of Stopping for Futility at the Interim or Claiming 
Efficacy at the Final ORR Analysis based on Both Futility Rules .......... 102 
Table 21 
Prophylactic Measures for Corneal Events Associated with 
Belantamab Mafodotin a ....................................................................... 138 
Table 22 
GSK/KVA Scale for Corneal Events Associated with Belantamab 
Mafodotin a ........................................................................................... 138 
Table 23 
Guidance on GSK/KVA Scale Grading Based on Changes in 
Visual Acuity ........................................................................................ 139 
Table 24 
Posterior Probabilities of (Arm 1 Response Rate > Arm 2 
Response Rate) at Interim Analyses .................................................... 169 
Table 25 
Scenarios of Simulation Studies to Evaluate Probabilities of 
Stopping for Futility .............................................................................. 170 
 
LIST OF FIGURES 
PAGE 
Figure 1 
Study 205678 Schematic ....................................................................... 46 
Figure 2 
Fitted Dose-Response Plot for ORR and ≥ Grade 2 Corneal 
Event Rate ............................................................................................. 52 
Figure 3 
Liver Chemistry Stopping Criteria – Liver Stopping Event 
Algorithm ................................................................................................ 71 
Figure 4 
Ocular prophylaxis schematic ................................................................. 84 
 


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


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


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


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


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will be performed during Screening, prior to the first dose of Cycle 1, and during each 
cycle of treatment as illustrated in the Schedule of Activities. 
The study will include 1 interim analysis for futility. If one arm is discontinued as a result 
of the interim analysis, participants will be offered the opportunity to receive treatment at 
the dose that is continuing, or at the original dose upon re-consenting.  
As part of an ocular sub-study, approximately 30 participants (~15 per dose level) will be 
evaluated to study the effect of ophthalmic topical corticosteroids on belantamab 
mafodotin-associated corneal findings and to further characterize these findings. 
Number of Participants: The sample size calculation was performed using East 6.4 
software as a starting point, based on the ORR comparison between the belantamab 
mafodotin arm and the historical control. Based on the simulation results with the 
planned sample size of 65 participants there is 86.90% power to reject the null hypothesis 
within each arm with a 1-sided type I error of 1.23%. 
Approximately 170 participants were initially planned to be screened to enroll a 
minimum of 155 participants at approximately 60 investigational sites globally. A 
minimum of 130 participants (65/arm) were planned to be enrolled to 2 arms receiving 
frozen liquid solution of belantamab mafodotin, which includes ~30 participants from the 
ocular sub-study. Approximately 200 participants will be enrolled onto the frozen liquid 
portion of the study.  
Approximately, twenty-five additional participants will be enrolled into the independent 
lyophilized drug product cohort. 
Treatment Groups and Duration: In this two-arm randomized study, belantamab 
mafodotin will be administered at 2 dose levels (2.5 mg/kg or 3.4 mg/kg) to participants 
by IV infusion on the Q3W schedule at the study site. The dose will be based on actual 
body weight calculated at baseline and may be reduced to address toxicities according to 
protocol guidelines. 
Belantamab mafodotin will be administered on Day 1 of each cycle. Premedication is not 
required unless deemed medically necessary by the investigator, in which case it should 
be administered according to institutional recommendations. If an infusion-related 
reaction (IRR) occurs during administration, the infusion rate may be reduced or halted at 
the discretion of the investigator depending on the severity of the symptoms.  
Participants will be treated until disease progression or until unacceptable toxicity.  
End of Treatment and End of Study Definitions: 
The study will end when all participants have either died, progressed, withdrawn consent, 
or have been followed for a minimum of 39 months from the time the last participant 
receives their first dose of study treatment (LSFD). 
Following 39 months post LSFD, a Post Analysis Continued Treatment (PACT) will be 
implemented. The study 205678 (DREAMM-2) will be closed. At this time, the 


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collection of data for all recruited participants who no longer receive study treatment will 
stop entirely and 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 
and only SAEs, overdose and pregnancy cases, and pre-specified ocular data will be 
reported directly to GSK. 
Inclusion Criteria: Participants are eligible to be included in the study only if all the 
following criteria apply: 
1. Provide signed written informed consent, which includes compliance with the 
requirements and restrictions listed in the consent form 
2. Male or female, 18 years or older (at the time consent is obtained)  
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 
4. Histologically or cytologically confirmed diagnosis of MM as defined in IMWG, 
2014 criteria, and  
a. Has undergone stem cell transplant or is considered transplant ineligible, and 
 
b. Has failed at least 3 prior lines of anti-myeloma treatments, including an anti-
CD38 antibody (e.g., daratumumab) alone or in combination, and is refractory 
to an immunomodulatory agent (i.e., lenalidomide or pomalidomide), and to a 
proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib). 
Refractory myeloma is defined as disease that is nonresponsive while on 
primary or salvage therapy, or progresses within 60 days of last therapy. 
Nonresponsive disease is defined as either failure to achieve at least minimal 
response or development of progressive disease (PD) while on therapy. 
 
5. Has measurable disease with at least one of the following: 
a. Serum M-protein 0.5 g/dL (5 g/L) 
b. Urine M-protein 200 mg/24h 
c. Serum FLC assay: Involved FLC level 10 mg/dL (100 mg/L) and an 
abnormal serum free light chain ratio (<0.26 or >1.65) 
6. Participants with a history of autologous stem cell transplant are eligible for study 
participation provided the following eligibility criteria are met: 
a. transplant was >100 days prior to study enrolment 
b. no active infection(s) 
c. participant meets the remainder of the eligibility criteria outlined in this 
protocol 
7. Adequate organ system function. 
8. Female Participants: Contraceptive use by men or women should be consistent with 
local regulations regarding the methods of contraception for those participating in 
clinical studies.  
 


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A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditions applies: 
• 
Is not a woman of childbearing potential (WOCBP) 
 
OR 
• 
Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of <1% per year), preferably with low user dependency, during the 
intervention period and for at least 80 days after the last dose of study 
intervention and agrees not to donate eggs (ova, oocytes) for the purpose of 
reproduction during this period. The investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of 
study intervention. 
 
A WOCBP must have a negative highly sensitive serum pregnancy test (as 
required by local regulations) within 72 hours before the first dose of study 
intervention.  
 
The investigator is responsible for review of medical history, menstrual history, 
and recent sexual activity to decrease the risk for inclusion of a woman with an 
early undetected pregnancy. 
9. Male Participants: Contraceptive use by men or women should be consistent with 
local regulations regarding the methods of contraception for those participating in 
clinical studies.  
 
Male participants are eligible to participate if they agree to the following during the 
intervention period and for at least 140 days:  
• 
Refrain from donating sperm 
 
PLUS either: 
• 
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long term and persistent basis) and agree to remain abstinent.  
 
OR 
• 
Must agree to use contraception/barrier as detailed below: 
 
Agree to use a male condom and female partner to use an additional highly 
effective contraceptive method with a failure rate of <1% per year as when 
having sexual intercourse with a woman of childbearing potential who is not 
currently pregnant.  
10. All prior treatment-related toxicities (defined by National Cancer Institute- Common 
Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03 must be ≤Grade 1 
at the time of enrolment except for alopecia and Grade 2 peripheral neuropathy. 


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


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b. Evidence of current clinically significant uncontrolled arrhythmias, including 
clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd 
degree atrioventricular (AV) block. 
c. 
History of myocardial infarction, acute coronary syndromes (including 
unstable angina), coronary angioplasty, or stenting or bypass grafting within 
six months of Screening. 
d. Class III or IV heart failure as defined by the New York Heart Association 
functional classification system 
e. 
Uncontrolled hypertension 
14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs 
chemically related to belantamab mafodotin, or any of the components of the study 
treatment. 
15. Pregnant or lactating female. 
16. Active infection requiring antibiotic, antiviral, or antifungal treatment. 
17. Known HIV infection. 
18. Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody 
(HBcAb at screening or within 3 months prior to first dose of study treatment) 
19. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at 
screening or within 3 months prior to first dose of study treatment.  
Note: Participants with positive Hepatitis C antibody due to prior resolved disease 
can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. 
Note: Hepatitis RNA testing is optional and participants with negative Hepatitis C 
antibody test are not required to also undergo Hepatitis C RNA testing. 
 
1.2. 
Schedule of Activities (SoA) 
All assessments planned for participants in Study 205678 are shown in Table 1 
(Screening), Table 2 (On Study Assessments), and Table 3 (End of Treatment and Follow 
Up Assessments).  
Assessments for participants in the ocular sub-study are shown in Table 4. Participants 
who are enrolled into the lyophilized configuration cohort of belantamab mafodotin 
(Figure 1) will follow the same assessments and procedures as the main study.  
The details of these assessments are provided in footnotes to the table, with more details 
provided in Section 8. 
 


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


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


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


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


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


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


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


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


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


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


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Study Assessments 
EOT Visit1 
PFS 
Follow-up2 
OS 
Follow-
Up3 
Notes 
BM for disease 
assessment 
Only if CR has been 
achieved by this visit, or 
suspected PD not evident 
otherwise 
Only if CR has been 
achieved by this visit, or 
suspected PD not evident 
otherwise 
 
should be used throughout the study (i.e., if CT scan was used as 
baseline, participant needs to be followed by CT scans). Plasmacytoma 
measurements should be taken from the CT portion of the PET/CT, or 
MRI scans, or dedicated CT scans where applicable. For participants 
with skin only involvement, skin lesions should be measured with a ruler. 
Measurement of tumor size will be determined by the Sum of the 
Products of the maximal perpendicular diameters of measured lesions 
(SPD). Digital copies of all scans must be maintained at the investigator 
site as source document.  
11. If the last radiographic assessment occurred ≥8 weeks prior to the 
participant’s withdrawal from study treatment, and PD has NOT been 
documented, –a new assessment for extramedullary disease should be 
obtained at EOT. If participant continues in PFS follow-up, perform scans 
for extramedullary disease as clinically indicated. 
12. Germany: no PET/CT to confirm CR or sCR will be performed until 
approved by the German Federal Office of Radiation Protection until 
further notice.  
13. Only required for participants with IgD/E myeloma, where serum m-
component cannot be followed otherwise. 
Bone marrow biopsy to 
assess sCR by IHC15 
Only if CR has been 
achieved on this visit 
Only if CR have been 
achieved on this visit 
 
Biomarkers 
Soluble BCMA (serum)  
X 
 
 
cfDNA (plasma) 
X  
 
 
Optional 
Optional tissue sample 
at PD for BCMA16 
At time of PD 
At time of PD 
 
Health Outcomes 
PRO-CTCAE 
X 
 
 
NEI-VFQ-25 
X 
X 
X17 
OSDI 
X 
X 
X17 
EORTC-QLQ-C30 
X 
 
 
EORTC-QLQ-MY20  
X 
 
 
Patient Interview (PRO) 
18 
X 
 
 
Survival Status phone 
call 
 
 
X 


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


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


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


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


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moiety of belantamab mafodotin is produced as an afucosylated form that generates an 
enhanced antibody-dependent cellular cytotoxicity (ADCC) response upon binding to 
FcRIIIa receptors on the surface of human immune effector cells. The antibody is 
conjugated to the microtubule inhibitor monomethyl auristatin-F (MMAF).  
Upon binding to the cell surface, belantamab mafodotin is rapidly internalized and the 
active drug (cys-mcMMAF) is released inside the cell. The cys-mcMMAF moiety 
disrupts microtubule networks, leading to cell cycle arrest and apoptosis (ADC 
mechanism) [Alley, 2009; Pettit, 1998]. This dual mechanism of action of belantamab 
mafodotin (ADCC and microtubule disruption) enables anti-tumor activity on both 
dividing and non-dividing cells. In addition, when MM cell lines expressing BCMA are 
exposed to belantamab mafodotin, it may act as an inducer of immunogenic cell death 
(ICD) [Kroemer, 2013; Krysko, 2012], representing a potential third mechanism of 
action. Exposure of dendritic cells to tumor cells undergoing ICD induces an antigen-
specific T-cell response, and if it acts similarly in humans could induce the patient’s own 
immune response against the MM tumor. Expression of the target of belantamab 
mafodotin (BCMA) is restricted to B cells at later stages of differentiation. The target is 
also present on tumor cells of all patients with MM [Tai, 2015; Tai, 2006]. 
2.4. 
Human Experience with Belantamab Mafodotin 
Single-agent belantamab mafodotin has demonstrated to have a strong single-agent 
activity with a well-defined manageable safety profile in heavily pre-treated participants 
with RRMM (Q3W schedule via IV administration). Safety data for single-agent 
belantamab mafodotin were pooled (data as of 20 September 2019) for study 205678 
(DREAMM-2; NCT03525678) and supportive FTIH study BMA117159 (DREAMM-1; 
NCT02064387), by treatment cohorts of 2.5 mg/kg and 3.4 mg/kg. 
FTIH study BMA117159/DREAMM-1 
In the FTIH DREAMM-1 study, which consisted of a dose escalation phase (Part 1, 
n=38) and a dose expansion phase (Part 2, n=35), as of the primary analysis cut-off date 
of 31 August 2018, a total of 73 participants with RRMM received at least 1 dose of 
belantamab mafodotin [GSK2857916 GlaxoSmithKline Document Number 
2013N175128_09, 2021; Trudel, 2019].  
As of the efficacy cut-off date of 31 August 2018, a total of 35 participants were treated 
at the 3.4 mg/kg dose in Part 2 of the DREAMM-1 study. Participants were heavily 
pre-treated: 57% of participants had 5 or more prior lines of therapy. The ORR was 60% 
(95% CI: 42.1, 76.1): comprised of PR, 6%; VGPR, 40%; CR, 9%; and stringent CR 
(sCR), 6%. The median duration of response (DoR) was 14.3 months (95% CI: 10.6, 
NR). The median PFS (mPFS) in this population was 12.0 months (95% CI: 3.1, not 
estimable [NE]). For participants refractory to both immunomodulatory agents and PIs (n 
= 32/35), the confirmed ORR was 56% (95% CI: 37.7, 73.6) and mPFS was 7.9 months 
(95% CI: 2.3, NE) [Trudel, 2019].  


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Phase II study 205678/DREAMM-2 
The ongoing Phase II study 205678/DREAMM-2 is evaluating these two IV single agent 
doses (2.5 and 3.4 mg/kg) administered Q3W until disease progression in participants 
who have failed at least 3 prior lines of anti-myeloma therapy, including an anti-CD38 
antibody, and who are refractory to an immunomodulatory agent and a proteasome 
inhibitor. A total of 194 participants received frozen drug product in the main cohort and 
24 participants received 3.4 mg/kg lyophilized drug product. Primary analysis data from 
this study indicated no new safety signals, and the profile of adverse events was similar to 
the experience in the DREAMM-1 study for both arms. Both dose levels, 2.5 and 3.4 
mg/kg, were shown to have a positive benefit/risk profile [Li, 2017; Lonial, 2020].  
As of the cut-off date of 31 January 2020, the study met its primary endpoint for ORR in 
both the 2.5 mg/kg [ORR 31% (97.5% CI 21.7, 43.6)] and 3.4 mg/kg [ORR 35% 
(97.5%CI 24.8, 47.0)] frozen treatments, and the benefit of belantamab mafodotin was 
supported by the secondary endpoints. The median DoR was 11.0 months (95% CI: 4.2, 
NR) at 2.5 mg/kg and 6.2 months (95% CI: 4.8, NR) at 3.4 mg/kg. The mPFS in this 
population was 2.8 months (95% CI: 1.6, 3.6) and 3.9 months (95% CI: 2.0, 5.8), 
respectively and the median Overall Survival (mOS) was 13.7 months (95% CI: 9.9, NR) 
at 2.5 mg/kg and 13.8 months (95% CI: 10.0, NR) at 3.4 mg/kg. Positive clinical activity 
was also demonstrated at the 3.4 mg/kg lyophilised dose [ORR 52% (97.5% CI 28.9, 
74.5)].  
 
Safety 
Single-agent belantamab mafodotin was demonstrated to have a manageable safety 
profile in heavily pre-treated participants with RRMM. Safety data for single-agent 
belantamab mafodotin were pooled (data as of 20 September 2019) for DREAMM-2 
study and supportive FTIH study DREAMM-1 by treatment cohorts of 2.5 mg/kg and 
3.4 mg/kg. 
The most common AEs in both treatment cohorts were keratopathy (corneal epithelium 
changes observed on ophthalmic examination), thrombocytopenia and anemia. The 
incidence of AEs, including Grade 3/4 AEs was comparable between belantamab 
mafodotin 2.5 mg/kg and 3.4 mg/kg cohorts. Adverse events leading to dose delays, and 
reductions were less frequent in 2.5 mg/kg cohort, 51% and 32% compared with the 3.4 
mg/kg cohort, 67% and 52%, respectively. AEs leading to permanent treatment 
discontinuation occurred in 10% and 11% of participants in the 2.5 and 3.4 mg/kg 
cohorts, respectively. More participants in the 3.4 mg/kg cohort experienced SAEs (50%) 
and fatal SAEs (6%) compared with the 2.5 mg/kg cohort (41% and 3%, respectively). 
Single agent belantamab mafodotin 2.5 mg/kg was selected as the recommended dose 
based on comparable efficacy with a more favorable safety profile (i.e. lower incidence 
of thrombocytopenia and neutropenia and less frequent dose delays or reductions) 
compared with the 3.4 mg/kg dose. 
 


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


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2.4.4. 
Pharmacokinetics and Pharmacodynamics 
The pharmacokinetics and pharmacodynamics of belantamab mafodotin (antibody-drug 
conjugate, including complex with soluble BCMA (sBCMA)) and total monoclonal 
antibody (total mAb; including complex), and cys-mcMMAF were investigated in 291 
participants with RRMM following IV administration at doses from 0.03 to 4.6 mg/kg 
Q3W in Study BMA117159 (n=73) and at doses of 2.5 or 3.4 mg/kg Q3W in Study 
205678 (n=218). 
Maximum concentrations (Cmax) of belantamab mafodotin and total monoclonal 
antibody were observed at or shortly after the end of infusion (EOI), while cys-mcMMAF 
Cmax values were generally observed on Day 2. On a molar basis, plasma concentrations 
of cys-mcMMAF were <1% of belantamab mafodotin concentrations. There was limited 
accumulation (less than 2-fold) of belantamab mafodotin or cys-mcMMAF during 
subsequent cycles.  
Belantamab mafodotin pharmacokinetics were well described by a linear, 
two-compartment population model, with a time-varying decrease in clearance in a 
population pharmacokinetic analysis. At Cycle 1, belantamab mafodotin had a systemic 
clearance of 0.92 L/day, steady-state volume of distribution of 10.8 L, and an elimination 
half-life of 12 days in participants with RRMM in Study 205678. Over time, clearance 
was reduced by 28%, resulting in an elimination half-life of 14 days. The time to 50% 
change in clearance was approximately 50 days.  
No clinically significant differences in the pharmacokinetics of belantamab mafodotin or 
cys-mcMMAF were observed based on age (34 to 89 years), sex, race (African 
American/Black and White), body weight (42 to 130 kg), mild or moderate renal 
impairment (eGFR≥30 mL/min/1.73m2) or mild hepatic impairment (NCI-ODWG 
classification). Higher serum levels of 2-microglobulin, IgG, and soluble BCMA 
(sBCMA) and lower levels of albumin are associated with more advanced multiple 
myeloma or a higher multiple myeloma disease burden. Higher baseline IgG and sBCMA 
levels, and lower baseline albumin levels were associated with higher belantamab 
mafodotin clearance leading to lower average and trough concentrations (Ctau) of 
belantamab mafodotin. Higher baseline IgG and sBCMA levels were associated with 
higher cys-mcMMAF central volume of distribution leading to lower cys-mcMMAF 
Cmax.  
In nonclinical studies, cys-mcMMAF had limited metabolic clearance. In vitro data 
suggested that belantamab mafodotin and cys-mcMMAF are unlikely to perpetrate a 
drug-drug interaction or to be a victim of a drug-drug interaction with inhibitors or 
inducers of cytochromes (CYP) P450. Cys-mcMMAF was an in vitro substrate of organic 
anion transporting polypeptides (OATP)1B1 and OATP1B3, multidrug resistance 
associated proteins (MRP)1, MRP2, and MRP3, a borderline substrate of bile salt export 
pump (BSEP), and a possible substrate of P-glycoprotein (P-gp). Following the 
administration of belantamab mafodotin to participants with RRMM, only intact 
cys-mcMMAF was detected in pooled human urine, with no evidence of other 
MMAF-related urinary metabolites.  


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Free sBCMA levels were measured in Study BMA117159 and Study 205678. All 
participants exhibited reductions in free sBCMA concentration at end of infusion 
compared to baseline at Cycle 1, with a return to near-baseline level by seven days after 
dosing, reflecting binding of belantamab mafodotin to sBCMA. Maximum decreases 
ranged from 2% to 97%, which were qualitatively dose-dependent, with larger reductions 
in free sBCMA at higher doses.  
Exposure-response analyses performed for Study 205678 and/or Study BMA117159 
found that ocular safety endpoints were most strongly associated with belantamab 
mafodotin exposure, while efficacy endpoints had a weaker association with belantamab 
mafodotin exposure. Both safety and efficacy endpoints were associated with patient 
characteristics. Belantamab mafodotin Ctau was associated with probability of corneal 
events and keratopathy and cys-mcMMAF Cmax was associated with probability of 
thrombocytopenia. Probability of occurrence of dry eye, blurred vision, neutropenia and 
infusion related reaction were not associated with an exposure measure. In addition, the 
results of the analysis of concentration against corrected QT interval (QTc) demonstrated 
that belantamab mafodotin or cys-mcMMAF did not have a significant effect on cardiac 
repolarization. 
Additional information related to belantamab clinical PK, PD, and exposure-response 
relationships can be found in the Investigator’s Brochure [GSK2857916 IB, 
GlaxoSmithKline Document Number 2013N175128_09, 2021] 
2.5. 
Benefit / Risk Assessment 
2.5.1. 
Risk Assessment 
Additional information about the known and expected benefits and risks, detailed 
information of nonclinical and clinical findings information regarding warnings, 
precautions, contraindications, adverse events, and other pertinent information on 
belantamab mafodotin that may impact participant eligibility is provided in the 
Investigator’s Brochure [GSK2857916 (IB) GlaxoSmithKline Document Number 
2013N175128_09, 2021]. 
Table 5 
Risk Assessment and Mitigation Strategy 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Investigational Product (Belantamab Mafodotin) 
Corneal events  
Reversible corneal events have been 
observed with various ADCs (specific 
corneal changes with ADCs conjugated to 
MMAF). 
Cornea-related AEs such as blurred vision, 
dry/watery eyes, decreased visual acuity, 
and photophobia are among the most 
common AEs associated with belantamab 
mafodotin in the clinic. Corneal erosions 
and corneal ulcers (associated with 
infective keratitis) have also been reported. 
Active monitoring for corneal events 
according to the Schedule of Activities 
(Table 1).  
 
 
Timely evaluation and management by 
an ophthalmologist (an optometrist if an 
ophthalmologist is not available) upon 
developing corneal related events. 
Recommendations for dose 


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


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


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


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
 
Impaired Male Fertility 
In animal studies, belantamab 
mafodotin treatment has resulted in 
testicular toxicity and adverse effects on 
spermatogenesis. Reversibility of testicular 
toxicity is unknown at this time. 
Men will be advised to have sperm 
samples frozen and stored before 
treatment. 
See contraception requirements in 
Section 11.5 
Risks from Study Procedures 
Bone marrow 
aspiration/biopsy 
Pain, infection, bleeding may occur after 
the procedure 
Participants will be treated according to 
institution’s practice 
Incidental findings 
during image 
acquisition: 
During the acquisition of imaging data 
(e.g., MRI, CT, PET, ECHO), non-MM 
disease or drug related clinically relevant 
abnormalities could be found by the 
radiographer or echocardiographer 
performing the exams. 
Copies of all medical images that include 
non-disease, clinically relevant 
abnormalities will be shared with the site 
for storage 
TCR = T-cell receptor; mAb = Monoclonal antibody; AEs = Adverse Events 
2.5.2. 
Benefit Assessment 
Belantamab mafodotin has demonstrated strong single-agent activity in 2 clinical studies 
conducted in heavily pre-treated participants with RRMM (Q3W schedule via IV 
administration). Based on the available data for the FTIH study BMA117159, as of the 
efficacy cut-off of 31 August 2018, participants receiving belantamab mafodotin at 
3.4 mg/kg had an ORR of 60% (95% CI: 42.1, 76.1) and a median PFS of 12.0 (95% CI: 
3.1, NR) in a heavily pre-treated population (57% ≥5 prior lines of therapy) [Trudel, 
2019; Trudel, 2018]. For participants refractory to both immunomodulators and 
proteasome inhibitors (N=32), the confirmed overall response rate was 56% (95% CI: 
37.7%, 73.6%). In 205678/ DREAMM 2, both dose levels evaluated, 2.5 and 3.4 mg/kg, 
had a positive benefit/risk profile [Li, 2017; Lonial, 2020].  
Based on this profile, it is reasonable to hypothesize that the use of belantamab mafodotin 
as a single agent will provide an improved benefit compared to the combination regimen 
of pom/dex in this patient population. 
2.5.3. 
Overall Benefit-Risk Conclusions 
Taking into account the measures to minimize risks to participants in this study, the 
potential risks identified in association with belantamab mafodotin are justified by the 
anticipated benefits that may be afforded to participants with RRMM. 
3. 
OBJECTIVES AND ENDPOINTS 
The purpose of this Phase II study is to evaluate the safety and efficacy of belantamab 
mafodotin in participants with RRMM who have received at least 3 prior lines of anti-
myeloma therapy, have failed an anti-CD38 antibody, and are refractory to PI and 


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immunomodulatory agents. See Table 6 for the primary, secondary, exploratory, and 
other objectives, along with the corresponding endpoints.  
Table 6 
Objectives and Endpoints for Study 205678 - Belantamab Mafodotin 
in RRMM Participants Previously Treated with an Anti-CD38 
Antibody 
Objectives 
Endpoints 
Primary Objective 
To evaluate the clinical efficacy of 2 doses 
of belantamab mafodotin in participants 
with relapsed/refractory multiple myeloma.  
ORR, defined as the percentage of participants with a confirmed 
partial response (PR) or better (i.e., PR, very good partial response 
[VGPR], complete response [CR] and stringent complete response 
[sCR]), according to the 2016 International Myeloma Working Group 
(IMWG) Response Criteria by Independent Review Committee (IRC). 
Secondary Objectives 
To further evaluate the clinical measures of 
efficacy of belantamab mafodotin in 
participants with RRMM 
 
 
ORR, defined as the percentage of participants with a confirmed 
partial response (PR) or better, according to the 2016 International 
Myeloma Working Group (IMWG) Response Criteria by investigator 
assessment. 
 
Clinical benefit rate (CBR), defined as the percentage of participants 
with a confirmed minimal response (MR) or better according to the 
2016 International Myeloma Working Group (IMWG) Response 
Criteria). 
 
Duration of response (DoR), defined as: the time from first 
documented evidence of PR or better until the earliest date of 
documented disease progression (PD) per IMWG; or death due to 
PD occurs among participants who achieve an overall response, i.e., 
confirmed PR or better. 
 
Time to response, defined as the time between the date of 
randomization and the first documented evidence of response (PR or 
better). 
 
Progression-free survival, defined as the time from randomization 
until the earliest date of documented disease progression (PD) per 
IMWG, or death due to any cause. 
 
Time to progression, defined as the time from randomization until the 
earliest date of documented PD per IMWG, or death due to PD. 
 
Overall survival, defined as the time from randomization until death 
due to any cause. 
To evaluate the safety of belantamab 
mafodotin in participants with RRMM. 
The safety profile of belantamab mafodotin will be evaluated in 
participants with RRMM as assessed through: 
standard clinical and laboratory tests (hematology and chemistry, 
physical examination, vital sign measurements, and diagnostic tests) 
through the collection of adverse events (AEs) and serious adverse 
events (SAEs) 
AEs of special interest 
ocular findings on ophthalmic exam 
To evaluate the pharmacokinetic profile of 
belantamab mafodotin 
Plasma concentrations of belantamab mafodotin (ADC, total mAb, 
and cys-mcMMAF) 
Derived pharmacokinetic parameter values (e.g., AUC, Cmax, tmax, 
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Objectives 
Endpoints 
To assess anti-drug antibodies (ADAs) 
against belantamab mafodotin 
Incidence and titers of ADAs against belantamab mafodotin 
Participant self-reported symptomatic 
adverse effects by evaluation of tolerability 
of belantamab mafodotin 
Symptomatic adverse effects and related impacts as measured by 
the PRO-CTCAE, NEI-VFQ-25 and OSDI 
To evaluate disease and treatment related 
symptoms and impact on function and 
health-related quality-of-life 
Health-related quality-of-life as measured by the EORTC QLQ-C30 
and EORTC QLQ-MY20 
Exploratory Objectives 
To explore the relationship between clinical 
response and other biologic characteristics 
including BCMA expression on tumor cells 
and sBCMA concentrations  
Determine BCMA expression levels and other markers on malignant 
cells, serum sBCMA levels, and evaluate the relationship of these 
factors to clinical response 
To investigate the relationship between 
genetic variants in the host and response 
to belantamab mafodotin  
Possible relationship between host genetic variation and response to 
belantamab mafodotin 
To evaluate disease and treatment related 
symptoms and impact on function and 
health-related quality-of-life 
Qualitative telephone interview(s) 
To explore exposure-response 
relationships between belantamab 
mafodotin exposure and clinical endpoints 
Explore relationships between belantamab mafodotin exposure (e.g., 
dose, dose intensity, concentration, Cmax, or AUC) and clinical 
endpoints (e.g., response, corneal event), if data permit 
To assess Minimal Residual Disease 
(MRD) in participants who achieve ≥VGPR 
or better 
Minimal Residual Disease (MRD) negativity rate, defined as: the 
percentage of participants who are MRD negative by Next 
Generation Sequencing (NGS). 
To assess the safety, efficacy, 
immunogenicity, and pharmacokinetics of 
belantamab mafodotin in a lyophilized 
configuration (approximately 25 
participants) 
AEs, clinical and laboratory assessments; descriptive analyses of 
ORR, duration of response, time to response, time to progression, 
overall response; incidence and titers against belantamab mafodotin; 
plasma concentrations of belantamab mafodotin (ADC, total mAb, 
and cys-mcMMAF) and derived pharmacokinetic parameters, if data 
permit 
Ocular sub-study objective 
To evaluate the effect of topical 
corticosteroids on corneal findings in 
approximately 30 participants who will 
receive monocular topical corticosteroids 
for the first 4 cycles 
Description of differences in corneal findings in each eye based on 
ophthalmic examinations (participant-level). 
Abbreviations: IV = intravenous; Q3W: once every 3 weeks; RRMM = relapsed refractory multiple myeloma; BCMA = 
B-cell maturation antigen; MMAF = monomethyl auristatin-F; MRD = minimal residual disease; NGS = Next Generation 
Sequencing; ORR = overall response rate; CI = confidence interval; CR = complete response; VGPR = very good 
partial response; PR = partial response; PFS = progression free survival; AUC = area under the curve; Cmax = 
maximum concentration; tmax = time to maximum; t½ = half-life; PRO-CTCAE = Patient Reported Outcomes-Common 
Terminology Criteria for Adverse Events; NEI-VFQ-25 = National Eye Institute Visual Functioning Questionnaire 25; 
OSDI = Ocular Surface Disease Index; EORTC = European Organisation for Research and Treatment of Cancer; 
QLQ-C30 = Quality of Life Questionnaire 30-item Core module; FLC = free light chain; SCT = stem cell transplant; 
QLQ-MY20 = ; Quality of Life Questionnaire 20-item module for MM; QTcF = QT interval corrected by Fridericia's 
formula; HIV = human immune deficiency virus; RNA = ribose nucleic acid. 
 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
This is a Phase II, open-label, two-arm, randomized, multicenter study to evaluate the 
efficacy and safety of belantamab mafodotin monotherapy at the dose of 2.5 mg/kg or 3.4 


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


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


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


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If the 3.4 mg/kg dose is discontinued, participants who are currently treated at this 
dose will have the option to switch to 2.5 mg/kg:  
• 
In cases when the participant has not achieved a maximum benefit of CR or sCR, did 
not experience toxicity requiring a dose reduction, and is willing to continue at the 
higher dose level, the participant will have the option to stay on their original dose 
upon signing an additional informed consent informing them that a lower dose level 
has been selected for the remaining participants.  
The final analysis of the primary endpoint (ORR) will be performed 6 months after the 
last participant is randomized. The study will continue and participants will remain on 
treatment and continue to be followed.  
For participants who discontinue study treatment for reasons other than PD, disease 
evaluations will continue to be performed at 3-week intervals until confirmed PD, death, 
start of a new anticancer treatment, withdrawal of consent, or end of the study whichever 
occurs first. After PD is documented, participants will be followed for survival and 
subsequent anticancer therapy every 3 months until study ends.  
Pharmacokinetic samples will be collected from all participants. The collection of PK 
samples for determination of belantamab mafodotin plasma (ADC and total antibody) 
and cys-mcMMAF concentrations will allow characterization of the PK profile and 
support investigation of its pharmacology. 
Genetic testing (in consenting participants) and biomarker research samples will also be 
conducted on samples from all participants prior to the first dose. Patient-Reported 
Outcomes (PRO) data will be collected at each clinic visit. 
Protocol waivers or exemptions are not allowed. Therefore, adherence to the study design 
requirements, including those specified in the SOA (Table 1 to Table 4) is essential. 
Following 39 months post LSFD, a Post Analysis Continued Treatment (PACT) will be 
implemented. The study 205678 (DREAMM-2) will be closed. At this time, the 
collection of data for all recruited participants who no longer receive study treatment will 
stop entirely and 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 and only SAEs, overdose and pregnancy cases, and pre-specified ocular data will be 
reported directly to GSK. 
Supplementary study conduct information not mandated to be present in this protocol is 
provided in the accompanying Study Reference Manual (SRM). The SRM will provide 
the site personnel with administrative and detailed technical information that does not 
affect participant safety. 
4.2. 
Number of Participants 
Approximately 170 participants were initially planned to be screened to enroll a 
minimum of 155 participants at approximately 60 investigational sites globally. A 
minimum of 130 participants (65/arm) were planned to be enrolled to 2 arms receiving 


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frozen liquid solution of belantamab mafodotin which includes ~30 participants from the 
ocular sub-study. Approximately 200 participants will be enrolled in the frozen liquid 
portion of the study. Approximately twenty-five additional participants will be enrolled 
into the independent lyophilized drug product cohort. 
4.3. 
Participant Completion 
A participant will be considered to have completed the study if he or she has received at 
least one dose of the study treatment and is in follow-up, or has died when the study is 
closed, and has not withdrawn consent from study participation.  
4.4. 
Scientific Rationale for Study Design 
Patients with RRMM who have relapsed after prior treatment with an anti-CD38 antibody 
and are refractory to a PI and an immunomodulatory agent represent a population of 
unmet medical need, for whom there is no approved treatment option. Given the clinical 
activity demonstrated in the BMA117159 study, treatment with belantamab mafodotin 
may offer a benefit to this patient population. It is also expected that due to its unique 
mechanism of action, belantamab mafodotin may be able to overcome the resistance to 
previously used drugs in the MM population.  
Belantamab mafodotin is the first-in-class ADC targeting BCMA. Preliminary clinical 
data for belantamab mafodotin monotherapy from Study BMA117159 among 35 
participants indicate an ORR of 60% [95% CI: 42.1%, 76.1%], with 51% of participants 
(n=18) having deep responses of VGPR or better. The median DoR has not been 
achieved, the 25th percentile for DoR is 6.7 months; the median PFS in this population 
was 7.9 months [95% CI: 3.1, NA]. Of note, the ORR for participants previously treated 
with daratumumab (n=14) was 43% (95% CI: 17.7, -71.1). Fifty nine percent of the 
treated population had 5 of more prior treatments.  
The response rate observed in this population is higher than response rates observed in 
similarly defined patient populations treated with other recently approved drugs (ORR 
ranging from 23.7% to 33.1% for Carfilzomib, pomalidomide and daratumumab) [Siegel, 
2012; Usmani, 2016; Kumar, 2008]. Given the evidence of clinical activity and 
manageable safety/tolerability profile demonstrated to date, the current evidence supports 
further development. 
The two-arm design with two dose levels and a futility analysis is justified for this 
population because there is no approved comparator for the proposed treatment setting. In 
Study BMA117159, the maximum clinical benefit (ORR) was observed at the 3.4 mg/kg 
dose level, but a significant number of participants required dose delays and dose 
reductions. At lower dose levels, the results were variable, with wide confidence 
intervals. In order to generate additional safety and efficacy data at a lower dose while 
providing participants a chance of deriving clinical benefit, the dose of 2.5 mg/kg has 
been selected for additional testing (see Section 4.5 for dose justification). 
This design is appropriate for the selected patient population, since there is no approved 
standard of care in patients failing daratumumab. As shown in earlier studies on a similar 
population, the response rate is low and the mPFS is short in those patients. For example, 


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


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


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


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Table 8 
Summary of Predicted Mean Response and Mean ≥Grade 2 Corneal 
Event* and 95% Credible Intervals (Parts 1 and 2, Study BMA117159) 
Dose (mg/kg) 
Predicted response rate (%) 
(95% credible interval) 
Predicted G2 corneal AE rate (%) 
(95% credible interval) 
1.92 
25.3 (9.4, 42.2) 
33.7 (18.3, 49.0) 
2.5 
37.0 (22.3, 51.6) 
43.4 (30.2, 56.9) 
3.4 
53.7 (40.3, 66.9) 
55.7 (42.3, 68.7) 
*Predicted values are based on the posterior distribution of response rate and corneal event rate per CTCAE 4.03 
 
In summary, based on the safety, tolerability, and clinical activity observed to date, 
2.5 mg/kg and 3.4 mg/kg were selected as the appropriate dose levels of belantamab 
mafodotin to be further studied in this phase 2 study. The dose may be further 
individually adjusted in participants experiencing adverse events, according to the 
guidance in the protocol.  
Overall, there were no new safety signals identified in the 205678 study, and the profile 
of adverse events was similar to the experience in BMA117159 for both arms. The dose 
of 2.5 mg/kg appears to have a lower incidence of adverse events and less frequent dose 
delays and reductions, and it results in similar efficacy with 3.4 mg/kg dose as measured 
by ORR.  
In summary, the selection of the dose of 2.5 mg/kg Q3W for future single agent studies 
with belantamab mafodotin is based on the available data with single agent belantamab 
mafodotin in heavily pretreated patients with relapsed/refractory MM from 2 studies: 
BMA117159 and 205678, which showed clinically meaningful efficacy with a 
manageable safety profile in a heavily pre-treated patient population. 
4.6. 
End of Study Definition 
The study will end when all participants have either died, progressed, withdrawn consent, 
or have been followed for a minimum of 39 months from the LSFD. 
 
Following 39 months post LSFD, PACT will be implemented and the study 205678 
(DREAMM-2) will be closed. At this time, the collection of data for all recruited 
participants who no longer receive study treatment will stop entirely and clinical trial 
database will be closed. Those participants still benefiting from study drug will continue 
to receive study drug and only SAEs, overdose and pregnancy cases, and pre-specified 
ocular data will be reported directly to GSK. 
At this time point, (3 weeks post data cut-off the clinical study database will be closed to 
new data. Participants who are receiving belantamab mafodotin may continue to receive 
belantamab mafodotin if they are gaining clinical benefit as assessed by the investigator 
or can choose to discontinue belantamab mafodotin.  
 
Dispensing of study treatment following 39 months post LSFD, will utilize a manual 
resupply option, and drug accountability assessment will be performed at the site. All 
participants will be monitored and receive follow-up care in accordance with standard 


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local clinical practice. For participants who do continue to receive belantamab mafodotin 
beyond the time of the final data cut-off, investigators will continue to report all SAEs, 
pregnancy and overdose cases up to 70 days after last dose of study treatment, and pre-
specified ocular data (see SRM) will be reported until resolution unless the event is 
considered by the investigator to be unlikely to resolve, or the patient is lost to follow up. 
Additionally, any SAE and pre-specified ocular event that are ongoing at the time of this 
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. 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. 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, are not permitted.  
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
1. Provide signed written informed consent, which includes compliance with the 
requirements and restrictions listed in the consent form 
2. Male or female, 18 years or older (at the time consent is obtained)  
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (Appendix 
8) 
4. Histologically or cytologically confirmed diagnosis of MM as defined according to 
IMWG, [Rajkumar, 2014] criteria, and  
 
a) Has undergone stem cell transplant or is considered transplant ineligible, and 
  
b) Has failed at least 3 prior lines of anti-myeloma treatments, including an anti-
CD38 antibody (e.g., daratumumab) alone or in combination, and is refractory to 
an immunomodulatory agent (i.e., lenalidomide or pomalidomide), and to a 
proteasome inhibitor (e.g., bortezomib, ixazomib or carfilzomib). The number of 
prior lines of therapy will be determined according to the guidelines in 
Rajkumar, 2015. 
 
Refractory myeloma is defined as disease that is nonresponsive while on 
primary or salvage therapy, or progresses within 60 days of last therapy. 
Nonresponsive disease is defined as either failure to achieve at least minimal 
response or development of progressive disease (PD) while on therapy 
[Rajkumar, 2011] 
5. Has measurable disease with at least one of the following: 
a. 
Serum M-protein 0.5 g/dL (5 g/L) 


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b. Urine M-protein 200 mg/24h 
c. 
Serum FLC assay: Involved FLC level 10 mg/dL (100 mg/L) and an 
abnormal serum free light chain ratio (<0.26 or >1.65) 
6. Participants with a history of autologous stem cell transplant are eligible for study 
participation provided the following eligibility criteria are met: 
a. 
transplant was >100 days prior to study enrolment 
b. no active infection(s) 
c. 
participant meets the remainder of the eligibility criteria outlined in this protocol 
7. Adequate organ system functions as defined in Table 9. 
Table 9 
Criteria for Determining Adequate Organ System Function  
System 
Laboratory Values 
Hematologic 
Absolute neutrophil count (ANC) 
1.0 X 109/L 
Hemoglobin 
8.0 g/dL 
Platelets 
50 X 109/L 
Hepatic 
 
Total bilirubin 
≤1.5X ULN  
(Isolated bilirubin ≥1.5xULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%) 
ALT 
2.5 X ULN 
Renal 
eGFRa 
Spot urine (albumin/creatinine ratios (spot urine) 
30 mL/min/ 1.73 m2  
<500 mg/g (56 mg/mmol) 
Cardiac 
LVEF (Echo) 
45% 
a. 
As calculated MDRD equation (Appendix 10) 
Note: Laboratory results obtained during Screening must be used to determine eligibility criteria. In situations 
where laboratory results are outside the permitted range, the investigator may retest the participant and the 
subsequent within range screening result may be used to confirm eligibility. 
 
8. Female Participants: Contraceptive use by men or women should be consistent with 
local regulations regarding the methods of contraception for those participating in 
clinical studies.  
 
A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and at least one of the following conditions applies: 
• 
Is not a woman of childbearing potential (WOCBP) 
 
OR 
• 
Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of <1% per year), preferably with low user dependency, during the 
intervention period and for at least 80 days after the last dose of study 
intervention and agrees not to donate eggs (ova, oocytes) for the purpose of 
reproduction during this period. The investigator should evaluate the 
effectiveness of the contraceptive method in relationship to the first dose of 


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study intervention. 
 
A WOCBP must have a negative highly sensitive serum pregnancy test (as 
required by local regulations) within 72 hours before the first dose of study 
intervention.  
 
The investigator is responsible for review of medical history, menstrual history, 
and recent sexual activity to decrease the risk for inclusion of a woman with an 
early undetected pregnancy. 
9. Male Participants: Contraceptive use by men or women should be consistent with 
local regulations regarding the methods of contraception for those participating in 
clinical studies.  
 
Male participants are eligible to participate if they agree to the following during the 
intervention period and for at least 140 days:  
• 
Refrain from donating sperm 
 
PLUS either: 
• 
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long term and persistent basis) and agree to remain abstinent.  
 
OR 
• 
Must agree to use contraception/barrier as detailed below: 
 
Agree to use a male condom and female partner to use an additional highly 
effective contraceptive method with a failure rate of <1% per year as when 
having sexual intercourse with a woman of childbearing potential who is not 
currently pregnant.  
10. All prior treatment-related toxicities (defined by National Cancer Institute- Common 
Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03, must be ≤Grade 1 
at the time of enrolment except for alopecia and Grade 2 peripheral neuropathy. 
11. (France only) A participant will be eligible for inclusion in this study only if either 
affiliated to or a beneficiary of a social security category. 
 
5.2. 
Exclusion Criteria 
Participants satisfying any of these criteria are not eligible for assignment to treatment: 
1. Systemic anti-myeloma therapy within ≤14 days or 5 half-lives, whichever is 
shorter, or plasmapheresis within 7 days prior to the first dose of study drug 
2. Systemic treatment with high dose steroids (equivalent to 60 mg prednisone 
daily for ≥4 days) within the past 14 days if administered to treat MM or non- 
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3. Symptomatic amyloidosis, active ‘polyneuropathy, organomegaly, 
endocrinopathy, myeloma protein, and skin changes’ (POEMS) syndrome, 
active plasma cell leukemia at the time of screening.  
4. Prior allogeneic stem cell transplant 
5. Current corneal epithelial disease except mild punctate keratopathy  
6. Use of an investigational drug within 14 days or five half-lives, whichever is 
shorter, preceding the first dose of study drug. Prior treatment with a 
monoclonal antibody within 30 days of receiving the first dose of study drugs. 
Prior BCMA targeted therapy.  
7. Evidence of active mucosal or internal bleeding 
8. Any major surgery within the last four weeks 
9. Presence of active renal condition (infection, requirement for dialysis or any 
other condition that could affect participant’s safety). Participants with isolated 
proteinuria resulting from MM are eligible, provided they fulfil criteria given in 
Table 9. 
10. Any serious and/or unstable pre-existing medical, psychiatric disorder or other 
conditions (including lab abnormalities) that could interfere with participant’s 
safety, obtaining informed consent or compliance to the study procedures.  
11. Current unstable liver or biliary disease per investigator assessment defined by 
the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, 
esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable 
chronic liver disease (including Gilbert’s syndrome or asymptomatic gallstones) 
or hepatobiliary involvement of malignancy is acceptable if participant 
otherwise meets entry criteria. 
12.  Malignancies other than disease under study are excluded, except for any other 
malignancy from which the participant has been disease-free for more than 2 
years and, in the opinion of the principal investigators and GSK Medical 
Monitor, will not affect the evaluation of the effects of this clinical trial treatment 
on the currently targeted malignancy (MM). Participants with curatively treated 
non-melanoma skin cancer may be enrolled. 
13. Evidence of cardiovascular risk including any of the following: 
a. 
QTcF interval QTcF > 480 msec (the QT interval values must be corrected 
for heart rate by Fridericia’s formula [QTcF]) 
b. Evidence of current clinically significant uncontrolled arrhythmias, 
including clinically significant ECG abnormalities such as 2nd degree 
(Type II) or 3rd degree atrioventricular (AV) block. 
c. 
History of myocardial infarction, acute coronary syndromes (including 
unstable angina), coronary angioplasty, or stenting or bypass grafting within 
six months of Screening. 
d. Class III or IV heart failure as defined by the New York Heart Association 
functional classification system [NYHA, 1994] 


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e. 
Uncontrolled hypertension 
14. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs 
chemically related to belantamab mafodotin, or any of the components of the 
study treatment. 
15. Pregnant or lactating female. 
16. Active infection requiring antibiotic, antiviral, or antifungal treatment. 
17. Known HIV infection. 
18. Presence of hepatitis B surface antigen (HBsAg), or hepatitis B core antibody 
(HBcAb at screening or within 3 months prior to first dose of study treatment 
19. Positive hepatitis C antibody test result or positive hepatitis C RNA test result at 
screening or within 3 months prior to first dose of study treatment.  
Note: Participants with positive Hepatitis C antibody due to prior resolved 
disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is 
obtained. 
Note: Hepatitis RNA testing is optional and participants with negative Hepatitis 
C antibody test are not required to also undergo Hepatitis C RNA testing. 
 
5.3. 
Lifestyle Restrictions 
Contact lenses are prohibited while the participant is on study. 
5.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently enrolled. A minimal set of screen failure information is required 
to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to 
queries from regulatory authorities. Minimal information to be entered into INFORM 
includes demography, screen failure details, eligibility criteria, and any serious adverse 
events (SAEs). 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened. Rescreened participants must be assigned a new unique participant 
number that is different from the initial number. 
6. 
TREATMENTS 
Study treatment is defined as any investigational treatment intended to be administered to 
a study participant according to the study protocol. Belantamab mafodotin will be 
administered intravenously.  
Belantamab mafodotin will be administered intravenously, at the study sites, as either 2.5 
mg/kg or 3.4 mg/kg calculated dose.  


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Product name: 
Belantamab mafodotin  
Dosage form: 
Frozen liquid, 30 mg/vial solution in single-use vial 
or  
Lyophilized powder, 100 mg/vial in single-use vial for reconstitution 
(independent cohort with approximately 25 participants) 
Unit dose strength(s)/Dose 
Level(s): 
30 mg/vial / 2.5 or 3.4 mg/kg (Frozen liquid)  
or  
100 mg/vial / 2.5 or 3.4 mg/kg (Lyophilized powder) 
Route of Administration 
Delivered as IV solution over at least 30 minutes*.  
Dosing instructions: 
Dilute belantamab mafodotin in normal 0.9% saline to the appropriate 
concentration for the dose. Doses of belantamab mafodotin are to be 
administered as an IV infusion via an infusion pump. See Investigator’s 
Brochure for compatible administration materials. 
 
For lyophilized powder only: Reconstitute belantamab mafodotin lyophilized 
powder 100 mg/vial 2.0mL of water for injection (WFI); dilute with saline 
before use.  
Manufacturer/ Source of 
Procurement: 
GSK/Baxter 
*Infusions may be prolonged in the event of an infusion reaction. If multiple participants experience clinically significant 
infusion reactions, the infusion rate may be slowed for all future administrations of study treatment(s) for all 
participants. Should this global change in infusion rate be required, it will be communicated to the sites in writing. 
6.1. 
Belantamab Mafodotin Treatments Administered 
Belantamab mafodotin is to be administered at a calculated dose of 2.5 mg/kg or 3.4 
mg/kg as an IV infusion, via an infusion pump. Administration of belantamab mafodotin 
will be documented in the clinic source documents and reported in the electronic case 
report form (eCRF). The time of start and end of infusion will be documented in eCRF. 
Belantamab mafodotin will be administered on Day 1 of each cycle. Premedication is not 
required prior to infusion unless deemed medically necessary by the investigator, in 
which case it should be administered according to institutional recommendations.  
Any participant experiencing an IRR must receive appropriate medical treatment. When 
the participant’s condition is stable, the infusion may be restarted at a slower rate. For 
details on restarting the belantamab mafodotin infusion after interruption for IRR, please 
see Table 11. 
In general, upon restarting, the infusion rate must be decreased by half at the time the 
infusion was interrupted.  
Participants will be treated until disease progression, or until death, or until unacceptable 
toxicity (including but not restricted to meeting stopping criteria as outlined in Section 
7.1).  
6.2. 
Dose Modification 
Dose modifications will be managed according to Dose Reduction Criteria and Guidance 
provided in Table 11 and Table 12. 


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6.2.1. 
Adjustments Due to Body Weight 
The actual body weight in kg at baseline (assessed on Cycle 1 Day 1 prior to dosing) will 
be used for dose calculation of belantamab mafodotin in all participants during the 
treatment period. However, if the change of body weight is greater than 10%, the dose 
must be recalculated based on the actual body weight at the time of dosing.  
6.2.2. 
Dose Reductions for Toxicity 
After Cycle 1, participants may have their dose delayed or reduced for toxicities 
according to the recommendations.  
See Table 11 for dose modifications guidelines for belantamab mafodotin for specific 
toxicity related AEs and Table 12 for guidelines for drug-related toxicities, not otherwise 
specified AEs.  
See Table 13 for dose modification guidelines for cornea-related AEs associated with 
belantamab mafodotin.  
Permitted dose reductions for belantamab mafodotin are shown in Table 10. 
Table 10 
Permitted Dose Reductions 
Starting dose 
1st reduction 
2nd reduction 
3.4 mg/kg 
2.5 mg/kg 
1.92 mg/kg 
2.5 mg/kg 
1.92 mg/kg 
-- 
 
• 
If the participant cannot tolerate the drug after the allowed dose reductions, he or 
she must be withdrawn from the study for lack of tolerability. 
• 
Only 1 dose reduction (to 1.92 mg/kg) is permitted for the lower starting dose of 
2.5 mg/kg. 
• 
In case of full resolution of symptoms which lead to dose reduction, further 
treatment at the previous dose may be considered by the investigator.  
Dosing delays are permitted in the case of medical/surgical events or for logistical 
reasons not related to study therapy (e.g., elective surgery, unrelated medical events, 
participant vacation, and/or holidays, but not for participants’ decision to delay 
treatment). If a dose is delayed, the participant should wait for the next scheduled dose to 
resume treatment. In individual cases where in the judgement of an investigator waiting a 
full cycle to resume treatment after delay (skipping dose) related to toxicity which has 
resolved would be detrimental to patient’s health- the Principal Investigator should 
contact Medical Monitor to discuss an earlier re-start. An earlier re-start may be 
considered only for patients who have recovered from toxicity to at least G1 or less. The 
dosing with belantamab mafodotin cannot occur more frequently than every 21 days ( 3-
day window). In such cases efficacy and safety assessments must continue to be 
conducted every 3 weeks in line with initial efficacy and safety assessments on study, 
which may result in 2 separate visits (1 for dosing, 1 for disease assessments) (Table 2).  


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Evaluations associated with a Dose (Table 2) would be entered into the eCRF under the 
next scheduled cycle.  
The reason for any dose delay must be documented in the participant's eCRF and clinic 
record. 
Resuming treatment with belantamab mafodotin will be possible with or without dose 
reduction after the toxicity has resolved to Grade 1 or less.  
Table 11 
Dose Modification Guidelines for Belantamab Mafodotin-Related 
Adverse Events 
Toxicity 
Grade/description 
of toxicity 
Recommendations for belantamab mafodotin 
Elevated serum creatinine 
which cannot be explained by 
concomitant sepsis, TLS, other 
severe condition with fever, or 
dehydration 
If absolute serum 
creatinine 
increases from 
baseline by >0.5 
mg/dL 
• 
Repeat serum creatinine within 48 hours 
• 
If confirmed: withhold therapy, institute treatment and 
monitoring as clinically indicated, and follow for 
resolution 
• 
Discuss any further dosing with Medical Monitora 
Serum creatinine >Grade 3 
>3.0 mg/dL from 
baseline 
or 
3.0-6.0xULN 
• 
Provide appropriate medical treatment. 
• 
Permanently discontinue treatment with belantamab 
mafodotin  
Spot urine (albumin / 
creatinine ratios) 
>2000 mg/g 
(or 224 mg/mmol) 
• 
Re-test (at least 7 days apart). 
• 
If not confirmed, continue belantamab mafodotin at 
100% dose 
• 
If confirmed on re-test and no clear evidence of 
disease progression 
o 
Interrupt treatment with belantamab mafodotin 
o 
Repeat testing within 4 weeks 
i. 
If spot urine <2000 mg/g (224 mg/mmol), 
may restart belantamab mafodotin with a 
dose reduction 
ii. 
If spot urine remains >2000 mg/g 
(224 mg/mmol) after 4 weeks, 
permanently discontinue belantamab 
mafodotin and withdraw participant from 
study; provide treatment as clinically 
indicated and follow for resolutiona 
Thrombocytopenia (on days of 
dosing  
3 or 4 
• 
Withhold treatment until thrombocytopenia recovered 
to Grade 2 or less (≤G2). 
• 
If Grade 3-4 thrombocytopenia is considered disease-
related, treatment may be continued with more 
frequent hematology monitoring, until recovery to 
Grade 2 or less. Dose reduction should be 
considered in those patients 
• 
Implement supportive treatment (e.g. transfusion) as 
clinically indicated and per local practice. 
Febrile neutropenia 
 Defined as: single 
temp of 38.3oC, or 
sustained 38oC for 
>1 hr. AND ANC 
<1.0 x 109/L  
• 
Withhold belantamab mafodotin and immediately 
hospitalize participant with appropriate management, 
per local institutional guidance. 
• 
Consider additional supportive treatment per local 
practice (e.g. growth factors). 


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


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Table 12 
General Dose Modification and Management Guidelines for Drug- 
related Adverse Events Not Otherwise Specifieda 
Severity 
Management 
Follow-up 
Grade 1 
• 
Administer symptomatic 
treatment as appropriate 
• 
Continue study drug(s)a 
Provide close follow-up to evaluate for increased severity, no 
dose modification necessary 
Grade 2 
• 
Administer symptomatic 
treatment 
• 
Investigate etiology 
• 
Consider consulting 
subspecialist, and/or 
diagnostic procedure 
Symptoms resolved in ≤7 days: 
Continue after resolution at the current dose 
Symptoms ongoing >7 days or worsening: 
o Delay study drugb, or consider dose reduction by 25% 
If recovery takes >3 weeks- consult GSK MM  
• 
If symptoms continue or worsen to Grade 3-4, see below 
Grade 3 
• 
Provide appropriate medical 
treatment  
• 
Consider Consulting 
subspecialist 
Delay treatment till recovery to G1 or less. Consider dose 
reduction. Consider consultation with GSK MM. 
Exceptions: Participants who develop G3 toxicities which 
respond to standard treatment and resolve to ≤G1 within 48 
hours may continue treatment at scheduled or reduced dose  
Grade 4 
• 
Provide appropriate medical 
treatment  
• 
Consider Consulting 
subspecialist 
• 
Discuss with Sponsor/Medical 
Monitor 
Interrupt treatment. Further treatment with belantamab 
mafodotin only allowed on individual basis if in the discussion 
with MM it is agreed that benefits outweigh the risks for a given 
participant 
a. 
Treatment-related decisions can be made based on local laboratory results if central results are not available or 
delayed. 
b. 
In case a dose is delayed, the participant should wait for the next scheduled dose to resume treatment. 
 
 


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


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


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


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


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Participants will receive study treatment at the site directly from the investigator or 
designee, under medical supervision. The date and time of each dose administered in the 
clinic will be recorded in the source documents and reported in the eCRF. The dose of 
study treatment and study participant identification will be confirmed at the time of 
dosing by a member of the study site staff other than the person administering the study 
treatment and documented in source.  
6.7. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrolment or receives during the study must be recorded along with: 
• 
reason for use 
• 
dates of administration including start and end dates 
• 
dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
Participants will be instructed to inform the investigator prior to starting any new 
medications from the time of first dose of study treatment until the end of the study (Final 
Study Visit). Any concomitant medication(s), including non-prescription medication(s) 
and herbal product(s), taken during the study will be recorded in the electronic case 
report form (eCRF). Additionally, a complete list of all prior anti-cancer therapies will be 
recorded in the eCRF. 
If future changes are made to the list of permitted/prohibited medications, formal 
documentation will be provided by GSK and stored in the study file. The SRM will be 
updated to include this information. Any such changes will be communicated to the 
investigative sites in the form of a letter. 
6.7.1. 
Permitted Medication(s) 
Participants should receive full supportive care during the study, including transfusions of 
blood products, growth factors, and treatment with antibiotics, anti-emetics, antidiarrheal, 
and analgesics, as appropriate. Concomitant therapy with bisphosphonates is allowed. 
Participants may receive local irradiation for pain or stability control.  
6.7.2. 
Prohibited Medication(s) 
Chronic treatment with oral steroids is prohibited while the participant is on study, unless 
for treatment of acute complications related to study treatment, or pre-medication prior to 
belantamab mafodotin infusion. Steroids may be used to treat infusion-related reactions. 
Inhaled steroids are allowed for management of asthma or COPD exacerbations. Chronic 
low dose replacement therapy (less than or equal to 10 mg prednisolone) is allowed in 
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Elimination pathways for belantamab mafodotin and cys-mcMMAF have not been 
characterized in humans. Cys-mcMMAF was not an inhibitor, an inducer, or a good 
substrate of cytochrome P450 enzymes in vitro. Cys-mcMMAF was shown to be a 
substrate of P-glycoprotein (P-gp) and Organic Anion Transporting Proteins (OATP) 1B1 
and 1B3 transporters in vitro. Caution should be exercised when belantamab mafodotin is 
combined with strong inhibitors of P-gp, and strong inhibitors of OATP1B1 and 
OATP1B3 should be avoided unless considered medically necessary. See the SRM for 
more information. 
Other prohibited therapies include: 
• 
Plasmapheresis: prohibited from 7 days prior to first dose through the end of 
study.  
• 
Any other anti-cancer therapy not specified in this protocol, and any 
investigational agents other than belantamab mafodotin. 
6.7.3. 
Prohibited Device(s) 
Contact lenses are prohibited while the participant is on study. 
6.8. 
Treatment after the End of the Study 
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the participant’s medical condition.  
Refer to Section 8 and the SOA (Table 3) for follow-up assessments of participants who 
are to be followed for disease progression and survival after they permanently 
discontinue from study treatment.  
6.9. 
Continued Access to Study Intervention after the End of the 
Study 
Participants receiving belantamab mafodotin following 39 months post LSFD, at the time 
of study completion may continue to receive belantamab mafodotin, if in the opinion of 
their treating physician, they are continuing to derive clinical benefit from continued 
treatment. Study treatment will continue until a study discontinuation (see Protocol 
Section 7) as assessed by the investigator has been met. Investigators will report all 
SAEs, overdose and pregnancy cases until 70 days after receipt of their last dose of study 
treatment and pre-specified ocular data (see SRM) will be reported until resolution unless 
the event is considered by the investigator to be unlikely to resolve, or the patient is lost 
to follow up. Post EOS, data cut-off, recording and follow up of SAEs and pre-specified 
ocular data will be done via paper forms. Drug accountability data will also be collected 
at site. Assessments will revert to standard of care at their particular site. 


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7. 
DISCONTINUATION CRITERIA 
7.1. 
Discontinuation of Study Treatment 
Participants will receive study treatment until disease progression, unacceptable toxicity, 
or death (including but not restricted to meeting stopping criteria for significant toxicity 
as outlined in Section 7.1).  
Study treatment may be permanently discontinued for any of the following reasons: 
• 
disease progression or unacceptable toxicity. 
• 
participant has met any of the protocol defined safety stopping criteria 
(Section 6.2). 
• 
deviation(s) from the protocol 
• 
request of the participant or proxy (withdrawal of consent by participant or 
proxy) 
• 
investigator’s discretion 
• 
concurrent illness that prevents further administration of study treatment(s) 
• 
pregnancy  
• 
participant is lost to follow-up  
• 
study is closed or terminated 
The primary reason study treatment was permanently discontinued must be documented 
in the participant’s medical records and electronic case report form (eCRF)  
If the participant voluntarily discontinues from treatment due to toxicity, AE (adverse 
event) must be recorded as the primary reason for permanently discontinuation on the 
eCRF.  
Once a participant has permanently discontinued from study treatment, the participant 
will not be allowed to re-enter the study. 
All participants who discontinue from study treatment for any reason other than 
confirmed progression or death will complete safety assessments, and will be followed up 
for PFS, OS, and subsequent anti-cancer therapy after study as specified in the SOA 
(Table 1).  
PFS Follow-up: 
All participants who permanently discontinue study treatment in the absence of disease 
progression will remain in the study and will be followed for progression according to the 
protocol schedule until: 
• 
New anti-cancer therapy is initiated 
• 
Progression is documented, or  


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• 
Death occurs 
 
OS Follow-up: 
All participants who permanently discontinue study treatment will be followed for 
survival and new anti-cancer therapy until the end of study as described in Section 4.3.  
Withdrawal from Study Treatment: 
A participant may withdraw from study treatment at any time at his/her own request or 
may be withdrawn at any time at the discretion of the investigator for safety, behavioral 
or administrative reasons. If a participant withdraws from the study, he/she may request 
destruction of any samples taken, and the investigator must document this in the site 
study records.  
7.2. 
Safety Stopping Criteria 
7.2.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event. The diagram below illustrates Liver 
Stopping Event Algorithm (Figure 3)  
Figure 3 
Liver Chemistry Stopping Criteria – Liver Stopping Event Algorithm 
 
The details on follow up procedures are outlined in Appendix 7. 


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7.2.2. 
Study Treatment Restart or Rechallenge 
If participant meets liver chemistry stopping criteria do not restart/rechallenge participant 
with study treatment unless: 
• 
GSK Medical Governance approval is granted (as described below), 
• 
Ethics and/or IRB approval is obtained, if required, and 
• 
Separate consent for treatment restart/rechallenge is signed by the participant 
If GSK Medical Governance approval to restart/rechallenge participant with study 
treatment is not granted, then participant must permanently discontinue study treatment 
and may continue in the study for protocol-specified follow up assessments. 
7.2.3. 
Left Ventricular Ejection Fraction (LVEF) Stopping Criteria 
Echocardiography must be performed at Screening. If an ECHO is done at any point 
during the study, the following stopping criteria are to be employed. Participants who 
have an asymptomatic absolute decrease of >10% in LVEF and the ejection fraction is 
below the institution’s lower limit of normal (LLN) should temporarily discontinue study 
treatment and have a repeat evaluation of LVEF within 1 week. Echocardiogram (ECHO) 
should be repeated every 1 to 2 weeks for 4 weeks or until LVEF recovery to above 
institutional LLN and within 10% of baseline.  
• 
If the LVEF recovers (defined as  institutional LLN and absolute decrease 
10% compared with baseline) at any time during the next 4 weeks, after 
consultation with and approval from the GSK medical monitor, the participant 
may be restarted on belantamab mafodotin at a reduced dose. For such 
participants, monitoring of LVEF will be performed 2 and 4 weeks after re-
challenge, then every 4 weeks for a total of 16 weeks. 
• 
If repeat LVEF does not recover within 4 weeks, treatment must be permanently 
discontinued. Ejection fraction must be monitored every 4 weeks for a total of 
16 weeks or until resolution (whichever occurs first). 
Participants with Grade 3 or 4 (symptomatic) left ventricular systolic dysfunction must 
interrupt treatment with belantamab mafodotin. Ejection fraction must be monitored 
every 4 weeks for a total of 16 weeks or until resolution. If recovery occurs (LVEF  
institutional LLN and symptom resolution) within 4 weeks, then treatment with 
belantamab mafodotin may be restarted at a reduced dose in consultation with the 
medical monitor. 
7.2.4. 
Corneal Event Stopping Criteria 
All belantamab mafodotin dose modifications and stopping criteria are to be based on the 
GS/KVA Scale for treatment related corneal toxicities (Appendix 9). Corneal events will 
be graded according to both CTCAE criteria for eye disorders (see Section 8.2) and the 
guidelines provided in Appendix 9. The treating physician or ophthalmologist (or 
optometrist, if an ophthalmologist is not available) must discuss the participants who 
develop a Grade 4 corneal event according to the GSK/KVA scale with the GSK Medical 


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Monitor or a GSK ophthalmologist to determine whether the participant can be allowed 
to restart treatment with belantamab mafodotin or whether belantamab mafodotin should 
be permanently discontinued. The decision will be documented in study files, together 
with individual assessment of risk-benefit. For details on re-start guidance (Table 13). 
7.2.5. 
Infusion-Related Reaction Management and Stopping Criteria 
Premedication is not required prior to infusion unless deemed medically appropriate by 
the investigator following evaluation of infusion related reactions. Premedication should 
be considered in any participant who experienced an infusion related reaction at first or 
any subsequent infusion with belantamab mafodotin. 
IRRs should be managed by guidelines provided in Table 11. A participant that 
experiences a Grade 4 IRR should be permanently withdrawn from the study. 
7.2.6. 
Allergic and Anaphylactic Reaction Stopping Criteria 
All participants will be monitored carefully for evidence of allergic response. A 
participant that exhibits signs or symptoms of severe hypersensitivity or anaphylaxis will 
receive appropriate medical treatment and be permanently withdrawn from the study 
treatment.  
7.3. 
Withdrawal from the Study 
• 
A participant may withdraw from the study at any time at his/her own request, 
or may be withdrawn at any time at the discretion of the investigator for safety, 
behavioral, compliance or administrative reasons. 
• 
If the participant withdraws consent for disclosure of future information, the 
sponsor may retain and continue to use any data collected before such a 
withdrawal of consent. 
• 
If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the investigator must document this in the site 
study records. 
• 
Refer to the SOA for data to be collected at the time of study discontinuation 
follow-up and for any further evaluations that need to be completed. 
 
7.4. 
Lost to Follow Up 
The following actions must be taken in relation to a participant who fails to attend the 
clinic for a required study visit: 
• 
The site must attempt to contact the participant and re-schedule the missed visit 
as soon as possible.  
• 
The site must counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to 


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continue or if the investigator believes that the participant should continue in the 
study.  
• 
In cases where the participant is deemed ‘lost to follow up’, the investigator or 
designee must make every effort to regain contact with the participant (where 
possible, 3 telephone calls and if necessary a certified letter to the participant’s 
last known mailing address or local equivalent methods). These contact attempts 
should be documented in the participant’s medical record.  
• 
Should the participant continue to be unreachable, only then will he/she be 
considered to have withdrawn from the study with a primary reason of “Lost to 
Follow-up.”  
 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
A signed, written informed consent form must be obtained from the participant prior to 
any study-specific procedures or assessments being performed. The timing of each 
assessment is listed in the Schedule of Activities (Table 1).  
A list of clinical laboratory tests is displayed in Table 14. 
Whenever vital signs, and blood draws are scheduled for the same nominal time, it is 
recommended that the assessments occur in the following order: vital signs, followed by 
the blood draws. The timing of the assessments must allow the blood draw to occur at the 
exact nominal time. Detailed procedures for obtaining each assessment are provided in 
the SRM. 
• 
Study procedures and their timing are summarized in the SOA (Table 1 – Table 
3).  
• 
Protocol waivers or exemptions are not allowed.  
• 
Demographic and baseline assessments will include year of birth, sex, race, and 
ethnicity. 
• 
Medical/medication/family history will be assessed as related to the 
inclusion/exclusion criteria listed in Section 5.1 and Section 5.2. 
• 
Immediate safety concerns must be discussed with the sponsor immediately 
upon occurrence or awareness to determine if the participant should continue or 
discontinue study treatment. 
• 
Adherence to the study design requirements, including those specified in the 
SOA, is essential and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that 
potential participants meet all eligibility criteria. The investigator will maintain a 
screening log to record details of all participants screened and to confirm 
eligibility or record reasons for screening failure, as applicable.  
• 
Procedures conducted as part of the participant’s routine clinical management 
(e.g., blood count) and obtained before signing of ICF may be utilized for 


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screening or baseline purposes provided the procedure met the protocol-
specified criteria and was performed within the time frame defined in the SOA. 
• 
Survival follow-up can be conducted by phone call.  
• 
Baseline disease assessments must be completed with 21 days prior to dosing 
start unless otherwise specified. Refer to SOA.  
• 
Screening assessments performed within the permitted time do not need to be 
repeated on C1D1 unless otherwise specified. 
• 
Safety labs completed within 72 hours of first dose do not need to be repeated 
on C1D1. 
• 
Pregnancy testing must be completed within 72 hours prior to first dose. 
• 
ECHO must be completed within 35 days prior to first dose. 
• 
Imaging must be completed within 30 days prior to first dose. 
• 
On-study visits have a ±3-day window 
• 
PFS follow-up visits have a ±7-day window. 
• 
Survival follow-up visits have a ±14-day window. 
 


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


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


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• 
Bone marrow (aspirate preferred) at screening and to confirm CR. Additional 
BM testing for MRD testing in case of VGPR or CR is achieved, and BM biopsy 
for immunohistochemistry (IHC) to confirm sCR.  
• 
Imaging of extramedullary disease (in participants with extramedullary disease) 
• 
Germany: Only MRI is allowed to be used as imaging modality for 
participants with extramedullary disease. 
• 
PET/CT is required upon achieving CR or sCR  
• 
Germany: no PET/CT to confirm CR or sCR will be performed until approval 
by the German Federal Office for Radiation Protection until further notice.  
• 
Skeletal surveys at screening  
• 
Germany: Only MRI is allowed to be used as imaging modality of bones for 
lytic lesions. 
Response evaluation will be performed according to the IMWG Uniform Response 
Criteria for Multiple Myeloma [Kumar, 2016]. 
Baseline serum/urine disease assessment will be completed during screening period 
(within 21 days prior to the first dose of study treatment) and baseline imaging within 30 
days prior to the first dose of study treatment. On study serum and urine based 
assessments (M-protein, FLC, immunofixation) will be performed every 3 weeks. Details 
for the preparation and shipment of samples for central laboratory assessments will be 
provided in the SRM. 
In participants with extramedullary myeloma, the disease assessments must include 
imaging (e.g., CT, MRI, or PET-CT scans- the same method should be used throughout 
the study) and physical examination (as indicated for palpable/superficial lesions).  
For participants who are followed by imaging for extramedullary disease the imaging 
must be performed as described in the SOA (Section 1.2).  
All assessments on study must be performed on a calendar schedule and must not be 
affected by dose interruptions/delays. For post-baseline assessments, a window of 
3 days is permitted to allow for flexible scheduling.  
For participants who are discontinuing IP due to PD the confirmation of laboratory 
parameters must be performed from a different blood collection performed either on the 
same day, or within 14 days of the original date of suspected disease progression, 
preferably before initiation of any new anti-myeloma therapy. For participants with PD 
due to extramedullary disease, confirmatory scans are not required. The laboratory 
parameters do not need to be repeated only if the extramedullary disease is the single site 
of progression. The assessments may be performed during End of Treatment Visit (Table 
3) for the Schedule of Activities of anti-cancer activity  
If the last imaging assessment was greater than or equal to 8 weeks prior to the 
participant’s discontinuation from study treatment and progressive disease has not been 


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documented, a new disease assessment must be obtained at the time of discontinuation 
from study treatment. 
8.1.1. 
Independent Review Committee 
An Independent Review Committee (IRC) will be utilized to assess efficacy endpoints of 
the study. All laboratory parameters and lesion measurements used to assess participant 
response will be shared with the IRC. Additional information can be found in Appendix 3 
and in the IRC Charter.  
8.2. 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 4. 
Adverse events will be coded using the standard MedDRA and grouped by system organ 
class. Adverse events will be graded by the investigator according to the NCI-CTCAE, 
(version 4.03). Corneal events associated with belantamab mafodotin will also be graded 
according to the GSK/KVA scale provided in Appendix 9. Dose modifications as a result 
of corneal events will be based on the GSK/KVA scale for corneal events (Table 22).  
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study treatment or the study, 
or that caused the participant to discontinue the study treatment (see Section 7). 
8.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information  
• 
All SAEs will be collected from the start of treatment until 45 days following 
discontinuation of study treatment regardless of initiation of a new cancer therapy or 
transfer to hospice at the time points specified in the SOA (Table 1, Table 2, and 
Table 3). However, any SAEs assessed as related to study participation (e.g., study 
treatment, protocol-mandated procedures, invasive tests, or change in existing 
therapy) or related to a GSK product will be recorded from the time a participant 
consents to participate in the study up to and including any follow-up. 
• 
All AEs will be collected from the start of treatment until 45 days following 
discontinuation of study treatment regardless of initiation of a new cancer therapy or 
transfer to hospice at the time points specified in the SOA. 
• 
Medical occurrences that begin before the start of study treatment but after obtaining 
informed consent will be recorded on the Medical History/Current Medical 
Conditions section of the electronic case report form (eCRF) not the AE section. 
• 
All SAEs will be recorded and reported to the sponsor or designee immediately and 
under no circumstance should this exceed 24 hours, as indicated in Appendix 4. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it 
being available. 
• 
Investigators are not obligated to actively seek AEs or SAEs in former study 
participants. However, if the investigator learns of any SAE, including a death, at 


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any time after a participant has been discharged from the study, and he/she considers 
the event to be reasonably related to the study treatment or study participation, the 
investigator must promptly notify the sponsor. 
• 
The method of recording, evaluating, and assessing causality of AEs and SAEs and 
the procedures for completing and transmitting SAE reports are provided in 
Appendix 4. 
• 
Investigator need not update tick-box in InForm to confirm review of the causality 
assessment for the SAE within 72 hours. It is enough to record the same in source 
notes. 
• 
Following 39 months post LSFD, participants still deriving clinical benefit in the 
opinion of their treating physician may continue to receive belantamab mafodotin. 
For these participants, GSK will continue to collect safety information including 
SAEs, overdose and pregnancy cases and pre-specified ocular data via paper forms 
which will be reported directly to GSK. For these participants, SAEs, overdose and 
pregnancy cases will be reported during the treatment period and for up to 70 days 
after last dose and pre-specified ocular data will be reported until resolution unless 
the event is considered by the investigator to be unlikely to resolve, or the patient is 
lost to follow up. 
 
8.2.2. 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrence.  
8.2.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, and non-serious AEs of clinical 
interest, will be followed until the event is resolved, stabilized, otherwise explained, or 
the participant is lost to follow-up (as defined in Section 7.4). Further information on 
follow-up procedures is given in Appendix 4. 
8.2.4. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of 
a study treatment under clinical investigation are met.  
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study treatment under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, Institutional Review Boards 
(IRB)/Independent Ethics Committees (IEC), and investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 


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An investigator who receives an investigator safety report describing a SAE or other 
specific safety information e.g., summary or listing of SAE) from the sponsor will review 
and then file it along with the Investigator’s Brochure and will notify the IRB/IEC, if 
appropriate according to local requirements. 
8.2.5. 
Cardiovascular and Death Events 
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
For any cardiovascular events detailed in Appendix 4 and all deaths, whether or not they 
are considered SAEs, specific Cardiovascular (CV) and Death sections of the eCRF will 
be required to be completed. These sections include questions regarding cardiovascular 
(including sudden cardiac death) and non-cardiovascular death.  
The CV eCRFs are presented as queries in response to reporting of certain CV MedDRA 
terms. The CV information must be recorded in the specific cardiovascular section of the 
eCRF within one week of receipt of a CV Event data query prompting its completion. 
8.2.6. 
Disease-Related Events and/or Disease-Related  
Disease progression does not need to be reported as a serious adverse event (SAE). Death 
due to disease under study is to be recorded on the Death electronic case report form 
(eCRF). However, if the underlying disease (i.e., progression) is greater than that which 
would normally be expected for the participant, or if the investigator considers that there 
was a causal relationship between treatment with study treatment(s) or protocol design or 
procedures and the disease progression, then this must be reported as a SAE. 
8.2.7. 
Adverse Events of Special Interest 
Adverse events of special interest (AESI) for belantamab mafodotin are corneal events, 
thrombocytopenia and infusion related reactions. The severity of all AESI will be graded 
utilizing the National Cancer Institute- Common Toxicity Criteria for Adverse Events. 
Severity of corneal events will also be graded using the GSK/KVA scale for corneal 
events provided in Table 22. Guidelines for dose modifications and interruptions for 
management of common toxicities associated with the study treatment(s) are provided in 
Table 11. Dose modifications for belantamab mafodotin corneal events will be based on 
the GSK/KVA scale for corneal events in Table 22. 
8.2.8. 
Pregnancy 
Do not collect pregnancy information for female participants known to be pregnant 
during the screening phase or before exposure to study. 
The need for a screening pregnancy test depends on whether a female participant is of 
childbearing potential or non-childbearing potential. 
If a female participant is of childbearing potential, she must have a serum β-human 
chorionic gonadotropin (β –HCG) pregnancy test performed within 72 hours prior to the 


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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 for female partners of male participants will be collected 
after the start of study treatment to 6 months following last dose of study treatment.  
• 
If a pregnancy is reported, the investigator must inform GSK within 24 hours of 
learning of the pregnancy and must follow the procedures outlined in Appendix 5. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, and ectopic pregnancy) are considered SAE. 
8.2.9. 
Ocular Examinations and Procedures 
A full baseline ophthalmic examination for all participants must include, but is not 
limited to: 
1. Best corrected visual acuity  
2. Documentation of manifest refraction used to obtain best corrected visual acuity 
3. Current glasses prescription (if applicable) 
4. Pupillary exam 
5. Extraocular muscle movements (graded from one to four with (+) sign 
indicating over action, (-) sign indicating under action and 0 representing normal 
movements 
6. Tear film examination: Schirmer’s test with anesthesia and tear breakup time  
7. Intraocular pressure measurement & time checked 
8. Full anterior segment examination including fluorescein staining of the cornea: 
9. Anterior segment exam (slit lamp) includes: orbit/lids/adnexa, conjunctiva, 
sclera, cornea, anterior chamber, iris, lens and anterior vitreous 
10. Anterior segment photography of a fluorescein stained cornea 
11. Dilated funduscopic exam: fundus photography with interpretation. 
12. Pachymetry  
The on treatment and follow-up ophthalmic exam must include everything except: dilated 
funduscopic exam /, including fundus photography, anterior segment photography, 
extraocular muscle movements, (which must be performed as clinically indicated) and 
current glasses prescription (if applicable). The last follow-up ophthalmic visit should 
also include anterior segment photography of a fluorescein stained cornea. Representative 
images will be collected and maintained at the investigator site as source data. 
The end of study treatment visit ophthalmic exam should match the baseline (screening) 
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Additional examinations should be performed at the discretion of the treating eye 
specialist.  
8.2.10. 
Ocular Sub-Study Examinations 
Refer to Table 4 for the schedule of assessments for ocular sub-study of participants 
Although ocular corticosteroids have been used in both published studies (Tannir, 2014; 
Moskowitz, 2015; Thompson, 2015; Reardon, 2016; Macsai, 2016) and BMA117159 to 
ameliorate the frequency and severity of MMAF-associated corneal events, this has yet to 
be investigated systematically. Furthermore, the effect of MMAF-conjugated ADCs on 
the eye has not been fully delineated in studies to date. Therefore, Study 205678 will 
include a sub-study of approximately 30 participants (~15 participants each dose) to 
evaluate the effect of ophthalmic topical corticosteroids on belantamab mafodotin-
associated corneal findings and to further characterize these findings. This sub-study of 
participants will be recruited at selected investigational sites associated with 
ophthalmologists with subspecialty training/expertise in the cornea. These participants 
will undergo additional ophthalmic examinations during the first 4 cycles of treatment at 
a minimum or as clinically indicated as determined by the treating ophthalmologist. A 
separate informed consent (in addition to the main study ICF) will be obtained from these 
participants. 
8.2.10.1. 
Monocular prophylaxis 
Figure 4 summarizes the prophylaxis administration schedule in the ocular sub-study of 
participants. 
The treating ophthalmologist, but not the participant, will be blinded as to which eye has 
received the prophylactic steroid treatment. 
Randomization will be done within each treatment arm centrally using a randomization 
schedule, which will assign participants in a 1:1 ratio to: 
• 
receive topical corticosteroids in right eye only 
• 
receive topical corticosteroids in left eye only. 
The participants of the sub-study will administer prophylactic corticosteroid eye drops 
(prednisolone acetate 1%, prednisolone phosphate 1%, dexamethasone 0.1%, or 
equivalent, 1 drop four times daily starting one day prior to dosing for a total of 7 days). 
They will be instructed to administer the steroid drops in only one eye. *** Based on data 
from the primary analysis the use of prophylactic steroid eye drops is no longer required 
for the main study participants. Determination for use of steroid eye drops will be up to 
the discretion of the treating ophthalmologist for the ocular sub-study participants.  
Corticosteroid treated eye 
• Participant should administer 1 drop of topical corticosteroid followed by 1 drop of 
preservative-free artificial tears 5-10 minutes later, four times daily. This should start 
one day prior to dosing for a total of 7 days.  


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


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After Cycle 4, monocular steroid treatment will be performed at the discretion of the 
treating ophthalmologist 
Based on data from the primary analysis the use of prophylactic steroid eye drops is no 
longer required for the main study participants. Determination for use of steroid eye 
drops will be up to the discretion of the treating ophthalmologist for the ocular sub-study 
participants.  
8.2.10.3. 
Sub-Study Exams 
Participants will be assessed by the treating ophthalmologist at baseline, every 3 weeks or 
prior to each dose, and on Day 10 of Cycles 1, 2, 3, and 4. After Cycle 4, the Day 10 
exam may be omitted.  
In addition to the full ophthalmic exam (Section 8.2.9), the participants at these selected 
sites will undergo the following additional studies during screening (baseline), at the first 
instance of corneal changes attributable to belantamab mafodotin, end of study treatment 
visit, last follow-up visit and as clinically indicated by the treating ophthalmologist:  
1. Anterior segment OCT (optical coherence tomography)  
2. Anterior segment/corneal slit lamp photography  
3. 
Confocal microscopy (if available at the site) 
4. 
Lissamine green staining 
 
Given that these evaluations are exploratory, the treating ophthalmologist has the 
discretion to perform them more frequently as they believe appropriate for the optimal 
care of the individual participant. Representative images will be collected and maintained 
at the investigator site as source data. 
8.3. 
Treatment of Overdose 
There is no specific antidote for an overdose of belantamab mafodotin. GSK does not 
recommend a specific treatment for an overdose of belantamab mafodotin. 
In the event of an overdose of belantamab mafodotin, the investigator must: 
• 
contact the GSK Medical Monitor immediately 
• 
monitor the participant closely for AEs/ SAEs and laboratory abnormalities until 
they have resolved and belantamab mafodotin concentrations are predicted to be 
within the anticipated range in absence of the overdose. 
8.4. 
Safety Assessments 
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8.4.1. 
Physical Examinations 
At screening, on dosing days, and at end of study treatment visit a full physical 
examination will include assessments of the head, eyes, ears, nose, throat, skin, thyroid, 
lungs, cardiovascular, abdomen (liver and spleen), lymph nodes, and extremities. Height 
(once at screening only) and weight must also be measured and recorded. 
8.4.2. 
ECOG Performance Status 
Participant performance status will be assessed at Screening, every 3 weeks starting at 
Week 4 and End of Treatment using the Eastern Cooperative Oncology Group (ECOG) 
scale, provided in Appendix 8. 
8.4.3. 
Vital Signs 
Vital sign measurements must include systolic and diastolic blood pressure, temperature, 
and pulse rate. Vital signs must be measured after resting for at least 5 minutes. Vital 
signs must be measured more frequently if warranted by the clinical condition of the 
participant. On days where vital signs are measured multiple times, temperature does not 
need to be repeated unless clinically indicated. 
8.4.3.1. 
First Infusion 
Monitoring intervals: Vital signs must be monitored at designated time points related to 
drug infusion as specified in the Schedule of Activities (Section 1.2). In general, 
participants must also be monitored for at least 1 hour after the completion of the first 
infusion and may be discharged if considered clinically stable and all other study 
procedures have been completed.  
8.4.3.2. 
Subsequent Infusions 
Monitoring intervals: Vital signs must be monitored at designated time points related to 
drug infusion as specified in the Schedule of Activities (Section 1.2). Participants may be 
discharged after the infusion has been completed if considered clinically stable and all 
other study procedures have been completed.  
8.4.4. 
Echocardiogram 
Echocardiograms (ECHOs) must be performed at baseline to assess cardiac ejection 
fraction for the purpose of study eligibility, as specified in the SOA. The evaluation of 
the echocardiographer must include an evaluation for left ventricular ejection fraction 
(LVEF). If an ECHO is performed on study the results must be documented in the e-
CRF. 
8.4.5. 
Laboratory Assessments 
All protocol-required laboratory assessments, as defined in Table 14, must be performed 
according to the SOA (Section 1.2). Details for the preparation and shipment of samples 
for central laboratory assessments will be provided in the SRM. 


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The investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the CRF. The 
laboratory reports must be filed with the source documents. Clinically significant 
abnormal laboratory findings are those which are not associated with the underlying 
disease, unless judged by the investigator to be more severe than expected for the 
participant's condition. 
All laboratory tests with values that are significantly abnormal during participation in the 
study or within 45 days after the last dose of study treatment must be repeated until the 
values return to normal or baseline.  
If such values do not return to normal within a period judged reasonable by the 
investigator, the etiology must be identified and the sponsor notified. 
Hematology, clinical chemistry, urinalysis, and additional parameters to be tested are 
listed, with detailed instructions and timing, in the SRM. 
8.4.6. 
Patient-Reported Outcome Version of the Common Term Criteria 
for Adverse Events (PRO-CTCAE) 
The Patient-Reported Outcomes Version of the Common Terminology Criteria for 
Adverse Events (PRO-CTCAE) is a patient-reported outcome measure developed to 
evaluate symptomatic toxicity in patients on cancer clinical trials [Basch, 2014]. The 
PRO-CTCAE was designed to be used as a companion to the Common Terminology 
Criteria for Adverse Events (CTCAE), the standard lexicon for adverse event reporting in 
cancer trials. The PRO-CTCAE includes an item library of 124 items representing 78 
symptomatic toxicities drawn from the CTCAE. PRO-CTCAE provides a systematic yet 
flexible tool for descriptive reporting of symptomatic treatment side effects in cancer 
clinical trials. In the present study, a sub-study of items selected from the PRO-CTCAE 
Version 1.0 Item library will be administered. Participants who are not able to complete 
the questionnaire on their own and require assistance may have the interview conducted 
verbally or by telephone. The interview must be read to the participants verbatim, and 
participant responses must be recorded directly without any interpretation.  
The PRO-CTCAE will be administered to participants in different regions based on the 
availability of translated versions.  
 
8.4.7. 
Visual Function Questionnaires 
The impact of potential ocular toxicity on function and health-related quality-of-life will 
be assessed with the use of two visual function questionnaires, the NEI-VFQ-25 and 
OSDI. All participants will use the Self-Administered version of the questionnaires, 
unless their vision prevents them from being able to complete the questionnaire on their 
own. Participants who are not able to complete the questionnaire on their own and require 
assistance must use an Interviewer Administered format. If the Interviewer Administered 
format is being used, it must be read to the participants verbatim, and participant 
responses must be recorded directly without any interpretation. For any additional 


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


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total antibody) and cys-mcMMAF will be determined in plasma samples using the 
currently approved bioanalytical methodology. Raw data will be archived at the 
bioanalytical site (detailed in the SRM). 
Once the plasma has been analyzed for belantamab mafodotin (ADC and total antibody) 
and cys-mcMMAF, any remaining plasma may be analyzed for other compound-related 
metabolites and the results reported under a separate GSK PTS-BIB protocol. 
8.6. 
Immunogenicity  
Serum samples for the analysis of anti-belantamab mafodotin antibodies will be collected 
from all participants according to the SoA. Additionally, serum samples should be 
collected at the final visit from participants who discontinued study intervention or were 
withdrawn from the study. These samples will be tested by the sponsor or sponsor’s 
designee.  
Samples will be tested for anti-belantamab mafodotin antibodies using a tiered-testing 
scheme consisting of validated screening, confirmation, and titration assays. Briefly, all 
samples will be tested in the screening assay. Samples that screen positive are considered 
potentially positive and will be tested for specificity in a confirmation assay. Finally, titer 
values will be obtained for confirmed positive samples using a titration assay. The sample 
results (e.g., positive or negative) and titer values (positive samples only) will be 
reported. Samples that test positive for anti-belantamab mafodotin antibodies may be 
further characterized in a validated neutralizing antibody assay to determine the 
neutralizing activity of the antibodies.  
The detection and characterization of antibodies to belantamab mafodotin will be 
performed using validated assays. The anti-belantamab mafodotin antibody assay was 
designed to detect antibodies to belantamab mafodotin, the unconjugated monoclonal 
antibody, and the linker-payload portion of belantamab mafodotin. Additionally, plasma 
samples will be collected at the same time points (see SoA) as the immunogenicity 
samples and analyzed to determine the belantamab mafodotin and total monoclonal 
antibody plasma concentrations. The plasma concentration results will enable 
interpretation of the anti-drug antibody data. Anti-drug antibody samples will be disposed 
of three months after final approved results are provided to the Clinical Study Team or its 
designee or upon documented study termination. 
Details of sample preparation, storage, and analysis will be provided in the SRM.  
8.7. 
Translational Research 
See Section 8.9. 
8.8. 
Genetics 
Participation in this part of the study is optional and all enrolled participants will be given 
the opportunity to contribute samples. Participation may be declined without effect on 
medical care during the clinical study. Separate consent signature is required for 
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Information regarding genetic research is included in Appendix 6. In approving the 
clinical protocol, the IEC/IRB and, where required, the applicable regulatory agency, are 
also approving the genetic research described in Appendix 6 unless otherwise indicated. 
Where required by regulatory authorities, approval of the genetic assessments can occur 
after approval is obtained for the rest of the study. In that case, written approval will 
indicate that approval of the genetic assessments is being deferred and the study, except 
for genetic assessments, can be initiated. If genetic assessments are not approved, they 
will not be conducted. 
8.9. 
Tumor Biomarker Analysis 
8.9.1. 
sBCMA Sample Analysis 
The BCMA receptor undergoes gamma-secretase mediated cleavage, leading to release 
of the BCMA extracellular domain as soluble BCMA (sBCMA) into the circulation 
[Laurent, 2015]. 
Samples will be collected to measure concentrations of sBCMA at the time points 
specified in the SOA using a validated assay. Details of sample preparation, storage, and 
analysis will be provided in the SRM.  
Serum analysis for sBCMA will be performed under control of GSK PTS-BIB group, the 
details of which will be included in the SRM. Raw data will be archived at the 
bioanalytical site (detailed in the SRM). 
8.9.2. 
Potential Tumor Related Biomarkers 
While BCMA expression is present in multiple myeloma, there is some variability in its 
expression, as well as its membranous/cytosolic expression pattern. Therefore, it is 
important to determine if there is any association between the expression levels of 
BCMA on multiple myeloma cells and clinical responses.  
Additionally, any blood, serum, and bone marrow samples collected during this study 
may be used to measure novel biomarkers to identify factors associated with the 
biological and clinical responses to belantamab mafodotin. If relevant, this approach may 
be extended to include the identification of biomarkers associated with AEs. Unless 
stated otherwise, these investigations may be performed irrespective of whether a 
response to belantamab mafodotin is observed. 
Samples will be collected at the time points indicated in the SOA. The sample collection 
strategy may be adjusted on the basis of emerging data from this study or other studies 
involving belantamab mafodotin in order to ensure optimal evaluation of any potential 
biomarkers. Additionally, novel biomarkers may also be incorporated, as data warrants. 
These analyses may include but not be limited to: 
• 
Bone marrow BCMA expression by IHC performed on bone marrow aspirate 
• 
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• 
Soluble factors, including circulating plasma cell-free DNA (cfDNA). 
 
8.10. 
Evaluation of Anti-Cancer Activity 
Response will be assessed according to the IMWG criteria, [Kumar, 2016] by the 
Investigator and by an IRC. 
Standard disease assessments for MM will include serum and urine laboratory tests, bone 
marrow biopsy at the time of CR (IHC), and MRD testing at the time of VGPR, CR, and 
baseline. Evaluation will follow the guidance of International Myeloma Working Group 
(IMWG) Uniform Response Criteria for Multiple Myeloma 2016. 
• 
Clinical efficacy measured as Overall Response Rate (ORR), which is defined as the 
percentage of participants with confirmed stringent complete response (sCR), 
complete response (CR), very good partial response (VGPR), or partial response 
(PR) as assessed by 2016 recommendation of the IMWG Panel I [Kumar, 2016].  
• 
Other efficacy measures of interest (see Section 8.1)  
• 
The percentage of participants achieving MRD negativity. 
Disease assessment will include laboratory testing and physical examination (as indicated 
for palpable/superficial lesions), or imaging CT, MRI, PET CT, or X-ray (as indicated). 
Laboratory-based disease assessments will be completed within 21 days prior to the first 
dose of belantamab mafodotin then testing will be performed every 3 weeks from Cycle 1 
Day 1 (C1D1). The imaging will be performed up to 30 days prior to the first dose and 
will be repeated as indicated in the SOA table. See the SOA for the Schedule of 
Activities of anti-cancer activity.  
Assessments must be performed on a calendar schedule and must not be affected by dose 
interruptions/delays.  
MRD negativity rate (defined as the percentage of participants who are MRD negative by 
clonoSEQ). Testing will be performed at: Screen for all participants; and at the time of 
achieving VGPR or CR. The testing will be repeated 6 months and 12 months after 
achieving VGPR or CR. If MRD sample is drawn after date of achieving VGPR or CR 
the repeat testing should take place 6 months and 12 months from time of initial MRD 
testing  
8.11. 
Health-Related Quality-of-Life 
Three Health-Related Quality-of-Life (HRQoL) assessments will be performed in this 
study. More details about all patient questionnaires can be found in the SRM.  
The following assessments will be administered to participants in different regions based 
on the availability of translated versions. 


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8.11.1. 
European Organization for Research and Treatment of Cancer 
Quality of Life Questionnaire 30-item Core module (EORTC QLQ-
C30) 
The EORTC QLQ-C30 is a 30-item questionnaire containing both single- and multi-item 
measures [Aaronson, 1993]. These include five functional scales (Physical, Role, 
Cognitive, Emotional, and Social Functioning), three symptom scales (Fatigue, Pain, and 
Nausea/Vomiting), a Global Health Status/QoL scale, and six single items (Constipation, 
Diarrhea, Insomnia, Dyspnea, Appetite Loss, and Financial Difficulties). Scores for each 
scale and single-item measure are averaged and transformed linearly to a score ranging 
from 0–100. A high score for functional scales and for Global Health Status/QoL 
represent better functioning ability or HRQoL, whereas a high score for symptom scales 
and single items represents significant symptomatology [Proskorovsky, 2014]. 
8.11.2. 
European Organization for Research and Treatment of Cancer 
Quality of Life Questionnaire 20-item Multiple Myeloma module 
(EORTC QLQ-MY20) 
The EORTC QLQ-MY20 is a supplement to the QLQ-C30 instrument used in patients 
with multiple myeloma [Aaronson, 1993; Cocks, 2007]. The module comprises 20 
questions that address four myeloma-specific HRQoL domains: Disease Symptoms, Side 
Effects of Treatment, Future Perspective, and Body Image. Three of the four QLQ-MY20 
domains are multi-item scales: Disease Symptoms (includes bone aches or pain, back 
pain, hip pain, arm or shoulder pain, chest pain, and pain increasing with activity); Side 
Effects of Treatment (includes drowsiness, thirst, feeling ill, dry mouth, hair loss, upset 
by hair loss, tingling hands or feet, restlessness/agitation, acid indigestion/heartburn, and 
burning or sore eyes); and Future Perspective (includes worry about death and health in 
the future, and thinking about illness). The Body Image scale is a single-item scale that 
addresses physical attractiveness. As with the QLQ-C30, QLQ-MY20 domain scores are 
averaged and transformed linearly to a score ranging from 0–100. A high score for 
Disease Symptoms and Side Effects of Treatment represents a high level of 
symptomatology or problems, whereas a high score for Future Perspective and Body 
Image represents better outcomes [Proskorovsky, 2014]. 
8.11.3. 
Qualitative Telephone Interviews (Patient Interviews) 
To further evaluate disease and treatment related symptoms and associated impacts on 
function and health-related quality of life, participants will participate in qualitative 
interviews conducted via telephone. The interview will be conducted by a trained 
interviewer in the participant’s native language and will be audio recorded for 
transcription and analysis. 
The patient interview (PRO) should be conducted via telephone within 21(7 days) days 
following Day 1 of the fourth treatment cycle (C4D1). The PRO interview should also be 
conducted within 21 days (7 days) of the participants end of treatment visit, unless the 
participant has already completed their interview following C4D1 within the prior 30 
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9. 
STATISTICAL CONSIDERATIONS 
9.1. 
Hypothesis Testing 
This is a two-arm study. The primary objective of this study is to establish the efficacy of 
BCMA over historical control with respect to ORR for participants with RRMM for each 
of the two dose levels (frozen liquid solution) studied. 
The study is designed to provide evidence with respect to ORR to either support the null 
hypothesis, H0: ORR ≤15%, or reject H0 in favor of the alternative hypothesis, 
H1: ORR≥33%. The hypothesis testing will be performed within each arm separately. No 
hypothesis testing for comparing ORR between the two arms will be performed. 
All randomized participants will be included in the final analysis to test the hypotheses of 
interest regardless of length of follow-up or whether or not they receive the treatment or 
whether or not they have a post-baseline assessment (i.e., participants will not be 
replaced). 
An interim analysis (IA) will be conducted after approximately 25 randomized 
participants per arm are evaluable (i.e., received at least two doses of study treatment and 
have completed at least one disease assessment after the second dose, or progressed or 
died or discontinued treatment due to reasons other than PD).  
The Final analysis will be performed based on a data cutoff 6 months after the last 
participant (in the frozen liquid solution) is randomized in the study to allow sufficient 
data maturity of all efficacy endpoints. Time from first-subject-first visit (FSFV) to 
primary ORR analysis will be approximately 12 months. The timeline is subject to 
change based on the actual enrollment rate. 
An updated analysis for OS will be performed at end of study as defined in Section 4.3. 
9.2. 
Sample Size Determination 
The sample size calculation was initially performed using East 6.4 software as a starting 
point, based on the ORR comparison between the belantamab mafodotin arm and the 
historical control in order to choose a final refined study design. The following 
assumptions were made in the estimation of the required sample size: 
• 
Normal approximation of binomial proportion 
• 
A response rate of ≥33% in the BCMA arm and ≤15% for the historical control 
• 
A 1.25%, one-sided risk of erroneously claiming superiority of the BCMA arm, in 
the presence of no true underlying improvement 
• 
A ~90% chance of rejecting the null hypothesis when the alternative hypothesis is 
true 
An IA after approximately 38% of information is available (i.e., approximately after 25 
participants out of originally planned 65 participants per arm are evaluable for IA), with a 
futility rule based on a gamma spending function. 


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


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


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


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


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Table 18 
Statistical Analysis Methods for Safety Endpoints 
Endpoint 
Statistical Analysis Methods 
Secondary 
Adverse Events: All adverse events whether serious or non-serious, will be reported from the 
start of treatment until 45 days after the last dose of study treatment, until the participant 
withdraws consent for study participation, or until the participant starts subsequent anticancer 
therapy, whichever occurs first. AEs will be recorded using standard medical terminology and 
graded according to the NCI-CTCAE, Version 4.03. For AE reporting, the verbatim term used in 
the CRF by investigators to identify adverse events will be coded using the latest version of 
MedDRA coding dictionary [NCI, 2010]. 
 
Adverse events will be summarized by frequency and proportion of total participants, by system 
organ class and preferred term. Separate summaries will be given for all AEs, treatment-related 
AEs, SAEs, and AEs leading to discontinuation of study treatment. Adverse events, if listed in 
the NCI-CTCAE (version 4.03,) will be summarized by the maximum grade.  
 
Characteristics (e.g., number of occurrences, action taken, grade, etc.) of the following AEs of 
clinical interest will be summarized separately:  
• 
The incidence of deaths and the primary cause of death will be summarized. 
• 
Clinical Laboratory Evaluation: The evaluation of clinical laboratory tests will focus on 
selected laboratory analytes from the hematology and blood chemistry panel. 
• 
Descriptive statistics (mean, standard deviation, median, and range) will be used to 
summarize observed laboratory values and change from baseline in observed value 
at each scheduled visit or worst-case post baseline, as appropriate. 
• 
The worst-case- toxicity grade in hematology and chemistry result during the 
treatment will be summarized. 
• 
Corneal events associated with belantamab mafodotin will be summarized using the 
GSK/KVA scale 
 
Other Safety Measures: Data for vital signs, electrocardiograms (ECGs), echocardiograms 
(ECHOs), and ophthalmic examination findings will be summarized. For continuous variables, 
these summaries will include sample size, mean, median, standard deviation, minimum, and 
maximum. For categorical variables, the summaries will include frequencies and corresponding 
percentages. Further details will be provided in the Reporting and Analysis Plan (RAP). 
Exploratory 
Exploratory analyses will be described in the RAP 
 
9.5.3. 
Analyses of Health-Related Quality of Life Data 
Descriptive statistics will be used to summarize scores derived from different 
questionnaires and change from baseline at each scheduled visit. Additional details will 
be provided in the reporting and analysis plan. 
9.5.4. 
Pharmacokinetic Analyses 
9.5.4.1. 
Pharmacokinetic Data Analyses 
Concentration-Time Data: Linear and semi-logarithmic individual concentration-time 
profiles and mean and median profiles (when appropriate) will be plotted for belantamab 
mafodotin (ADC and total mAb) and cys-mcMMAF. Concentrations of belantamab 
mafodotin (ADC and total mAb) and cys-mcMMAF will be listed for each participant 
and summarized (when appropriate) by planned time point and dose level. 


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


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


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


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


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


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


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


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


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


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


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


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11.3. 
Appendix 3: Study Governance Considerations 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with: 
• Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines 
• Applicable ICH Good Clinical Practice (GCP) Guidelines 
• Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, Investigator Brochure, and other 
relevant documents (e.g., advertisements) must be submitted to an IRB/IEC by 
the investigator and reviewed and approved by the IRB/IEC before the study is 
initiated.  
• 
Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.  
• 
The investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/EC 
• Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures 
• Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European 
regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations 
Financial Disclosure 
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
Informed Consent Process 
• 
The investigator or his/her representative will explain the nature of the study to 
the participant or his/her legally authorized representative and answer all 
questions regarding the study.  


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• 
Participants must be informed that their participation is voluntary. Participants 
or their legally authorized representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center.  
• 
The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study.  
• 
A copy of the ICF(s) must be provided to the participant or the participant’s 
legally authorized representative.  
Data Protection 
• 
Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred.  
• 
The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant.  
• 
The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorized personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities. 
Committees Structure 
An IRC will be utilized to assess response and progression and primary endpoint of 
the study. Digital copies of all scans must be maintained at Investigator site as source 
document. Further details on the IRC process will be defined in the IRC charter 
Results from the IRC will not be provided to the investigative sites during the study.  
 
Participant data to be shared with the IRC may include the following: 
• Scans (CT, MRI, or PET CT- whichever applicable) 
• SPEP, UPEP, M-protein in 24 hr. urine collection immunoelectrophoresis- 
urine and serum, serum calcium, and albumin (unless reported as albumin 
corrected),  
• Serum kappa, serum lambda FLC, FLC Ratio 
• MRD results 


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Publication Policy 
• 
The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments.  
• 
The sponsor will comply with the requirements for publication of study results. 
In accordance with standard editorial and ethical practice, the sponsor will 
generally support publication of multicenter studies only in their entirety and not 
as individual site data. In this case, a coordinating investigator will be 
designated by mutual agreement. 
• 
Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements. 
Dissemination of Clinical Study Data 
For studies conducted in the EU under Regulations EU 536/2014: Consider whether 
submission of results of the clinical study will be delayed more than one year after the 
end of trial and provide substantiated reasons. Provide justification if a single summary of 
results report will not be submitted for all study treatments used in the clinical study. 
• 
Disclosure of CSRs, periodic safety reports, and clinical study summary reports 
after review by regulatory authorities. This includes access to CSRs from studies 
with negative outcomes and from terminated development programs. 
• 
The posting of company-sponsored study information and tabular study results 
on the US National Institutes of Health’s website www.ClinTrials.gov and other 
publicly-accessible sites.  
• 
Publication planning and other activities related to non-promotional, peer-
reviewed publications, to ensure the scientific integrity and credibility of 
publication activities performed by or on behalf of the company. The granting of 
access to analyzable datasets from clinical studies through a secure system, 
following an independent assessment of the scientific merit of a rigorously 
defined research question from a third party.  
• 
Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report. The investigator 
will be provided reasonable access to statistical tables, figures, and relevant 
reports and will have the opportunity to review the complete study results at a 
GSK site or other mutually-agreeable location. 
• 
GSK will also provide the investigator with the full summary of the study 
results. The investigator is encouraged to share the summary results with the 
study participants, as appropriate. 
• 
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK 
Policy. 


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• 
A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g., 
laboratory data). The investigator is responsible for verifying that data entries 
are accurate and correct by physically or electronically signing the CRF.  
• 
The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF.  
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents.  
• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data.  
• 
Study monitors will perform ongoing source data verification to confirm that 
data entered into the CRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants 
are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.  
• 
Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/ equivalent summary or as locally agreed unless 
local regulations or institutional policies require a longer retention period. No 
records may be destroyed during the retention period without the written 
approval of the sponsor. No records may be transferred to another location or 
party without written notification to the sponsor.  
Source Documents 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• 
Data entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. 
The investigator may need to request previous medical records or transfer 
records, depending on the study. Also, current medical records must be 
available. 
• 
Definition of what constitutes source data can be found in SRM. 


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Study and Site Closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study treatment development 
 


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11.4. 
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study treatment, whether or not considered 
related to the study treatment. 
• 
Note: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study treatment. 
 
Events Meeting the AE Definition  
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses must be reported regardless of sequelae. 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy 
will be reported as AE or SAE if they fulfill the definition of an AE or SAE.  
 
Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the participant’s condition. 


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• 
The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
Results in death 
Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AE. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE must be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 
Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
• 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 


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influenza, and accidental trauma (e.g., sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
Is a congenital anomaly/birth defect 
Other situations: 
• 
Medical or scientific judgment must be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events must 
usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
Is associated with liver injury and impaired liver function defined as: 
• 
ALT 3 x ULN and total bilirubin* 2 x ULN (>35% direct), or 
• 
ALT 3 x ULN and INR** >1.5. 
* Serum bilirubin fractionation should be performed if testing is available; if 
unavailable, measure urinary bilirubin via dipstick. If fractionation is unavailable and 
ALT 3 x ULN and total bilirubin 2 x ULN, then the event is still to be reported as an 
SAE. 
** INR testing not required per protocol and the threshold value does not apply to 
participants receiving anticoagulants. If INR measurement is obtained, the value is to 
be recorded on the SAE form. 
Refer to Appendix 7 for liver chemistry follow-up procedures. 
 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs: 
• 
Myocardial infarction/unstable angina 
• 
Congestive heart failure 
• 
Arrhythmias 
• 
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• 
Pulmonary hypertension 
• 
Cerebrovascular events/stroke and transient ischemic attack 
• 
Peripheral arterial thromboembolism 
• 
Deep venous thrombosis/pulmonary embolism 
• Revascularization 
 
Recording AE and SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
• 
The investigator will then record all relevant AE/SAE information in the CRF. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK /AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:  
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated.  
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL*.  
Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL**.  
Grade 4: Life-threatening consequences; urgent intervention indicated.  
Grade 5: Death related to AE. 
 


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*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc. 
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study treatment 
and each occurrence of each AE/SAE. 
• 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
• 
The investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study treatment 
administration will be considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK. 
• 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE and SAE 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK 
to elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 


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Reporting of SAE to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• 
The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
The investigator or medically-qualified sub-investigator must show evidence 
within the eCRF (e.g., check review box, signature, etc.) of review and verification 
of the relationship of each SAE to IP/study participation (causality) within 72 
hours of SAE entry into the eCRF. 
• 
After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection tool 
has been taken off-line, then the site can report this information on a paper SAE 
form (see next section). 
• 
Contacts for SAE reporting can be found in SRM. 
 
SAE Reporting to GSK via Paper CRF 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to the SAE coordinator. Details provided in the SRM. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time 
frames. 
• 
Contacts for SAE reporting can be found in the SRM. 
 
 


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11.5. 
Appendix 5: Contraceptive Guidance and Collection of 
Pregnancy Information 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 
Women in the following categories are not considered WOCBP 
1 
Premenarchal 
2 
Premenopausal females with ONE of the following: 
• 
Documented hysterectomy 
• 
Documented bilateral salpingectomy 
• 
Documented bilateral oophorectomy 
• 
For individuals with permanent infertility due to an alternate medical cause 
other than the above, (e.g., mullerian agenesis, androgen insensitivity), 
investigator discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s: review of participant’s 
medical records, medical examination, or medical history interview. 
3 
Postmenopausal females 
• 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high follicle stimulating hormone (FSH) level in 
the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or hormonal replacement therapy 
(HRT). However, in the absence of 12 months of amenorrhea, confirmation with 
more than one FSH measurement is required.  
• 
Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen hormonal highly effective contraception methods if 
they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment. 


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


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in this study and for 6 months following last dose of study treatment. This applies 
only to male participants who receive study intervention. 
• 
After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the partner’s 
pregnancy.  
• 
The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to GSK 
• 
Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of fetal 
status (presence or absence of anomalies) or indication for procedure.  
Female Participants who become pregnant 
• 
Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study and for 4 months following last 
dose of study treatment.  
• 
Information will be recorded on the appropriate form and submitted to GSK within 
24 hours of learning of a participant's pregnancy.  
• 
Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow up information on participant and neonate, which will 
be forwarded to GSK Generally, follow-up will not be required for longer than 6 to 8 
weeks beyond the estimated delivery date.  
• 
Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure.  
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be 
reported as an AE or SAE.  
• 
A spontaneous abortion is always considered to be an SAE and will be reported as 
such.  
• 
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study intervention by the investigator, will be reported to 
GSK as described in Appendix 4. While the investigator is not obligated to actively 
seek this information in former study participants, he or she may learn of an SAE 
through spontaneous reporting.  
Any female participant who becomes pregnant while participating will discontinue study 
intervention.  
 


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11.6. 
Appendix 6: Genetics 
USE/ANALYSIS OF DNA 
• 
Genetic variation may impact a participant’s response to therapy, susceptibility, 
severity and progression of disease. Variable response to therapy may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and 
excretion; mechanism of action of the drug; disease etiology; and/or molecular 
subtype of the disease being treated. Therefore, where local regulations and IRB/IEC 
allow, a 6-mL blood sample will be collected from participants who have consented 
to participate for DNA analysis. 
• 
DNA samples will be used for research related to belantamab mafodotin or Multiple 
Myeloma and related diseases. They may also be used to develop tests/assays 
including diagnostic tests related to belantamab mafodotin or study treatments of this 
drug class, and Multiple Myeloma. Genetic research may consist of the analysis of 
one or more candidate genes or the analysis of genetic markers throughout the 
genome or analysis of the entire genome (as appropriate). 
• 
DNA samples will be analyzed for described planned analyses. Additional analyses 
will be conducted if it is hypothesized that this may help further understand the 
clinical data.  
• 
The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to belantamab mafodotin or study treatments of this class. 
The results of genetic analyses may be reported in the clinical study report or in a 
separate study summary. 
• 
The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality.  
• 
The samples will be retained while research on belantamab mafodotin (or study 
treatments of this class) or Multiple Myeloma continues but no longer than 15 years 
after the last subject last visit or other period as per local requirements. 
 


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11.7. 
Appendix 7: Liver Safety: Required Actions and Follow-up 
Assessments and Study Treatment Rechallenge Guidelines 
Phase I/II liver chemistry stopping and increased monitoring criteria have been 
designed to assure participant safety and evaluate liver event etiology. 
Liver Chemistry Stopping Criteria – Liver Stopping Event 
ALT-absolute 
ALT 5xULN 
ALT Increase 
ALT 3xULN persists for 4 weeks 
Bilirubin1, 2 
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin)  
INR2  
ALT 3xULN and INR >1.5, if INR measured 
Cannot Monitor 
ALT 3xULN and cannot be monitored weekly for 4 weeks 
Symptomatic3 
ALT 3xULN associated with symptoms (new or worsening) believed to be 
related to liver injury or hypersensitivity 
Required Actions and Follow up Assessments following ANY Liver Stopping Event 
Actions 
Follow Up Assessments 
• 
Report the event to GSK within 24 hours 
• 
Complete the liver event CRF and complete 
an SAE data collection tool if the event also 
meets the criteria for an SAE2 
• 
Perform liver event follow up assessments  
• 
Monitor the participant until liver chemistries 
resolve, stabilize, or return to within 
baseline (see MONITORING below) 
• 
Do not restart/rechallenge participant with 
study treatment unless allowed per protocol 
and GSK Medical Governance approval is 
granted (refer to language within this 
Appendix)  
• 
If restart/rechallenge not allowed per 
protocol or not granted, permanently 
discontinue study treatment and may 
continue participant in the study for any 
protocol specified follow up assessments  
MONITORING: 
For bilirubin or INR criteria:  
• 
Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
• 
Viral hepatitis serology4 
• 
Only in those with underlying chronic hepatitis B 
at study entry (identified by positive hepatitis B 
surface antigen) quantitative hepatitis B DNA and 
hepatitis delta antibody5.  
• 
Blood sample for pharmacokinetic (PK) analysis, 
if it can be obtained within 45 days after last dose  
• 
Serum creatine phosphokinase (CPK) and 
lactate dehydrogenase (LDH). 
• 
Fractionate bilirubin, if total bilirubin2xULN 
• 
Obtain complete blood count with differential to 
assess eosinophilia 
• 
Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity, on 
the AE report form 
• 
Record use of concomitant medications on the 
concomitant medications report form including 
acetaminophen, herbal remedies, other over the 
counter medications 
• 
Record alcohol use on the liver event alcohol 
intake case report form 


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liver event follow up assessments within 24 
hrs 
• 
Monitor participants twice weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
• 
A specialist or hepatology consultation is 
recommended 
For All other criteria:  
• 
Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow up assessments within 24-
72 hrs  
• 
Monitor participants weekly until liver 
chemistries resolve, stabilize or return to 
within baseline 
For bilirubin or INR criteria: 
• 
Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney microsomal 
antibodies, and quantitative total immunoglobulin 
G (IgG or gamma globulins). 
• 
Serum acetaminophen adduct HPLC assay 
(quantifies potential acetaminophen contribution 
to liver injury in participants with definite or likely 
acetaminophen use in the preceding week 
[James, 2009]) Note: not required in China  
• 
Liver imaging (ultrasound, magnetic resonance, 
or computerized tomography) and /or liver biopsy 
to evaluate liver disease; complete Liver Imaging 
and/or Liver Biopsy CRF forms. 
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that participant if ALT 3xULN and bilirubin 2xULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable urinary 
bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury.  
2. All events of ALT 3xULN and bilirubin  2xULN (>35% direct bilirubin) or ALT 3xULN and INR>1.5, if INR 
measured which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE 
(excluding studies of hepatic impairment or cirrhosis); INR measurement is not required and the threshold 
value stated will not apply to participants receiving anticoagulants 
3. New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, 
rash or eosinophilia) 
4. Includes: Hepatitis A IgM antibody; Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM); Hepatitis 
C RNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing); Hepatitis E IgM antibody  
5. If hepatitis delta antibody assay cannot be performed, it can be replaced with a PCR of hepatitis D RNA virus 
(where needed) [Le Gal, 2005]. 
6. Record the date/time of the PK blood sample draw and the date/time of the last dose of study treatment prior to 
blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s best 
approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected 
in the time period indicated above, do not obtain a PK sample.  
 


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Phase I/II Oncology liver chemistry increased monitoring criteria with continued 
therapy 
Liver Chemistry Increased Monitoring Criteria – Liver Monitoring Event 
Criteria 
Actions 
ALT 3xULN but <5xULN and 
 bilirubin <2xULN, without symptoms believed 
to be related to liver injury or hypersensitivity 
and who can be monitored weekly for 4 weeks 
 
• 
Notify the GSK medical monitor within 24 hours 
of learning of the abnormality to discuss 
participant safety.  
• 
Participant can continue study treatment  
• 
Participant must return weekly for repeat liver 
chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) until they resolve, stabilize or return to 
within baseline  
• 
If at any time participant meets the liver chemistry 
stopping criteria, proceed as described above 
• 
If, after 4 weeks of monitoring, ALT <3xULN and 
bilirubin <2xULN, monitor participants twice 
monthly until liver chemistries normalize or return 
to within baseline. 
11.7.1. 
Liver Safety Drug Restart or Re-Challenge Guidelines 
If participant meets liver chemistry stopping criteria do not restart/re-challenge 
participant with study treatment unless all the following conditions are met: 
• 
GSK Medical Governance approval is granted (as described below) 
• 
IRB/IEC approval is obtained, if required 
• 
Separate consent for treatment restart/re-challenge is signed by the participant 
If GSK Medical Governance approval to restart/re-challenge participant with study 
treatment is not granted, then participant must permanently discontinue study treatment 
and may continue in the study for protocol-specified follow up assessments. 
11.7.1.1. 
Re-challenge Following Liver Stopping Events that are Possibly 
Related to Study Treatment 
Re-challenge refers to resuming study treatment following drug-induced liver injury 
(DILI). Because of the risks associated with re-challenge after DILI, this should only be 
considered for a participant for whom there is compelling evidence of benefit from a 
critical or life-saving medicine, there is no alternative approved medicine available, and a 
benefit: risk assessment of re-challenge is considered to be favorable. 
Following DILI, drug re-challenge is associated with a 13% mortality across all drugs in 
prospective studies [Andrade, 2009]. Clinical outcomes vary by drug with nearly 50% 


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fatality with halothane re-administered within 1 month of initial injury. However, some 
drugs seldom result in recurrent liver injury or fatality.  
Risk factors for a fatal drug re-challenge outcome include the following: 
• 
Hypersensitivity1 with initial liver injury (e.g., fever, rash, eosinophilia)  
• 
Jaundice or bilirubin >2 x ULN with initial liver injury (direct bilirubin >35% of 
total) 
• 
Participant currently exhibits severe liver injury defined by ALT >3 x ULN, bilirubin 
>2 x ULN (direct bilirubin >35% of total), or INR >1.5 
• 
SAE or fatality has been observed with drug rechallenge [Papay, 2009; Hunt, 2010] 
• 
Evidence of drug-related preclinical liability (e.g., reactive metabolites; 
mitochondrial impairment) [Hunt, 2010] 
Approval by GSK for re-challenge with study treatment can be considered under the 
following conditions: 
• 
Investigator requests consideration of re-challenge with study treatment for a 
participant who is receiving compelling benefit with study treatment that exceeds 
risk, and no effective alternative therapy is available.  
• 
IRB/IEC approval for re-challenge with study treatment must be obtained, as 
required.  
• 
If the re-challenge is approved by GSK Medical Governance in writing, the 
participant must be provided with a clear description of the possible benefits and 
risks of study treatment administration including the possibility of recurrent, more 
severe liver injury or death.  
• 
The participant must also provide signed informed consent specifically for the 
re-challenge with study treatment. Documentation of informed consent must be 
recorded in the study chart.  
• 
Study treatment must be administered at the dose specified by GSK. 
• 
Participants approved by GSK Medical Governance for re-challenge with study 
treatment must return to the clinic twice a week for liver chemistry tests until stable 
liver chemistries have been demonstrated and then standard laboratory monitoring 
may resume as per protocol. 
• 
If after study treatment re-challenge, participant meets protocol-defined liver 
chemistry stopping criteria, study treatment must be permanently discontinued.  
• 
GSK medical monitor, and the IRB/IEC as required, must be informed of the 
participant’s outcome following study treatment re-challenge.  
• 
GSK must be notified of any AEs as per Section 8.2.4. 


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11.7.1.2. 
Re-challenge Following Transient Liver Stopping Events Not Related to 
Study Treatment 
Restart refers to resuming study treatment following liver stopping events in which there 
is a clear underlying cause (other than DILI) of the liver event (e.g., biliary obstruction, 
pancreatic events, hypotension, and acute viral hepatitis). Furthermore, there should be 
no evidence of alcoholic hepatitis or hypersensitivity, and the study treatment should not 
be associated with human leukocyte antigen (HLA) markers of liver injury. 
Approval by GSK for study treatment restart can be considered under the following 
conditions: 
• 
Investigator requests consideration for study treatment restart if liver chemistries 
have a clear underlying cause (e.g., biliary obstruction, hypotension and liver 
chemistries have improved to normal or are within 1.5 x baseline and ALT 
<3 x ULN). 
• 
Possible study treatment-related liver injury has been excluded by the investigator 
and the study team. This includes the absence of markers of hypersensitivity 
(otherwise unexplained fever, rash, eosinophilia). Where a study treatment has an 
identified genetic marker associated with liver injury (e.g., lapatinib, abacavir, 
amoxicillin/clavulanate), the presence of the marker should be excluded. If study 
treatment-related liver injury cannot be excluded, the guidance on re-challenge in 
Section 11.7.1.1 will apply. 
• 
There is no evidence of alcoholic hepatitis. 
• 
IRB/IEC approval of study treatment restart must be obtained, as required. 
• 
If restart of study treatment is approved by GSK Medical Governance in writing, the 
participant must be provided with a clear description of the possible benefits and 
risks of study treatment administration including the possibility of recurrent, more 
severe liver injury or death. 
• 
The participant must also provide signed informed consent specifically for the study 
treatment restart. Documentation of informed consent must be recorded in the study 
chart. 
• 
Study treatment must be administered at the dose specified by GSK. 
• 
Participants approved by GSK Medical Governance for restarting study treatment 
must return to the clinic once a week for liver chemistry tests until stable liver 
chemistries have been demonstrated and then laboratory monitoring may resume as 
per protocol. 
• 
If after study treatment restart, participant meets protocol-defined liver chemistry 
stopping criteria, follow usual stopping criteria instructions. 
• 
GSK medical monitor, and the IRB/IEC as required, must be informed of the 
participant’s outcome following study treatment restart. 
• 
GSK must be notified of any AEs, as per Section 8.2.4. 


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11.7.2. 
References 
Andrade RJ, Robles M, Lucena MI. Rechallenge in drug-induced liver injury: the 
attractive hazard. Expert Opin Drug Saf. 2009;8:709-714. 
Hunt, CM. Mitochondrial and immunoallergic injury increase risk of positive drug 
rechallenge after drug-induced liver injury: A systematic review. Hepatol. 2010;52:2216-
2222. 
James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee 
WM. Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen 
Overdose and Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784. 
Le Gal F, Gordien E, Affolabi D, Hanslik T, Alloui C, Dény P, Gault E. Quantification of 
Hepatitis Delta Virus RNA in Serum by Consensus Real-Time PCR Indicates Different 
Patterns of Virological Response to Interferon Therapy in Chronically Infected Patients. J 
Clin Microbiol. 2005;43(5):2363–2369. 
Papay JI, Clines D, Rafi R, Yuen N, Britt SD, Walsh JS, Hunt CM. Drug-induced liver 
injury following positive drug rechallenge. Regul Tox Pharm. 2009;54:84-90.  
 
 


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11.8. 
Appendix 8: ECOG Performance Status 
Grade Descriptions 
0 
Normal activity. Fully active, able to carry on all pre-disease performance without restriction. 
1 
Symptoms, but ambulatory. Restricted in physically strenuous activity, but ambulatory and 
able to carry out work of a light or sedentary nature (e.g., light housework, office work). 
2 
In bed <50% of the time. Ambulatory and capable of all self-care, but unable to carry out 
any work activities. Up and about more than 50% of waking hours. 
3 
In bed >50% of the time. Capable of only limited self-care, confined to bed or chair more 
than 50% of waking hours. 
4 
100% bedridden. Completely disabled. Cannot carry on any self-care. Totally confined to 
bed or chair. 
5 
Dead. 
Oken,1982 


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


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Table 21 
Prophylactic Measures for Corneal Events Associated with 
Belantamab Mafodotin a 
Prophylactic 
Measurea 
Dose and Administration 
Timing 
Preservative-free 
artificial tears 
Administer in each eye at least 
4 to 8 times daily 
Administer daily beginning on Cycle 1 
Day 1 until EOT.  
Cooling eye mask 
May apply cooling eye mask to 
both eyes for approximately 
1 hour or as much as tolerated  
During belantamab mafodotin infusion 
administration in the first hour for up to 
4 hours, as tolerated 
a. 
Dose modifications and treatment for ocular toxicities are discussed in Section 6.2 
 
Table 22 
GSK/KVA Scale for Corneal Events Associated with Belantamab 
Mafodotin a 
Measure 
Grade 1 per 
GSK/KVA 
Scale  
Grade 2 per 
GSK/KVA Scale 
Grade 3 per 
GSK/KVA Scale 
Grade 4 per 
GSK/KVA 
Scale 
Ophthalmic 
exam 
findings 
Mild superficial 
keratopathy 
(change from 
baseline) 
 
Moderate punctate 
keratopathy 
and/or 
Mild/patchy 
microcysts 
and/or 
Mild/patchy Epithelial 
or stromal edema 
and/or 
Sub-epithelial haze 
(peripheral)  
and/or 
Active stromal opacity 
(peripheral) 
Severe punctate 
keratopathy 
and/or 
Diffuse microcysts 
and/or 
Diffuse Epithelial or 
stromal edema 
and/or 
Sub-epithelial haze 
(central)  
and/or 
Active stromal opacity 
(central) 
Corneal ulcer 
Visual 
Acuity b, c 
Change of 1 line 
from baseline 
Change of 2-3 lines 
from baseline and not 
worse than 20/200b 
Change of more than 3 
lines from baseline and 
not worse than 20/200b 
Worse than 
Vision 20/200b 
Note: Standardized guidance for grading ophthalmic findings associated with belantamab mafodotin is provided to sites 
in the ophthalmology SRM. Ophthalmic exam findings as described must be present in a participant to utilize 
GSK’s scale.  
a. 
Grading is based on most severe finding. If eyes differ in severity, GSK grading should be based on the more 
severe eye. 
b. 
Change in visual acuity should be due to corneal events. If change in vision is for reason other than corneal 
events, ophthalmic exam findings will drive event grading.  
c. 
See Table 23 for additional guidance on how to grade changes in visual acuity depending on baseline vision. If a 
participant has a baseline visual acuity of 20/200 or worse in an eye, ophthalmic exam findings will drive event 
grading. 
 
 
 


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


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11.10. 
Appendix 10: Modified Diet in Renal Disease (MDRD) 
Formula 
The MDRD formula for calculating the estimated glomerular filtration rate (eGFR) is as 
follows: 
eGFR (mL/min/1.73 m2) = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (1.212 if 
African American)  
 
GFR is expressed in mL/min/1.73 m2, Scr is serum creatinine expressed in mg/dL, and 
age is expressed in years.  
The link below will auto-calculate the creatinine clearance: http://nephron.org/cgi-
bin/MDRD_GFR/cgi 


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Appendix 11: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
Amendment 5: 08-Oct-2020 
Overall Rationale for the Amendment:  
The protocol has been amended to provide updates based on analyses of data from the 
DREAMM-1, DREAMM-2 and the exposure QTc. The updates include the removal of 
ECG collection, unless clinically indicated, and updated contraception timeframe. The 
dose modification guidelines for belantamab mafodotin related corneal events was 
updated to align with the approved label and an appendix on Home Healthcare and 
Telemedicine Approaches was introduced as a result of the COVID-19 pandemic to 
ensure sites and participants had alternate approaches to assist participants to continue 
receiving care while maintaining protocol adherence. 
Section # and Name Description of Change 
Brief Rationale  
Section 2 Schedule 
of Activities  
Study Assessment ECG and 
associated footnotes with mention of 
ECGs (footnote 10, 12, 13) amended to 
remove ECG unless clinically indicated. 
 
 
Table 2, footnote 27 – deletion of text 
related to discontinuation  
 
 
Table 3, footnote 6 – clarified  
 
 
Table 3, footnote 8, updated pregnancy 
timeframe  
Table 3, ECG assessment and footnote 
9 removed  
 
Triplicate ECGs were removed 
because the exposure-QTc 
analysis demonstrated that the 
likelihood of a QTc prolongation 
>10 msec is very low following 
administration of belantamab 
mafodotin. 
 
Duplication of text found in 
Table 3, schedule of activities 
for end of treatment and follow 
up 
 
Clarified for consistency with 
Section 7.2.3 Corneal 
Supportive Care Guidelines 
 
To align with current investigator 
brochure 
ECGs are to be performed as 
clinically indicated  


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


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Section # and Name Description of Change 
Brief Rationale  
Section 7.2 Dose 
Modifications 
Table 13 Dose modification guidelines 
for belantamab mafodotin treatment 
related corneal events amended to 
remove symptoms 
Updated to match the current 
approved label 
Section 8.2.3 QTc 
Interval Stopping 
Criteria 
Section removed 
Based on the exposure-QTc 
analysis results, the likelihood of 
a meaningful QTc 
prolongation (>10 msec) is very 
low following administration of 
belantamab mafodotin. 
Section 9 Study 
Assessments and 
procedures 
Removal of ECGs as a study 
assessment  
Based on the exposure-QTc 
analysis results, the likelihood of 
a meaningful QTc 
prolongation (>10 msec) is very 
low following administration of 
belantamab mafodotin. 
Section 9.3 
Treatment of 
Overdose 
Updated timeframe for resolution of 
AEs/SAEs and concentrations of 
belantamab mafodotin.  
Removed restriction of 
timeframe of 3 months as the 
timeframe can vary. 
 
Section 9.4.4 
Electrocardiogram 
Section removed 
Triplicate ECGs were removed 
because the exposure-QTc 
analysis demonstrated that the 
likelihood of a QTc prolongation 
>10 msec is very low following 
administration of belantamab 
mafodotin. 
 
Section 9.4.6 Patient 
Reported Outcome 
Version of the 
Common Term 
Criteria for Adverse 
Events (PRO-
CTCAE) 
Updated to allow options for 
participants to complete by phone or 
verbal interview 
 
Updated to provide options for 
PRO CTCAE completion  
 
Section 10.5.8 Other 
Analyses 
Addition of COVID-19 analysis 
Due to the pandemic an analysis 
will be completed and outlined in 
the reporting and analysis plan. 
12.5 Appendix 5: 
Contraception 
Updated timeframe for contraception 
usage in males and females.  
To align with current investigator 
brochure 


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Section # and Name Description of Change 
Brief Rationale  
Guidance and 
Collection of 
Pregnancy 
Information and 
Section 9.2.8 
Pregnancy 
Section 12.13 
Appendix 13 Home 
Healthcare and 
Telemedicine 
Approaches 
Addition of Appendix  
As a result of COVID-19 
pandemic, alternate approaches 
were introduced to allow 
participants to adhere to the 
protocol. 
Editorial/Document Formatting Changes  
Whole Document 
GSK2857916 or GSK’916 replaced with 
belantamab mafodotin 
Use generic name  
Whole Document  
GSK Scale replace with GSK/KVA 
Scale 
To align with belantamab 
mafodotin label which notes the 
KVA scale  
 
Amendment 4: 21-Oct-2019 
Overall Rationale for the Amendment:  
The protocol has been amended to provide updates based on data from the primary 
analysis and address feedback from regulatory agencies.  
 
Section # and Name Description of Change 
Brief Rationale  
Section 2 Schedule 
of Activities  
Table 2, Footnote 7 added reference to 
increase monitoring for hematologic 
events 
 
 
Table 2, Footnote 10 clarification of 
timeframe to perform triplicate 
electrocardiograms (ECGs) 
 
Based on percentage of Grade 
(Gr) 3-4 hematologic events it 
was determined that more 
frequent monitoring should be 
recommended  
 
To align with Section 9.4.4 
 
Clarification of bone marrow 
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Section # and Name Description of Change 
Brief Rationale  
Table 2, Footnote 21: clarification  
 
 
Table 2, treatment for steroid eye drops 
deleted, footnote 26a updated 
 
 
Table 3, Footnote 6 correction of 
timeframe for follow up of corneal 
toxicity 
 
Table 3, Footnote 8 increased 
timeframe for contraception usage in 
males and females.  
 
 
 
 
 
 
Table 3, Footnote 10 Updated 
language on requirements for disease 
assessments required to be completed 
when confirming disease progression. 
 
 
Table 3, Footnote 15; Clarification  
 
Residual disease (MRD) testing 
timeframe. 
 
 
Removed prophylactic use of 
steroid eye drops based on 
based on data from the primary 
analysis 
 
Aligned with Section 7.2.3 
 
 
In May 2019, FDA released 
updated reproductive toxicity 
recommendations for oncology 
pharmaceuticals, including 
guidance on labelling the 
duration of contraception 
following cessation of therapy, to 
minimize any potential risk to a 
developing embryo or fetus 
Inclusion criteria 8&9 not 
updated to align as enrollment 
has closed 
 
 
Clarification of confirmatory 
disease progression 
assessments 
 
 


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


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


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


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Section # and Name Description of Change 
Brief Rationale  
12.9 Appendix 9: 
GSK Corneal Event 
Severity Scale and 
Mitigation Strategy 
for GSK2857916 
Treatment Related 
Corneal Events  
 
Table 21: Updated to remove use of 
prophylactic steroid eye drops 
 
 
 
 
 
Table 23: Added 20/15 as a baseline 
vision 
 
Removed prophylactic use of 
steroid eye drops based on data 
from the primary analysis 
 
 
 
The visual acuity scale did not 
reference vision better than 
20/20. 
 
 


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


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


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


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


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


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


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


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


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


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


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Section # and Name 
Description of Change 
Brief Rationale 
Cover Page 
 
Study title updated 
A Phase II, Open Label, 
Randomized, Two-Arm Study to 
Investigate the Efficacy and Safety 
of Two Doses of the Antibody Drug 
Conjugate GSK2857916 in 
Participants with Multiple Myeloma 
Who Had 3 or More Prior Lines of 
Treatment, Are Refractory to a 
Proteasome Inhibitor and an 
Immunomodulatory Agent and Have 
Failed an Anti-CD38 Antibody 
(DREAMM 2). 
Title updated to reflect the 
design change (see below) 
Synopsis  
Changed text of Synopsis to reflect 
changes to the text of the protocol 
See below for all significant 
changes 
All sections 
Replaced the word ‘patient’ with 
‘participant’ and ‘subset’ replaced 
with ‘sub-study’. 
New references added 
 
Section 2 Schedule of 
Activities 
 
 
 
Separate schedule tables for 
Screening assessments, on study 
assessment, ‘end of treatment 
assessment and follow-up 
assessment have been included. 
Deletion of coagulation criteria 
(INR) for determining adequate 
organ system function 
Removal of aspirate for flow 
cytometry  
Added PET/CT to confirm CR, sCR 
 
German exceptions to PET/CT 
The tables have been separated 
to clarify activities.  
 
 
Current liver event management 
guidelines do not require INR.  
Flow cytometry is not used in 
IMWG Kumar, 2016. 
Based on Kumar, 2016.  
Germany: approval by the 
German Federal Office for 
Radiation Protection is required 
prior to PET/CT or other x-rays 
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Section 3.1 Study 
Rationale  
 
Section 3.4.2 Corneal 
Events 
Section 3.4.3 
Pharmacokinetics 
Section 3.5.3 Overall 
Benefit- Risk 
Conclusions 
Ongoing FTIH study number has 
been changed from BMA117158 to 
BMA117159 
Additional information regarding 
corneal toxicity included 
Included new section 
‘Pharmacokinetics; with section 
number 3.4.3 
Overall Benefit-Risk conclusions is 
updated to reflect the additional 
dose. 
Editorial changes 
 
 
 
To support the additional arm 
that includes dose level 
2.5mg/kg 
Updated to reflect the change in 
study design. 
Section 4 Objectives 
and Endpoints, 
Primary Objective 
 
 
Exploratory Objective 
 
 
 
 
Ocular Sub-Study 
Objective 
 
Primary objective has been 
modified: to evaluate the clinical 
efficacy of 2 doses of GSK2857916 
in participants with 
relapsed/refractory multiple 
myeloma by overall response rate 
 
New exploratory endpoint has been 
included: To assess the safety, 
efficacy, immunogenicity, and 
pharmacokinetics of GSK2857916 
in a lyophilized configuration (n=25) 
 
Number of participants to evaluate 
the effect of topical corticosteroids 
on corneal findings has been 
increased to 30 (15 in each dose 
arm). 
Updated to reflect the change in 
study design.  
 
 
To gain clinical experience with 
the lyophilized configuration.  
 
 
 
Number increased to reflect the 
additional arm and increased 
study sample size.  
Section 5 Study 
Design 
 
Study design description and the 
Study Schema revised. 
 
Efficacy and safety results from the 
interim analysis will not be shared 
with investigators or other study/site 
personnel 
Language and the schema 
modified to clarify changes in 
study design have been added, 
including the addition of a 
second arm, change to the total 
number of participants, IA to 
assess futility, IDMC to review 
IA results, and an additional 
cohort of participants (n=25) 
who will receive the lyophilized 
configuration.  


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


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


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


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


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


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


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


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


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11.13. 
Appendix 13: Home Healthcare and Telemedicine 
Approaches 
Home Healthcare (General Visit): 
Where applicable country and local regulations and infrastructure allow, home healthcare 
may be permitted. Home healthcare is defined as a remote visit(s) that is/are performed at 
the participant’s home by qualified personnel (e.g. nurse).  
Activities that may be done as part of a home healthcare visit must follow the schedule 
provided in the SoA (Section 1.2) and include:  
• Collection of blood and urine samples including:  
o Safety assessments which may include routine blood and urine 
sampling 
o Efficacy assessments to be sent to central lab 
• Measurement of vital signs (BP, heart rate, body temperature). 
• Identification and reporting of concomitant medications. 
• Patient reported signs and symptoms, or abnormalities noted based on vital 
signs are reported to the Principal Investigator to determine if they meet the 
definition of an AEs/SAEs. 
Note: The investigator or other qualified medical professional must ensure 
reporting of AEs and SAEs is completed in accordance with the protocol and 
applicable regulations and that the appropriate medical intervention, therapeutic 
intervention, and/or support measures are instituted, as necessary.  
The participant should be informed of any potential risks associated with Home 
Healthcare and sign a revised Informed Consent Form if required. IRB/Ethics committee 
should be informed and/or approve of this change in approach and the process 
documented in study files. 
 


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Home Healthcare (Ophthalmologic Exam) 
Where applicable country and local regulations and infrastructure allow, protocol-
required eye exams may be done in the participant’s home or specified alternative eye 
care specialist clinic.  
All protocol specific assessments should be completed by the alternative eye care 
specialist at the clinic. Activities that may be done as part of in-home eye exams, must 
follow the schedule provided in the SoA (Section 1.2) and include:  
• Best Corrected Visual Acuity, or Visual Acuity (VA) by near-chart visual 
acuity/pinhole. 
• Slit lamp exam  
• Intraocular pressure measurement & time checked  
• Dilated funduscopic exam  
The participant should be informed of any potential risks associated with Home 
Healthcare Ophthalmologic exams and sign a revised Informed Consent Form if required. 
IRB/Ethics committee should be informed and/or approve of this change in approach and 
the process documented in study files. 
Telemedicine 
Where applicable country and local regulations and infrastructure allow, telemedicine 
visits may be permitted. Telemedicine visits are defined as online (virtual) visits which 
will use secure video conference, phone calls, a web portal and/or mobile application as a 
way of communicating with and monitoring the participant’s progress. Telemedicine 
visits are conducted by an investigator or other qualified medical professional and may be 
done in combination with visits from Home Healthcare personnel (see above). 
Activities that may be done as part of a telemedicine visit include: 
• Medical evaluation of the participant  
• Identification and reporting of concomitant medications. 
• Identification, management, and reporting of AEs and SAEs.  
Note: The investigator or other qualified medical professional must ensure 
reporting of AEs and SAEs is completed in accordance with the protocol and 
applicable regulations and that the appropriate medical intervention, therapeutic 
intervention, and/or support measures are instituted, as necessary. Participants 
utilizing telemedicine can report AEs at any time via an app, phone call or 
videoconference with site staff. 
The participant should be informed of any potential risks associated with the virtual 
medium and sign a revised Informed Consent Form if required. IRB/Ethics committee 
should be informed and/or approve of this change in approach and the process 
documented in study files. 


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Remote Patient Reported Outcomes (PRO) Administration 
 Where applicable country and local regulations and infrastructure allow, remote PRO 
administration may be permitted. Remote PRO administration is defined administration 
of protocol PROs by a qualified third party over the telephone. The remote PRO 
Administrator will use the versions of the PROs designed for verbal administration. The 
remote PRO Administrator will create a data change form with the participants’ 
responses and send to the third party vendor for the study to add to the study portal.  
The participant should be informed of any potential risks associated with the remote PRO 
administration and sign a revised Informed Consent Form if required. IRB/Ethics 
committee should be informed and/or approve of this change in approach and the process 
documented in study files. 
 
 
 
 


Signature Page for  205678 TMF-13990464 v2.0
Signature Page for TMF-13990464 v2.0
Reason for signing: Approved
Name: 
Role: A
Date of signature: 19-Nov-2021 13:48:31 GMT+0000
PPD

SAP_003.pdf: 
Statistical Analysis Plan
Study ID:  205678
Official Title of Study: Reporting and Analysis Plan for A Phase II, Open Label,
Randomized, Two-Arm Study to Investigate the Efficacy and Safety of Two Doses of the 
Antibody Drug Conjugate GSK2857916 in Participants with Multiple Myeloma Who
Had 3 or More Prior Lines of Treatment, Are Refractory to Proteasome Inhibitor and an 
Immunomodulatory Agent and Have Failed an Anti-CD38 Antibody (DREAMM 2)
NCTID: NCT03525678
Date of Document: 06 Apr 2022


 
CONFIDENTIAL 
 
The GlaxoSmithKline group of companies 
 
205678 
1 
Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
Title 
: Reporting and Analysis Plan for A Phase II, Open Label, 
Randomized, Two-Arm Study to Investigate the Efficacy and 
Safety of Two Doses of the Antibody Drug Conjugate 
GSK2857916 in Participants with Multiple Myeloma Who 
Had 3 or More Prior Lines of Treatment, Are Refractory to a 
Proteasome Inhibitor and an Immunomodulatory Agent and 
Have Failed an Anti-CD38 Antibody (DREAMM 2) 
Compound Number  : GSK2857916 
Effective Date  
:  06 Apr 2022 
 
Description: 
• 
The purpose of this RAP is to describe the planned analyses and outputs to be 
included in the Clinical Study Report for Protocol 205678/ Amendment 06 (TMF-
13990464 ). 
• 
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) deliverable. 
 
RAP Author(s): 
Approver 
Approval 
Method 
 
Senior Statistician (Oncology, Clinical Statistics) 
TMF 
 
 (Clinical Pharmacology Modelling & Simulation) 
E-mail 
 
Copyright 2022 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited.
PPD
PPD
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2 
RAP Team Approvals: 
Approver 
Approval Method 
  
TMF/E-mail 
 (Oncology, ES Clinical) 
 
 Clinical Scientist 
TMF/E-mail 
 
Safety Development Leader (Pharmacovigilance, Safety & 
Medical Governance) 
 
E-mail 
 
Programming Leader (Oncology, Clinical Programming) 
TMF/E-mail 
Clinical Statistics and Clinical Programming Line Approvals: 
Approver 
Approval Method 
 
 (Oncology, Clinical Statistics) 
TMF/E-mail 
 
 (Oncology, Clinical Programming) 
 
TMF/E-mail 
 
PPD
PPD
PPD
PPD
PPD
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3 
TABLE OF CONTENTS 
PAGE 
TABLE OF CONTENTS .................................................................................................. 3 
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)............................................................. 11 
2.3. 
Study Design .............................................................................................. 14 
2.4. 
Statistical Hypotheses / Statistical Analyses ............................................... 15 
3. 
PLANNED ANALYSES .......................................................................................... 16 
3.1. 
Interim Analyses ......................................................................................... 16 
3.1.1. 
Futility Stopping Rule Based on Group Sequential Design ........... 16 
3.1.1.1. 
Operating Characteristics of the Stopping 
Rules for Futility .......................................................... 17 
3.1.2. 
Additional Comparative Futility Stopping Rule Based on 
Bayesian Approach ...................................................................... 18 
3.2. 
Primary Analyses ........................................................................................ 19 
4. 
ANALYSIS POPULATIONS ................................................................................... 19 
4.1. 
Protocol Deviations ..................................................................................... 21 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 22 
5.1. 
Study Treatment & Sub-group Display Descriptors ..................................... 22 
5.2. 
Baseline Definitions .................................................................................... 22 
5.3. 
Examination of Covariates, Other Strata and Subgroups ............................ 23 
5.3.1. 
Covariates and Other Strata ........................................................ 23 
5.3.2. 
Examination of Subgroups ........................................................... 23 
5.4. 
Other Considerations for Data Analyses and Data Handling 
Conventions ................................................................................................ 24 
6. 
STUDY POPULATION ANALYSES ....................................................................... 25 
6.1. 
Overview of Planned Study Population Analyses ........................................ 25 
6.2. 
Disposition of Subjects ................................................................................ 25 
6.3. 
Demographic and Baseline Characteristics ................................................. 25 
6.4. 
Treatment Compliance ................................................................................ 26 
6.5. 
Extent of Exposure ..................................................................................... 26 
6.6. 
Concomitant Medications ............................................................................ 27 
6.7. 
Subsequent Anti-Cancer Therapies ............................................................ 28 
7. 
EFFICACY ANALYSES .......................................................................................... 29 
7.1. 
Primary Efficacy Analyses .......................................................................... 29 
7.1.1. 
Overall Response Rate (ORR) based on IRC assessment .......... 29 
7.1.1.1. 
Derivation of Confirmed Response ............................. 29 
7.1.2. 
Summary Measure ...................................................................... 31 
7.1.3. 
Population of Interest ................................................................... 32 


 
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7.1.4. 
Statistical Analyses / Methods ..................................................... 32 
7.2. 
Secondary Efficacy Analyses ...................................................................... 33 
7.2.1. 
Endpoint / Variables ..................................................................... 33 
7.2.1.1. 
ORR based on Investigator Assessment .................... 33 
7.2.1.2. 
Clinical Benefit Rate (CBR) ........................................ 33 
7.2.1.3. 
Duration of Response (DoR) ...................................... 33 
7.2.1.4. 
Time to Response (TTR) ............................................ 33 
7.2.1.5. 
Progression Free Survival (PFS) ................................ 34 
7.2.1.6. 
Time to Progression (TTP) ......................................... 35 
7.2.1.7. 
Overall Survival (OS) .................................................. 37 
7.2.2. 
Summary Measure ...................................................................... 37 
7.2.3. 
Population of Interest ................................................................... 38 
7.2.4. 
Statistical Analyses / Methods ..................................................... 38 
7.3. 
Exploratory Efficacy Analyses ..................................................................... 39 
7.3.1. 
Endpoint / Variables ..................................................................... 39 
7.3.1.1. 
Minimal Residual Disease (MRD) Negativity 
Rate ........................................................................... 39 
7.3.2. 
Summary Measure ...................................................................... 39 
7.3.2.1. 
MRD Negativity Rate .................................................. 39 
7.3.3. 
Population of Interest ................................................................... 39 
7.3.4. 
Statistical Analyses / Methods ..................................................... 39 
8. 
SAFETY ANALYSES ............................................................................................. 40 
8.1. 
Adverse Events Analyses ........................................................................... 40 
8.2. 
Adverse Events of Special Interest Analyses .............................................. 41 
8.2.1. 
Thrombocytopenia, infusion related reactions, and 
neutropenia .................................................................................. 41 
8.2.2. 
Eye disorder (CTCAE) ................................................................. 42 
8.2.3. 
Corneal events (GSK scale)......................................................... 42 
8.3. 
Deaths and Serious Adverse Events ........................................................... 46 
8.4. 
Adverse Events Leading to Discontinuation and Dose Modification ............ 46 
8.5. 
Ocular findings from ophthalmic exam ........................................................ 46 
8.6. 
Pregnancies ................................................................................................ 50 
8.7. 
Clinical Laboratory Analyses ....................................................................... 50 
8.7.1. 
Analyses of Liver Function Tests ................................................. 51 
8.8. 
Other Safety Analyses ................................................................................ 51 
8.8.1. 
Performance Status ..................................................................... 51 
8.8.2. 
ECG ............................................................................................. 51 
8.8.3. 
LVEF ........................................................................................... 52 
8.8.4. 
Anti-Drug Antibody analyses ........................................................ 52 
9. 
PHARMACOKINETIC ANALYSES ......................................................................... 53 
9.1. 
Drug Concentration Measures .................................................................... 53 
9.1.1. 
Non-compartmental Analysis ....................................................... 53 
9.2. 
Population of Interest .................................................................................. 54 
9.3. 
Statistical Analyses / Methods .................................................................... 54 
9.3.1. 
Statistical Methodology Specification ........................................... 54 
9.3.1.1. 
Assessment of Accumulation Ratio ............................ 54 
10. POPULATION PHARMACOKINETIC (POPPK) ANALYSES .................................. 55 
11. PHARMACODYNAMIC AND BIOMARKER ANALYSES ........................................ 56 


 
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12. PHARMACOKINETIC / PHARMACODYNAMIC ANALYSES ................................. 57 
12.1. 
Exposure-Response for Efficacy and Safety Endpoints .............................. 57 
12.2. 
Concentration-QTc Analyses ...................................................................... 57 
13. HEALTH OUTCOMES ANALYSIS ......................................................................... 58 
13.1. 
European Organization for Research and Treatment of Cancer 
Quality of Life Questionnaire 30-item Core module (EORTC QLQ-
C30) ............................................................................................................ 58 
13.2. 
European Organization for Research and Treatment of Cancer 
Quality of Life Questionnaire 20-item Multiple Myeloma module 
(EORTC QLQ-MY20) .................................................................................. 58 
13.3. 
Patient-Reported Outcome Version of the Common Term Criteria 
for Adverse Events (PRO-CTCAE) ............................................................. 59 
13.4. 
National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-
25) .............................................................................................................. 59 
13.5. 
Ocular Surface Disease Index .................................................................... 60 
14. REFERENCES ....................................................................................................... 61 
15. APPENDICES ........................................................................................................ 63 
15.1. 
Appendix 1: Protocol Deviation Management and Definitions for Per 
Protocol Population ..................................................................................... 63 
15.1.1. 
Exclusions from Per Protocol Population ..................................... 63 
15.2. 
Appendix 2: Schedule of Activities .............................................................. 64 
15.2.1. 
Protocol Defined Schedule of Events ........................................... 64 
15.3. 
Appendix 3: Assessment Windows ............................................................. 65 
15.3.1. 
Definitions of Assessment Windows for Analyses ........................ 65 
15.4. 
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................ 66 
15.4.1. 
Study Phases .............................................................................. 66 
15.4.2. 
Treatment Emergent Flag for Adverse Events ............................. 68 
15.5. 
Appendix 5: Data Display Standards & Handling Conventions .................... 69 
15.5.1. 
Reporting Process ....................................................................... 69 
15.5.2. 
Reporting Standards .................................................................... 69 
15.5.3. 
Reporting Standards for Pharmacokinetic .................................... 70 
15.5.4. 
Extended Loss to Follow-up or Extended Time without an 
Adequate Assessment ................................................................. 70 
15.6. 
Appendix 6: Derived and Transformed Data ............................................... 71 
15.6.1. 
General ........................................................................................ 71 
15.6.2. 
Study Population .......................................................................... 71 
15.6.3. 
Efficacy ........................................................................................ 71 
15.6.4. 
Safety .......................................................................................... 72 
15.7. 
Appendix 7: Reporting Standards for Missing Data ..................................... 73 
15.7.1. 
Premature Withdrawals ................................................................ 73 
15.7.2. 
Handling of Missing Data ............................................................. 73 
15.7.2.1. Handling of Missing and Partial Dates ........................ 73 
15.8. 
Appendix 8: Values of Potential Clinical Importance ................................... 76 
15.8.1. 
Laboratory Values ........................................................................ 76 
15.8.2. 
ECG Parameters and vital signs .................................................. 76 
15.9. 
Appendix 9: Population Pharmacokinetic (PopPK) Analyses ...................... 77 
15.9.1. 
Population Pharmacokinetic (PopPK) Dataset 
Specification ................................................................................ 77 


 
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15.9.2. 
Population Pharmacokinetic (PopPK) Methodology ..................... 77 
15.10. Appendix 10: Pharmacokinetic / Pharmacodynamic Analyses .................... 78 
15.10.1. Pharmacokinetic / Pharmacodynamic Dataset 
Specification ................................................................................ 78 
15.10.2. Pharmacokinetic / Pharmacodynamic Methodology ..................... 78 
15.11. Appendix 11: Health outcome Analyses ...................................................... 79 
15.11.1. EORTC QLQ-C30 ........................................................................ 79 
15.11.2. EORTC QLQ-MY20 ..................................................................... 81 
15.11.3. NEI-VFQ-25 ................................................................................. 82 
15.12. Appendix 12: Abbreviations & Trade Marks ................................................ 85 
15.12.1. Abbreviations ............................................................................... 85 
15.12.2. Trademarks ................................................................................. 88 
15.13. Appendix 13: List of Data Displays.............................................................. 89 
15.13.1. Data Display Numbering .............................................................. 89 
15.13.2. Mock Example Shell Referencing ................................................ 89 
15.13.3. Deliverables ................................................................................. 89 
15.13.4. Study Population Tables .............................................................. 90 
15.13.5. Study Population Figures ............................................................. 94 
15.13.6. Efficacy Tables ............................................................................ 95 
15.13.7. Efficacy Figures ........................................................................... 98 
15.13.8. Safety Tables ............................................................................. 100 
15.13.9. Safety Figures ........................................................................... 127 
15.13.10. Pharmacokinetic Tables ............................................................. 130 
15.13.11. Pharmacokinetic Figures ........................................................... 132 
15.13.12. Pharmacokinetic / Pharmacodynamic Figures ........................... 134 
15.13.13. Health Outcomes Tables ........................................................... 135 
15.13.14. Health Outcomes Figures .......................................................... 137 
15.13.15. ICH Listings ............................................................................... 138 
15.13.16. Non-ICH Listings ........................................................................ 142 
15.14. Appendix 14: Example Mock Shells for Data Displays .............................. 147 
 


 
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1. 
INTRODUCTION 
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Study Report for Protocol 205678: 
Protocol Revision Chronology: 
2017N330177_00 
18-JAN-2018 
Original 
2017N330177_01 
02-APR-2018 
Amendment 01 
The protocol has been amended to address regulatory 
agency advice. The original single arm design with 1 dose 
level (3.4 mg/kg GSK2857916 Q3W) was amended to an 
open-label, randomized, 2-arm study with 2 dose levels by 
including the 2.5 mg/kg Q3W dose. In addition, a new 
exploratory cohort of 25 participants, who will receive a 
lyophilized configuration of GSK2857916, has been added 
to gain clinical experience with the lyophilized 
configuration. To accommodate these main changes, the 
overall sample size and related analytical methods have 
been changed. 
2017N330177_03 
04-SEP-2018 
Amendment 02 
Republishing of protocol amendment 2 2017N330177_02 
(Dated: 30 Aug 2018), which was not distributed outside 
GSK. 
The protocol has been amended to address feedback from 
regulatory agencies, EC/IRB, and investigators. The 
updates include the addition of Exclusion Criteria defining 
the use of high dose steroids, clarification of specific 
timeframe from last treatment required for systemic anti-
myeloma therapy,and increase of QTcF criteria. Additional 
PK sampling timepoints were added to capture the Cmax 
of the free cytotoxic drug (cys-mcMMAF) and to better 
define the kinetics of cys-mcMMAF and the elimination 
phase of ADC and cys-mcMMAF. Soluble BCMA collection 
timepoints were also added to capture the effect of 
GSK2857916 administration on soluble BCMA 
concentrations over time as a marker of pharmacodynamic 
effect. The dose modifications guidelines for GSK2857916 
related Corneal Events clarify dose adjustments for GSK 
Scale Grade 2 events. 
2017N330177_04 
17-DEC-2018 
Amendment 03 
The protocol has been amended to address over-
enrolment in the frozen liquid solution portion of the study. 
Due to the over-enrolment, the primary analysis will be 
based on all randomized participants (anticipated ~200) 
enrolled into the frozen liquid solution arms. In addition, a 
sensitivity analysis based on the first 130 participants will 
be performed to account for the original design. 


 
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8 
Protocol Revision Chronology: 
TMF-13990464 
19-Nov-2021 
Amendment 06 
The protocol has been amended to introduce the approved 
standard language for belantamab mafodotin studies 
implementing PACT 
1.1. 
RAP Amendments  
Revision chronology:  
RAP Section 
Amendment Details 
Reporting and Analysis Plan_Study205678_Final_V1 [02-MAY-2019] 
Reporting and Analysis Plan_Study205678_Amendment_Final_V1 [16-JUL-2019] 
Reporting and Analysis Plan_Study205678_Amendment2_Final_V1 [06 Apr 2022] 
RAP Authors/Team Approval 
• 
Update the approvers. 
Section 2.1 Changes to the 
Protocol Defined Statistical 
Analysis Plan  
• 
Updated protocol version and document number 
Section 2.3 Study design 
• 
Updated reference to IA section per PA06. 
Section 3.1 Interim analyses 
• 
Updated protocol version and document number 
Section 3.1.2  Additional 
Comparative Futility Stopping 
Rule Based on Bayesian 
Approach 
• 
Update protocol document number  
Section 3.2 primary analysis 
• 
Updated reference to end of study section per PA06. 
Section 6.2 disposition of 
subjects 
• 
Added analysis regarding visits and assessments Impacted by COVID-
19 Pandemic will be presented 
Section 6.5 Extent of 
exposure 
• 
Added listing of all dose delays due to corneal events (GSK scale) and 
listing of dose delays and associated Eye Disorder Events (CTCAE) 
• 
Added analysis for duration of exposure by response category,  
• 
Added KM curve for time to treatment discontinuation by response 
category and for subject who received at least 3 cycle of the study 
treatment 
• 
Added Swim-lane plot for duration of study treatment for responder 
based on IRC  
Section 7.2.1.5 Progression 
Free survival Table 4 
• 
Updated Adequate baseline assessment definition for Serum FLC 
assay: Involved FLC level  >=10 mg/dL (>=100 mg/L) based on PA06 
Section 7.2.1.7 Overall 
survival 
• 
Updated reference to end of study section per PA06. 
Section 7.2.2 Summary 
measure 
• 
Added a KM curve for Duration of response by dose delay category , 
by response category per IRC. Added Hazard ratio estimate by Pike 
estimator. 
• 
Added a summary for time to best response based on IRC 
• 
Added KM curve for PFS and Overall survival by response category 
per IRC. 


 
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9 
RAP Section 
Amendment Details 
Reporting and Analysis Plan_Study205678_Final_V1 [02-MAY-2019] 
Reporting and Analysis Plan_Study205678_Amendment_Final_V1 [16-JUL-2019] 
Reporting and Analysis Plan_Study205678_Amendment2_Final_V1 [06 Apr 2022] 
Section 8.2.3 Corneal events 
(GSK scale) 
• 
Update protocol document number 
• 
Added new summaries and characteristics tables for Blurred vision, 
Dry Eyes, Ocular symptoms, Visual acuity change , BCVA, Eye 
disorder under #10-72 
• 
Added profile plot for patients with maximum toxicity grade 
• 
Added Bar chart for toxicity grade by cycle 
• 
Added plot for time to recovery post treatment discontinuation for 
corneal exam findings and for keratopathy  
• 
Added plot for visual acuity and corneal findings grade for subject 
experiencing more than 1 corneal events for 2.5 mg/kg arm. 
Section 8.5 Ocular findings 
from ophthalmic exam 
• 
Updated reference to Schedule of activities section per PA06. 
Section 15.7.2.1 Handling of 
Missing and Partial Dates 
• 
Added study end date handling for subjects continuing to PACT as “For 
PACT subjects, subject’s last Visit date will be used as subject’s end of 
study date, wherever required” 
Section 15.12.1 
Abbreviations 
• 
Added description for PACT 
Section 15.13. List of data 
displays 
• 
Added SAC [2] against displays to be produced for End of Study (EoS) 
SAC. 
• 
Added Section for COVID19 displays 
• 
Added F1.00010 F1.00011 F1.00013 T1.11140 F2.00402 T2.0061 
F2.10010 T2.10010 F2.10020 T2.10040 T2.10041 T2.10050 F2.10080 
F2.30305 F2.70033 L3.10010 L3.10011 F3.10031 T3.12030 T3.12461 
T3.12471 T3.12472 T3.12473 T3.12480 T3.12490 T3.12731 T3.12735 
T3.12737 T3.12738 T3.12751 T3.12753 T3.12761 T3.12763 T3.12770 
T3.12771 T3.12772 T3.12773 T3.12774 T3.12781 T3.12791 T3.12793 
T3.12801 T3.12811 T3.12821 T3.12823 T3.12831 T3.12841 T3.12851 
T3.12852 T3.12861 T3.12871 T3.12873 T3.12881 T3.12891 T3.12921 
T3.12931 T3.12941 T3.12951 T3.12961 T3.12971 T3.12981 T3.50013 
T3.50020 T3.50021 T3.50022 F3.50030 F3.53010 F3.53020 T3.60100 
T3.70010 T3.70012 T3.90010 T3.90020 T3.90040 T3.90050 L30.0191  
L8.0102 L8.0103 T8.50070 T8.50080 F1.0082 L1.0082,  
• 
Updated table number for 3.0250 to 3.2051 for Overview of 
Keratopathy Event (CTCAE) , 3.0252 for Overview of Dry Eye Event 
(CTCAE),3.253 for Overview of Blurred Vision Event (CTCAE) 
• 
Updated table title for T3.1280 to Logistic Regression Analysis of 
Possible Risk Factors for Developing Corneal Events Grade >=2 (GSK 
Scale 
• 
Corrected table number for Shift in Corneal Epithelium Findings from 
Baseline to Worst Post-Baseline to 3.0852 based on primary_01 RE 
• 
Per team discussion, updated programming note for Table 3.0710 . 
Removed “In the current footnote, replace ‘<=25000 ng/mL’ with 
‘<=500000 ng/mL’. Added “Replace ‘Negative, Conclusive’ and 


 
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10 
RAP Section 
Amendment Details 
Reporting and Analysis Plan_Study205678_Final_V1 [02-MAY-2019] 
Reporting and Analysis Plan_Study205678_Amendment_Final_V1 [16-JUL-2019] 
Reporting and Analysis Plan_Study205678_Amendment2_Final_V1 [06 Apr 2022] 
‘Negative, Inconclusive’ rows with ‘Negative’ ” . 
RAP Authors/Team Approval 
• 
Update the approvers required and method for approval per 
SOP_54838 (6.0). 
Section 4 Analysis 
Population 
• 
Clarified that same participant enrolled more than once will be counted 
only once based on the last randomization number 
Section 5.1 Study Treatment 
Display Description 
• 
Fixed the error in code labelling and made minor format changes. 
Section 5.3.2. Examination of 
Subgroups 
• 
Added a subgroup Baseline renal impairment status per eGFR 
(ml/min/1.73 m2), which will be included in the existing forest plot for 
ORR.  
• 
Change the wording “Caucasian’ to ‘White’ to be consistent with CRF.  
Section 6.3 Demographic 
and Baseline Characteristics  
• 
Added ‘number of prior lines of therapy’ to the summary table of 
disease characteristics at screening. 
Section 8.1 Adverse Event 
Analysis 
• 
Fixed the typo ‘dose delay’ to ‘permanent discontinuation of study 
treatment’ for AE overview table. 
Section 8.2 Adverse events 
of special interest 
• 
Per team decision: replace the ‘corneal event (CTCAE)’ with ‘eye 
disorder (CTCAE)’; remove the displays associated with corneal event 
(CTCAE); add Section 8.2.2 to specify displays associated with eye 
disorder (CTCAE).  
Section 8.2.3 Corneal events 
(GSK scale) 
• 
Added clarifying edits and fixed typos. 
Section 8.5 Ocular findings 
from ophthalmic exam  
• 
Per team decision: 1) added the shift table from baseline to worst post-
baseline by eye (R/L) for Schirmer’s Test and Tear Break-up Time; 2) 
remove the analyses related to refraction (spherical equivalent) due to 
data collected in text field. 
• 
Added clarifying edits and fixed typos. 
Section 15.6.2  
• 
Clarify the definition of ‘Duration of Exposure’.  
Section 15.6.4  
• 
Replace the ‘corneal event (CTCAE)’ with ‘eye disorder (CTCAE)’ 
Section 15.8.2 
• 
Clarified that ECG displays will be based on central reading unless 
otherwise specified, 
Section 15.13. Appendix 13: 
List of Data Displays 
• 
Remove the displays associated with corneal event (CTCAE): 
T3.0190/3.0210/3.0211/3.0230/3.0240/3.0260 
• 
Replace/add displays associated with eye disorder (CTCAE) as 
specified in Section 8.2.2: T3.0170-3.0174, T3.0180-3.0184, T3.0200-
3.0204, T3.0250-3.0255, T3.0950-3.0954, 3.1320-3.1324, 
L1.0290/1.0300. 
• 
For corneal event (GSK scale), add tables 3.0911/3.1330/3.1331; 
remove Table 3.0390/3.0400 
• 
For visual acuity (GSK scale), add table 3.0912. 
• 
For refraction (spherical equivalent), remove table 3.0750, and figures 


 
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11 
RAP Section 
Amendment Details 
Reporting and Analysis Plan_Study205678_Final_V1 [02-MAY-2019] 
Reporting and Analysis Plan_Study205678_Amendment_Final_V1 [16-JUL-2019] 
Reporting and Analysis Plan_Study205678_Amendment2_Final_V1 [06 Apr 2022] 
3.0010/3.0011. 
• 
Add shift table for Schirmer’s Test and Tear Break-up Time as 
specified in Section 8.5: T3.1340/3.1350 
• 
Updates the displays for QLQ-My20: T8.0080/8.0081)  
• 
Made clarifying edits in title/footnote, update delivery priority, and fixed 
typos in various mock shells to incorporate comments/decision 
following dry run reviews.  
Section 15.14. Appendix 14: 
Example of Mock Shells 
• 
Add mock shell Safe_T4b, Safe_T9a, Safe_T21, and Safe_T22. 
• 
Made clarifying edits in title/footnote, and fixed typos in various mock 
shells to incorporate comments from dry run reviews. 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan  
There were no changes or deviations to the originally planned statistical analysis 
specified in the protocol amendment 6 GSK Document Number TMF-13990464  (Dated: 
19-Nov-2021).  
2.2. 
Study Objective(s) and Endpoint(s)  
Objectives 
Endpoints 
Primary Objectives 
Primary Endpoints 
• 
To evaluate the clinical efficacy of 2 
doses of GSK2857916 in participants 
with relapsed/refractory multiple 
myeloma. 
• 
ORR, defined as the percentage of participants with a 
confirmed partial response (PR) or better (i.e., PR, very 
good partial response [VGPR], complete response [CR] 
and stringent complete response [sCR]), according to the 
2016 International Myeloma Working Group (IMWG) 
Response Criteria by Independent Review Committee 
(IRC). 
Secondary Objectives 
Secondary Endpoints 
• 
To further evaluate the clinical 
measures of efficacy of GSK2857916 
in participants with RRMM 
• 
ORR, defined as the percentage of participants with a 
confirmed partial response (PR) or better, according to 
the 2016 International Myeloma Working Group (IMWG) 
Response Criteria by investigator assessment 
 
• 
Clinical benefit rate (CBR), defined as the percentage of 
participants with a confirmed minimal response (MR) or 
better according to the 2016 International Myeloma 
Working Group (IMWG) Response Criteria  
 
• 
Duration of response (DoR), defined as: the time from 
first documented evidence of PR or better until the 
earliest date of documented disease progression (PD) 


 
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205678 
 
12 
Objectives 
Endpoints 
per IMWG; or death due to PD occurs among participants 
who achieve an overall response, i.e., confirmed PR or 
better. 
 
• 
Time to response, defined as the time between the date 
of randomization and the first documented evidence of 
response (PR or better). 
 
• 
Progression-free survival, defined as the time from 
randomization until the earliest date of documented 
disease progression (PD) per IMWG, or death due to any 
cause. 
 
• 
Time to progression, defined as the time from 
randomization until the earliest date of documented PD 
per IMWG, or death due to PD. 
 
• 
Overall survival, defined as the time from randomization 
until death due to any cause. 
• 
To evaluate the safety of 
GSK2857916 in participants with 
RRMM. 
• 
The safety profile of GSK2857916 will be evaluated in 
participants with RRMM as assessed through: standard 
clinical and laboratory tests (haematology and chemistry, 
physical examination, vital sign measurements, and 
diagnostic tests) through the collection of adverse events 
(AEs) and serious adverse events (SAEs) 
• 
AE of special interest 
• 
ocular findings on ophthalmic exam  
• 
To evaluate the pharmacokinetic 
profile of GSK2857916 
• 
Plasma concentrations of GSK2857916 (ADC, total mAb, 
and cys-mcMMAF) 
• 
Derived pharmacokinetic parameter values (e.g., AUC, 
Cmax, tmax, t½), as data permit. 
• 
To assess anti-drug antibodies 
(ADAs) against GSK2857916 
• 
Incidence and titers of ADAs against GSK2857916 
• 
Participant self-reported symptomatic 
adverse effects by evaluation of 
tolerability of GSK2857916 
• 
Symptomatic adverse effects and related impacts as 
measured by the PRO-CTCAE, NEI-VFQ-25 and OSDI 
• 
To evaluate disease and treatment 
related symptoms and impact on 
function and health-related quality-of-
life 
• 
Health-related quality-of-life as measured by the EORTC 
QLQ-C30 and EORTC QLQ-MY20 
Exploratory Objectives 
Exploratory Endpoints 
• 
To explore the relationship between 
clinical response and other biologic 
characteristics including BCMA 
expression on tumor cells and sBCMA 
concentrations  
• 
Determine BCMA expression levels and other markers on 
malignant cells, serum sBCMA levels, and evaluate the 
relationship of these factors to clinical response 
• 
To investigate the relationship 
between genetic variants in the host 
and response to GSK2857916  
• 
Possible relationship between host genetic variation and 
response to GSK2857916 
• 
To evaluate disease and treatment 
• 
Qualitative telephone interview(s) 


 
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13 
Objectives 
Endpoints 
related symptoms and impact on 
function and health-related quality-of-
life 
• 
To explore exposure-response 
relationships between GSK2857916 
exposure and clinical endpoints 
• 
Explore relationships between GSK2857916 exposure 
(e.g., dose, dose intensity, concentration, Cmax, or AUC) 
and clinical endpoints (e.g., response, corneal event), if 
data permit 
• 
To assess Minimal Residual Disease 
(MRD) in participants who achieve 
≥VGPR or better 
• 
Minimal Residual Disease (MRD) negativity rate, defined 
as: the percentage of participants who are MRD negative 
by Next Generation Sequencing (NGS). 
• 
To assess the safety, efficacy, 
immunogenicity, and 
pharmacokinetics of GSK2857916 in 
a lyophilized configuration (n = 
approximately 25 participants) 
• 
AEs, clinical and laboratory assessments; Descriptive 
analyses of ORR, duration of response, time to response, 
time to progression, overall response; incidence and titers 
against GSK2857916; plasma concentrations of 
GSK2857916 (ADC, total mAb, and cys-mcMMAF) and 
derived pharmacokinetic parameters, if data permit 
• 
Ocular sub-study objective 
• 
To evaluate the effect of topical 
corticosteroids on corneal findings in 
approximately 30 participants who will 
receive monocular topical 
corticosteroids for the first 4 cycles 
• 
Description of differences in corneal findings in each eye 
based on ophthalmic examinations (participant-level). 
• 
Abbreviations: IV = intravenous; Q3W: once every 3 weeks; RRMM = relapsed refractory multiple 
myeloma; BCMA = B-cell maturation antigen; MMAF = monomethyl auristatin-F; MRD = minimal 
residual disease; NGS = Next Generation Sequencing; ORR = overall response rate; CI = confidence 
interval; CR = complete response; VGPR = very good partial response; PR = partial response; PFS = 
progression free survival; AUC = area under the curve; Cmax = maximum observed concentration; 
tmax = time to maximum observed concentration; t½ = terminal phase half-life; PRO-CTCAE = Patient 
Reported Outcomes-Common Terminology Criteria for Adverse Events; NEI-VFQ-25 = National Eye 
Institute Visual Functioning Questionnaire 25; OSDI = Ocular Surface Disease Index; EORTC = 
European Organisation for Research and Treatment of Cancer; QLQ-C30 = Quality of Life 
Questionnaire 30-item Core module; FLC =  free light chain; SCT = stem cell transplant; QLQ-MY20 = ; 
Quality of Life Questionnaire 20-item module for MM; QTcF = QT interval corrected by Fridericia's 
formula; HIV = human immune deficiency virus; RNA = ribose nucleic acid. 


 
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14 
2.3. 
Study Design 
Overview of Study Design and Key Features 
Design 
Features 
• 
GSK2857916 Frozen Configuration Cohorts 
o Population: Subjects with relapsed/refractory MM (130 subjects (65/arm) 
as planned) 
o Objective: evaluate the efficacy and safety of 2 doses of GSK2857916 in 
participants with RRMM who have received at least 3 prior lines of anti-
myeloma therapy, have failed an anti-CD38 antibody, and are refractory 
to PI and IMiDs. 


 
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15 
Overview of Study Design and Key Features 
• 
Independent GSK2857916 Lyophilized Configuration Cohort 
o Population: Subjects with relapsed/refractory MM (at least 25 subjects) 
o Objective: To assess the safety, efficacy, immunogenicity, and PK of 
GSK2857916 in a lyophilized configuration. 
• 
Ocular Sub-Study 
o Population: Subjects with relapsed/refractory MM (up to 30 subjects (15 
subjects each dose)) 
o Objective: evaluate the effect of topical corticosteroids on corneal 
findings in subjects who will receive monocular topical corticosteroids for 
the first 4 cycles and sign an optional ICF. 
Dosing 
• 
GSK2857916 Frozen Configuration Cohorts 
o GSK2857916 will be administered at a calculated dose of 2.5 mg/kg or 3.4 mg/kg 
as an IV infusion over at least 30 minutes at the study sites. 
o Independent GSK2857916 Lyophilized Configuration Cohort  
o GSK2857916 will be administered at a calculated dose of 3.4 mg/kg as an IV 
infusion over at least 30 minutes at the selected study sites when the lyophilized 
configuration becomes available. 
o Lyophilized configuration cohort will be initiated at 2.5 mg/kg  if the results of the 
IA indicate that 3.4 mg/kg should not be continued. . 
Time & 
Events 
• 
Refer to Appendix 2: Schedule of Activities 
Treatment 
Assignment 
• 
This is a two-arm, randomized, multi-center, open-label study for GSK2857916 frozen 
configuration cohort. 
• 
For independent lyophilized cohort, there is only one dose group 
Interim 
Analysis 
GSK2857916 Frozen Configuration Cohorts 
• 
One interim analysis (IA) is planned for the primary endpoint ORR after approximately 
25 participants per arm are evaluable for response. Further details can be referred to 
in Section 3 of RAP and Section 4.1 of the protocol (Version: GSK Document Number 
TMF-13990464 ). 
 
2.4. 
Statistical Hypotheses / Statistical Analyses 
Study 205678 is designed to provide evidence with respect to ORR to either support the 
null hypothesis, H0: ORR ≤15%, or reject H0 in favor of the alternative hypothesis, 
H1: ORR≥33%.  The hypothesis testing will be performed within each arm separately.  
No hypothesis testing for comparing ORR between the two arms will be performed. 


 
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16 
3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
Details of the interim analysis can be referred to in Protocol Amendment 6 (GSK 
Document Number. TMF-13990464  ) and the IDMC charter. Details of the planned 
displays are provided in Appendix 13: List of Data Displays. 
3.1.1. 
Futility Stopping Rule Based on Group Sequential Design 
For each arm (2.5 mg/kg or 3.4 mg/kg), a single futility IA is planned for the primary 
endpoint ORR after approximately 25 participants (~38% information fraction) per arm 
are evaluable.  A user-defined gamma spending function (γ=1.1) [Hwang, 1990] was used 
as a beta-spending function to determine the non-binding futility boundary (as 
implemented in East 6.4).  With this β-spending function, the stopping boundary in IA is 
identified as 0.16 on the proportion scale (4 responders out of 25 participants), which is 
close to the historical control of 0.15. The spending function and associated boundary 
were chosen to ensure good operating characteristics, specifically, the type 1 error and 
power are well controlled.  
A two-step approach is used to identify the futility stopping rule based on a group 
sequential design under the assumption of exact binomial distribution.  
First, as described in Section 3.1.1.1, an initial design based on the assumption of normal 
approximation of binomial proportion was identified by East 6.4. 
The interim futility and primary efficacy analysis boundaries were then converted to 
number of responders needed in 25 participants per arm who are evaluable at IA and the 
65 participants per arm initially planned at the primary analysis. 
With a total sample size of 100 participants per arm and an IA with approximately 25 
participants per arm, the same futility boundary (≤ 4 responders out of 25 participants) 
will still apply with a user-defined gamma spending function (γ=5.4). For the primary 
analysis, the boundary for claiming efficacy is the minimum number of responders 
required for the lower bound of the two-sided 97.5% exact C.I. to exceed 15% (i.e. 24 
responders for sample size of 100 per arm).  
Statistical properties of the group sequential design with sample sizes of 65, and 100 per 
arm are summarized in Table 1. 


 
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17 
Table 1 
Probabilities of Crossing Boundaries at the Interim or Primary ORR 
Analysis based on Group Sequential Design 
Look 
Sample 
Size (per 
arm) 
Boundaries 
Cumulative Boundary Crossing 
Probabilities 
# of Responders 
Under H0 
Under H1 
Interim (futility) 
25 
≤4 
68.21% 
4.96% 
Primary 
(Efficacy) 
65 
17 
1.23% 
88.00% 
100 
24 
0.97% 
93.70% 
Note: The Cumulative Boundary Crossing Probabilities are calculated based on exact binomial distribution 
theoretically. 
 
3.1.1.1. Operating Characteristics of the Stopping Rules for Futility 
The following assumptions were made in the estimation of the required sample size: 
• Normal approximation of binomial proportion 
• A response rate of ≥33% in the BCMA arm and ≤15% for the historical control 
• A 1.25%, one-sided risk of erroneously claiming superiority of the BCMA arm, in 
the presence of no true underlying improvement 
• A ~90% chance of rejecting the null hypothesis when the alternative hypothesis is 
true 
 
An IA after approximately 38% of information is available (i.e., approximately after 25 
participants out of originally planned 65 participants per arm are evaluable for IA), with a 
futility rule based on a gamma spending function. 
The operating characteristics were refined using simulation to account for the within arm 
futility rule and the comparative futility rule. Based on the simulation results with the 
originally planned sample size of 65 participants per arm, there is 86.90% power to reject 
the null hypothesis within each arm with a 1-sided type I error of 1.23%. 
Due to over enrolment, it is estimated that approximately 200 participants (~100 per arm) 
will be randomized to the frozen liquid solution. At the primary analysis, the null 
hypothesis will be rejected if the lower bound of 2-sided 97.5% exact C.I. exceeds the 
historical control rate of 15%.  
With no change to the planned IA (i.e., approximately after 25 participants/arm are 
evaluable for IA, and same futility boundary), simulation results show that there is 
92.38% power to reject the null hypothesis within each arm with a 1-sided type I error of 
0.97% for 100 participants per arm as shown in Table 1. 
 


 
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18 
3.1.2. 
Additional Comparative Futility Stopping Rule Based on 
Bayesian Approach 
If both arms pass the futility boundaries based on group sequential design described 
above, posterior probability of observing a better RR in one arm relative to the other will 
be calculated. If such a probability is at least 97.5%, then the treatment arm with lower 
RR will be dropped due to lack of efficacy. This additional guidance was put in to allow 
for dropping an arm with substantially inferior response rates (e.g. absolute difference > 
28%). 
To calculate the posterior probability, a non-informative Beta prior (0.025,0.1) will be 
used for each arm. Details about calculating the posterior probabilities are provided in 
Appendix 12 of the protocol amendment 3 (GSK Document Number TMF-13990464 ).  
Statistical properties for different scenarios based on both futility rules are summarized in 
Table 2. 
Table 2 
Probabilities of Stopping for Futility at the Interim or Claiming 
Efficacy at the Primary ORR Analysis based on Both Futility Rules 
Scenarios 
Participants 
per arm 
Response Rate 
Futility Stopping 
Boundary Crossing 
Probabilities at IA [1] 
Probabilities of 
Claiming Efficacy at 
Primary [1] 
Arm 1 [2] 
Arm 2 [2] 
Arm 1 [2] 
Arm 2 [2] 
Arm 1 [2] 
Arm 2 [2] 
1 
65 
33% 
60% 
53.59% 
0.01% 
44.83% 
99.99% 
2 
65 
33% 
45% 
16.95% 
0.47% 
77.94% 
99.49% 
3 [3] 
65 
33% 
33% 
6.33% 
6.33% 
86.90% 
86.92% 
4 
65 
33% 
25% 
5.09% 
23.83% 
87.89% 
42.39% 
5 
65 
33% 
20% 
4.97% 
44.59% 
87.98% 
12.52% 
6 
65 
33% 
15% 
4.96% 
69.99% 
87.99% 
1.20% 
7 
65 
33% 
10% 
4.96% 
90.85% 
87.99% 
0.01% 
8 [4] 
65 
15% 
15% 
68.22% 
68.22% 
1.23% 
1.24% 
9 
100 
33% 
60% 
53.59% 
0.01% 
46.11% 
99.99% 
10 
100 
33% 
45% 
16.95% 
0.47% 
82.09% 
99.53% 
11 [3] 
100 
33% 
33% 
6.33% 
6.33% 
92.38% 
92.39% 
12 
100 
33% 
25% 
5.09% 
23.83% 
93.57% 
53.93% 
13 
100 
33% 
20% 
4.97% 
44.59% 
93.68% 
15.46% 
14 
100 
33% 
15% 
4.96% 
69.99% 
93.70% 
0.94% 
15 
100 
33% 
10% 
4.96% 
90.85% 
93.70% 
0.003% 
16 [4] 
100 
15% 
15% 
68.22% 
68.22% 
0.97% 
0.97% 
Note:  
[1] The Boundary Crossing Probabilities are calculated based on 10,000,000 simulations using R program.  
[2] Arm 1 and Arm 2 in the table just represent two different treatment arms and are not necessarily refers to 3.4 
mg/kg and 2.5 mg/kg, respectively.  
[3] The power is shown in Scenario 3, and 11 as 86.90% and 92.38% for sample size of 65, and 100 respectively. 
[4] The type I error is shown in Scenario 8, and 16 as 1.23%, and 0.97% for sample size of 65, and 100 respectively. 


 
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19 
3.2. 
Primary Analyses 
The planned primary analyses will be performed after the completion of the following 
sequential steps: 
1. The study reaches 6 months after the last participant in frozen liquid configuration is 
randomized in the study. 
2. All required database cleaning activities have been completed and database release 
(DBR) and database freeze (DBF) have been declared by Data Management. 
3. All criteria for unblinding the randomization codes have been met.  
4. Randomization codes have been distributed according to RandAll NG. 
 
An updated analysis for OS will be performed at end of study as defined in Section 4.6 of 
protocol (Version: GSK Document Number TMF-13990464 ). 
 
4. 
ANALYSIS POPULATIONS 
 
Population 
Definition / Criteria 
Analyses Evaluated 
All Screened 
• 
All participants who sign the ICF to 
participate in the study. 
• 
Study Population 
Enrolled 
• 
All participants who passed screening. Note 
screening failures (who never passed 
screening even if rescreened) and 
participants screened but never enrolled 
into the study (Reserve, Not Used) are 
excluded from the Enrolled population as 
they did not enter the study. Same 
participant enrolled more than once will be 
counted only once based on the last 
randomization number. 
• 
This population will be based on the 
treatment the participant was randomized 
to. 
• 
Study Population 
Frozen 
liquid 
configuration 
Intent-to-
Treat 
(ITT) 
• 
All randomized participants whether or not 
randomized treatment was administered. 
• 
This population will be based on the 
treatment the participant was randomized 
to. 
• 
Any participant who receives a treatment 
randomization number will be considered to 
have been randomized. 
Same participant receiving multiple 
randomization numbers will be counted only 
once using the last randomization number. 
• 
Study Population 
• 
Efficacy 
• 
EORTC QLQ-C30 
and EORTC QLQ-
MY20 
Efficacy  
• 
Efficacy population will consist of first 130 
ITT participants whether or not randomized 
treatment was administered. This 
population will be based on the treatment to 
which the participant was randomized and 
will be used for sensitivity analysis of 
• 
Selected efficacy  


 
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Population 
Definition / Criteria 
Analyses Evaluated 
primary and selected secondary efficacy 
endpoints. 
Evaluable • 
All participants who have at least two doses 
of study treatment and have completed at 
least one disease assessment after the 
second dose,  or progressed or died or 
discontinued treatment due to other 
reasons.  
• 
Futility analyses at IA  
Safety 
• 
All randomized participants who received at 
least one dose of Frozen liquid study 
treatment. 
• 
This population will be based on the 
treatment the subject actually received (first 
dose). 
• 
Safety 
• 
PRO-CTCAE, NEI-
VFQ-25 and OSDI. 
Ocular 
Sub-
Study  
• 
All randomized participants to ocular sub-
study who received at least one dose of 
study treatment.  
• 
This population will be used to evaluate the 
effect of topical corticosteroids on corneal 
events/findings in approximately 30 
participants who will receive monocular 
topical corticosteroids for the first 4 cycles 
• 
Corneal 
events/findings 
Lyophilized 
configuration 
Lyo  
• 
All randomized participants who receive at 
least 1 dose of lyophilized study treatment. 
• 
All analysis other 
than PK 
Full Analysis 
• 
All participants included in either ITT or Lyo 
population  
• 
This population will be based on the 
treatment the participant was randomized to 
• 
Study population 
• Efficacy 
• 
EORTC QLQ-C30 
and EORTC QLQ-
MY20 
Full Safety 
• 
All participants who receive at least 1 dose 
of study treatment (frozen liquid or 
lyophilized). 
• 
This population will be based on the 
treatment the subject actually received (first 
dose). 
• 
Safety 
• 
PRO-CTCAE, NEI-
VFQ-25 and OSDI. 
Full Pharmacokinetic 
(PK) 
• 
All participants in the Full Safety population 
who had at least 1 non-missing PK 
assessment (Non-quantifiable [NQ] values 
will be considered as non-missing values). 
• 
PK 
Note: Refer to Appendix 13: List of Data Displays which details the population used for each display being generated 
in the final version of the RAP.  
 
 
 
 
 
 
 


 
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4.1. 
Protocol Deviations 
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be 
summarised and listed. 
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan [Version 4.0, dated 
22Mar2022].  
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 will 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 
Treatment Group Descriptions 
RandAll NG 
Data Displays for Reporting  
Code 
Description 
Description 
Order in 
TLF  
B 
2.5 mg/kg frozen liquid 
solution of GSK2857916 
2.5 mg/kg  
1 
A 
3.4 mg/kg frozen liquid 
solution of GSK2857916 
3.4 mg/kg 
2 
C 
lyophilized configuration of 
GSK2857916 
3.4 mg/kg Lyo, actual dose level subject to IA 
result  
3 
L 
receive topical 
corticosteroids in left eye 
only 
“3.4 mg/kg treated eye” for the treated eyes of 
participants in 3.4 mg/kg group (frozen liquid);  
 
“3.4 mg/kg untreated eye” for the untreated eyes 
of participants in 3.4 mg/kg group (frozen liquid) 
 
“2.5 mg/kg treated eye” for the treated eyes of 
participants in 2.5 mg/kg group (frozen liquid);  
 
“2.5 mg/kg untreated eye” for the untreated eyes 
of participants in 2.5 mg/kg group (frozen liquid). 
4 
 
 
5 
 
 
6 
 
 
7 
 
R 
receive topical 
corticosteroids in right eye 
only 
 
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 subjects who did not receive study treatment during the 
study, baseline will be defined as the latest, non-missing collected value. 
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. 
For ECG analyses, subject level baseline is defined as the mean of triplicate baseline 
assessments. 
Unless otherwise stated, if baseline data is missing, no derivation will be performed, and 
baseline will be set to missing. 


 
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5.3. 
Examination of Covariates, Other Strata and Subgroups 
5.3.1. 
Covariates and Other Strata 
The list of strata may be used in descriptive summaries and statistical analyses, some of 
which may also be used for subgroup analyses. Additional strata of clinical interest may 
also be considered. 
Category 
Details 
Number of 
prior lines of 
therapy 
≤4, >4 
Cytogenetic 
risk  
high risk, Other (non-high risk - all others) 
NOTES: A subject is considered as high risk if the subject has any of the following cytogenetics: t(4;14), 
t(14;16), and 17p13del. 
5.3.2. 
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. 
• 
If the percentage of subjects is small within a particular subgroup, then the subgroup 
categories may be refined prior to unblinding the trial. 
Subgroup 
Categories  
Age Group (at screening) 
18 to <65, 65 to < 75, ≥ 75  
Sex 
Male, Female 
Ethnic Background 
White, Black, Other 
ISS Staging at Screening 
I, II, III, Other (Unknown or Missing) 
Baseline renal impairment status 
per eGFR (ml/min/1.73 m2) 
Normal (≥ 90), Mild (≥ 60, < 90), Moderate (≥ 30, < 60), Severe 
(≥ 15, < 30) 
Number of prior lines of therapy 
<=4, >4 
Type of myeloma 
IgG, Non-IgG 
Cytogenetics Risk [1] 
High, Other (non-high risk - all others) 
Refractory to prior anti-cancer 
therapy 
Any Proteasome Inhibitor (PI) 
Bortezomib 
Carfilzomib 
Ixazomib 
Any Immunomodulator (IMiD) 
Thalidomide 
Lenalidomide 
Pomalidomide 
Any Monoclonal Antibodies 
Elotuzumab 
Isatuximab 
Daratumumab 
       Daratumumab alone [2] 


 
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Subgroup 
Categories  
       Daratumumab in combination [3] 
PI+IMiD 
Daratumumab+PI+IMiD 
Penta-refractory [4] 
NOTES: 
[1] A subject is considered as high risk if the subject has any of the following cytogenetics: t(4;14), t(14;16), 
and 17p13del. 
[2] Defined as prior CTX regimen with Daratumumab as the only drug in the regimen. 
[3] Defined as prior CTX regimen with Daratumumab and other drugs. 
[4] Defined as refractory to: Bortezomib, AND Carfilzomib AND Lenalidomide AND Pomalidomide AND 
Daratumumab. 
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 
Section 15.3 
Appendix 3: Assessment Windows 
Section 15.4 
Appendix 4: Study Phases and Treatment Emergent Adverse Events 
Section 15.5 
Appendix 5: Data Display Standards & Handling Conventions 
Section 15.6 
Appendix 6: Derived and Transformed Data 
Section 15.7 
Appendix 7: Reporting Standards for Missing Data 
Section 15.8 
Appendix 8: Values of Potential Clinical Importance 
 


 
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6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Study Population Analyses 
The study population analyses will be based on the “Intent-to-Treat” population for 
frozen liquid cohort alone, and ‘Full Analysis’ population for frozen liquid cohort plus 
lyophilized cohort (side-by-side presentation). If needed, the study population analyses 
for lyophilized cohort alone will be based on the “Lyo” population.   
Unless otherwise specified, no ‘Total’ column will be provided for study population 
outputs. 
Study population analyses including analyses of subject’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
subsequent 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 13: 
List of Data Displays. 
6.2. 
Disposition of Subjects 
A summary of the number of subjects in each of the analysis populations described in 
Section 4 will be provided (for primary analysis, Evaluable population will not be 
included). In addition, the number of subjects enrolled by centre will be summarized by 
dose level using the “Enrolled” population. A separate summary for exclusions from each 
study population will be displayed (for primary analysis, Evaluable population will not be 
included). A listing of subjects excluded from analysis populations will also be provided. 
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.  
A listing of subjects with visits and assessments Impacted by the COVID-19 Pandemic 
will be presented.  A stacked bar chart depicting visits impacted by COVID-19 will be 
presented. 
 
6.3. 
Demographic and Baseline Characteristics 
The demographic characteristics (e.g., age, race, ethnicity, sex, baseline height, and 
baseline body weight and baseline BMI) will be summarized and listed. Age, height, 


 
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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 will be summarized and listed. 
Disease history and characteristics (e.g. time since initial diagnosis in years, stage at 
initial diagnosis, date of initial diagnosis) at initial diagnosis and screening will be listed. 
Separate summaries of disease characteristics at initial diagnosis and screening will be 
provided. Disease characteristics at screening, including stage, type of multiple myeloma, 
number of prior lines, and types of therapy, myeloma light chain and myeloma 
immunoglobulin, extramedullary disease, lytic bone lesion, and genetic characteristics 
(including high cytogenetic risk) will be summarized and listed. 
Medical conditions collected at screening will be listed and will be summarized by past 
and current and by cancer-related and non-cancer related categories.  
Substance use, including smoking history and alcohol use will be summarized. 
Prior anti-cancer therapy will be coded using GSK Drug coding dictionary, then 
summarized by type of therapy and listed. A listing of prior anti-cancer therapy will show 
the relationship between ATC Level 1, Ingredient, and verbatim text. A summary of the 
best response to the most recent prior anti-cancer therapy will be provided. A summary of 
the number of prior anti-cancer therapy regimens will also be produced.  
Prior anti-cancer therapy for multiple myeloma subjects will also be summarized by type 
of therapy, and drug class. A summary of multiple myeloma subjects’ refractory to prior 
anti-cancer therapy by drug class will be provided.  
Anti-cancer radiotherapy will be listed. Prior cancer and non-cancer related surgeries will 
be summarized. Prior and on treatment cancer and non-cancer related surgeries will be 
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 described in Section 6.5 ‘Extent of Exposure’. 
6.5. 
Extent of Exposure 
Extent of exposure to GSK2857916 will be summarized. 
The number of cycles administered to study treatment will be summarised with mean, 
median, standard deviation, minimum, and maximum.  
Dose delivered per cycle (mg/kg/cycle) will be summarized using mean, median, 
standard deviation, minimum, and maximum by cycle and overall. The dose intensity 
(mg/kg/3 weeks), which is calculated as the cumulative actual dose (mg/kg) divided by 
expected duration of exposure in 3 weeks (last infusion date – first infusion date + 


 
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21)/21), will also be summarized. A by subject summary listing of data on exposure to all 
study treatments will be produced. 
Dose reductions will be summarised by number of reductions and reasons for reductions.  
Dose delays will be summarised by number of delays, reasons for the delays, and delay 
duration (days). The number and percentage of the delays for intervals of 1-21, 22-42 and 
>42 days will be computed. Primary reasons for dose reductions and dose delays will also 
be summarized by cycle. Listing of all dose delays due to corneal events (GSK scale) and 
listing of dose delays and associated Eye Disorder Events (CTCAE) will be produced. 
Duration of delays is defined as period from the expected start date of dose to actual start 
date of current dose. Calculation: (actual start date of current dose - expected start date of 
dose). Expected start date of dose = actual start date of previous dose + 21. 
The summaries of dose modifications will be provided. All the dose reductions, dose 
escalations, infusion interruptions, incomplete infusions and dose delays will be listed. 
A plot showing the number and percentage of subjects treated at different dose levels 
over time will be provided. 
The duration of exposure to study treatment (from first day to last day of treatment) will 
be calculated and summarized using mean, median, standard deviation, minimum, and 
maximum. A horizontal bar graph of duration of treatment will be produced that displays 
duration of treatment in months for each subject. Summary of duration of exposure by 
response category based on IRC will be presented. 
A Kaplan Meier curve for time to treatment discontinuation by Response Category Based 
on IRC, and a Kaplan Meier curve for time to treatment discontinuation for subjects who 
have received at least 3 cycles of the study treatment will be presented.  
Swim-lane Plot of duration of study treatment for responder based on Independent 
Reviewer-Assessed Response will be produced. 
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.  
In the summary of concomitant medications, each subject is counted once within each 
unique ingredient. For example, if a subject takes Amoxycillin on two separate occasions, 
the subject is counted only once under the ingredient “Amoxycillin”. In the summary of 
concomitant medications, the ingredients will be summarized by the base only, using 
CMBASECD and CMBASE. Note: In order to be considered a concomitant medication, 
the concomitant medication must have been taken at some point during the on-treatment 
window. 


 
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Prophylactic medication for infusion-related reactions and prophylactic topical eye 
medications will be summarized by drug class and drug name and listed separately. In 
addition, the percentage of duration of exposure (see Section 15.6.2 for definition) that 
was on prophylactic steroid eye drop use will also be summarized. 
Blood products or blood supportive care products with onset date within the on-treatment 
window will be included in the summary tables. The frequency and percentage of 
subjects using blood products and blood supportive care products after the start of study 
medication will be provided. Supporting listings will also be provided. 
6.7. 
Subsequent Anti-Cancer Therapies 
The number and percentage of subjects that received chemotherapy, immunotherapy, 
hormonal therapy, biologic therapy, radioactive therapy, small molecule targeted therapy, 
as subsequent anti-cancer therapy will be summarized. Time from study treatment 
discontinuation to the first post study treatment anti-cancer therapy will also be included 
in this summary table, if available. 
Follow-up anti-cancer therapy will be coded using GSK Drug coding dictionary, then 
summarized by ingredient. A listing of the type of follow-up anti-cancer therapy received 
(chemotherapy, immunotherapy, hormonal therapy, biologic therapy, radioactive therapy, 
and small molecule targeted therapy) for each subject will be provided. 


 
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7. 
EFFICACY ANALYSES 
The efficacy analyses will be based on the ‘Intent-to-Treat’ or ‘Efficacy’ population for 
frozen liquid cohort alone, and ‘Full Analysis’ population for frozen liquid cohort plus 
lyophilized cohort (side-by-side presentation). If needed, the efficacy analyses for 
lyophilized cohort alone will be based on the ‘Lyo’ population. 
Unless otherwise specified, no ‘Total’ column will be provided for efficacy outputs 
7.1. 
Primary Efficacy Analyses 
7.1.1. 
Overall Response Rate (ORR) based on IRC assessment 
ORR, defined as the percentage of participants with a confirmed partial response (PR) or 
better (i.e., PR, very good partial response [VGPR], complete response [CR] and 
stringent complete response [sCR]), according to the 2016 International Myeloma 
Working Group (IMWG) Response Criteria [Kumar, 2016]. ORR based on Independent 
Review Committee (IRC) will be analyzed as the primary endpoint.  
ORR at  primary analysis will be analyzed based on the confirmed responses, which will 
be derived based on the algorithm specified in Table 3.   
Only the assessments from the start of treatment up to the earlier of confirmed disease 
progression or the start of new anti-cancer therapy will be considered. Only new systemic 
anti-cancer drugs taken are considered as anti-cancer therapy (radiotherapy and surgeries 
are not considered as systemic anti-cancer therapy for the purpose of this analysis). 
Subjects with only assessments of Not Evaluable or missing response will be treated as 
non-responders; i.e. they will be included in the denominator when calculating the 
percentage. 
7.1.1.1. Derivation of Confirmed Response  
The derivation of confirmed response shall be based on the algorithm specified in Table 
3. The date of the first of the two consecutive assessments will be used as the date of the 
confirmed response. 
Table 3 
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 


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


 
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# 
Response at the First Time 
Point 
Response at Subsequent 
Disease Assessment1 
Confirmed Response at 
the First Time Point 
assessment 
16 PD due to  
imaging (plasmacytoma or 
bone lesion) 
Any 
 
OR 
No subsequent disease 
assessment 
PD 
17 NE or missing 
Any 
 
OR 
No subsequent disease 
assessment 
NE 
1. Subsequent disease assessment is defined as the next adequate (not missing or NE) disease 
assessment following the first timepoint before (or on the same date of) start of new anti-cancer 
therapy except for confirmation of PD, for which PD or death due to PD after new anti-cancer 
therapy are considered for confirmation of PD. No minimal time interval is required for the 
subsequent disease assessment, but a different sample is required for confirmation. 
2. SD does not need to be confirmed. 
3. PD due to imaging (i.e., plasmacytoma or bone lesion) does not need to be confirmed. 
4. Where criteria are not mutually exclusive, take the first that applies. 
 
7.1.2. 
Summary Measure 
The number and percentage of participants with best overall response (BOR) in the 
following response categories will be summarized by dose level: 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 2-sided 97.5% 
exact CI for ORR will also be provided. Participants with only 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. A list of IRC-assessed response 
at each visit will be listed. 
For subgroup analysis, ORR will be presented using forest plot for the following 
categories: Age, Sex, Ethnic Background, ISS Staging at Screening, Number of prior 
lines of therapy, Type of myeloma, , Refractory to prior anti-cancer therapy, Cytogenetics 
Risk as defined in Section 5.3.2 
A waterfall plot showing the maximum percent reduction from baseline in Serum M-
protein, or Urine M-protein, or difference between two types Serum FLC [Kappa light 
chain (Kappa LC) and Lambda light chain (Lambda LC)] for each subject will be 
produced using by dose level. The plot will be color-coded for M-protein types and 
Serum FLC, etc. Indication of the best overall response will be provided below the plot. 
Only the assessments from the start of treatment up to the start of new anti-cancer therapy 
will be considered. Only new systemic anti-cancer drugs taken are considered as anti-
cancer therapy (radiotherapy and surgeries are not considered as systemic anti-cancer 
therapy for the purpose of this analysis).  
The maximum percent reduction will be plotted in the following hierarchical order:  


 
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[1] Plot Serum M-protein maximum percent reduction from baseline if data is 
available; 
[2] If [1] is not feasible, plot Urine M-protein maximum percent reduction from 
baseline if data is available; 
[3] If both [1] and [2] are not feasible, plot maximum percent reduction from baseline 
for difference between two types of Serum FLC if data is available; 
Difference between two types of Serum FLC  
The percent change from baseline for difference between two types of Serum FLC is 
defined as:  
(post-baseline difference-baseline difference) / baseline difference *100% 
To calculate the difference, the “involved” and “non-involved” light chains must be 
determined at first based on the ratio of non-missing values for Serum Kappa LC protein 
and Serum Lambda LC protein at baseline. 
The detailed algorithm is provided as below: 
• If the baseline ratio of (Kappa LC/Lambda LC)>1.65, then Kappa LC is defined as 
involved FLC, and Lambda LC is defined as non-involved FLC. Then 
o Difference between involved and uninvolved = Kappa LC-Lambda LC 
• If the baseline ratio of (kappa/lambda) <0.26, then Lambda light chain is defined as 
involved FLC, and Kappa light chain is defined as non-involved FLC 
o Difference between involved and uninvolved = Lambda LC-Kappa LC 
• If the baseline ratio of (Kappa LC/Lambda LC) 1.65 and  0.26, then “involved” 
and “non-involved” FLC can not be determined (ratio is normal), and maximum 
percent reduction from baseline for difference between two types of Serum FLC 
won’t be available. 
7.1.3. 
Population of Interest  
ORR at primary analysis will be analyzed using both ITT and Efficacy population for 
frozen liquid cohort, and Lyo population for lyophilized cohort. 
7.1.4. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 13: List of Data Displays and 
will be based on GSK data standards and statistical principles. 


 
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7.2. 
Secondary Efficacy Analyses 
7.2.1. 
Endpoint / Variables 
7.2.1.1. ORR based on Investigator Assessment 
ORR based on investigator-assessed response will be analysed as one of the secondary 
endpoints. 
ORR at primary analysis will be analyzed based on the confirmed responses, which will 
be derived based on the algorithm specified in Table 3.   
ORR at IA should also be analyzed based on confirmed responses if available. However, 
in case a participant has achieved a response of PR or better at data cut, which was not 
confirmed due to the time constraints (too short timeframe for the next assessment) but 
with a potential to be confirmed through subsequent assessments after interim, the 
participant will also be considered as a responder; if the participant dies or discontinues 
study or starts other anti-cancer therapy prior to confirming the response, the participant 
will not be considered as a responder at IA. 
7.2.1.2. Clinical Benefit Rate (CBR) 
CBR is defined as the percentage of participants with a confirmed minimal response 
(MR) or better, according to the IMWG Response Criteria [Kumar, 2016]. CBR will be 
summarized in the same way as ORR. No hypothesis testing will be performed for CBR.  
At primary analysis, CBR based on both IRC and investigator assessment will be 
summarized. At interim analysis, only CBR based on investigator assessment will be 
summarized. 
7.2.1.3. Duration of Response (DoR) 
DoR is defined as the time from first documented evidence of confirmed PR or better 
until the earliest date of confirmed disease progression (PD) per IMWG, or death due to 
PD among participants who achieve a response (i.e., confirmed PR or better). Responders 
without confirmed PD will be censored at the censoring time point for Time to 
Progression as specified in .Table 5 of Section 7.2.1.6.  
DoR will be analysed at the time of final ORR analysis, also at study close out if 
applicable, based on responses assessed by both IRC and investigator.  
7.2.1.4. Time to Response (TTR) 
TTR is defined as the time between the date of randomization and the first documented 
evidence of confirmed response (PR or better), among participants who achieve a 
response (i.e., confirmed PR or better).  
TTR will be analysed at the time of final ORR analysis, based on responses assessed by 
both IRC and investigator. 


 
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7.2.1.5. Progression Free Survival (PFS) 
PFS is defined as the time from randomization until the earliest date of confirmed PD per 
IMWG, or death due to any cause.    
PFS will be analysed at the time of final ORR analysis, also at study close out if 
applicable, based on responses assessed by both IRC and investigator. 
A summary of the assignments for progression and censoring dates for PFS are specified 
in Table 4 below. 
Table 4 
Assignments for Progression and Censoring Dates for PFS Analysis 
Situation 
Date of Event 
(Progression/Death) or 
Censoring  
Outcome Event 
(Progression/Death) Or 
Censored 
No (or inadequate) baseline 
tumor assessments [1] and the 
subject has not died (if the 
subject has died follow the 
rules for death indicated at the 
bottom of the table) 
Randomization  
Censored 
No post-baseline assessments 
and the subject has not died (if 
the subject has died follow the 
rules for death indicated at the 
bottom of the table) 
Randomization 
Censored 
Progression documented 
without extended loss-to-
follow-up time  
Date of assessment of 
progression [1] 
Event 
No progression (or death)  
Date of last ‘adequate’ 
assessment of response [2] 
Censored 
New anticancer treatment 
started (prior to documented 
disease progression or death) 
[3].  
Date of last ‘adequate’ 
assessment of response [2] (on 
or prior to starting anti-cancer 
therapy)  
Censored 
Death without extended loss-
to-follow-up time 
Date of death 
Event 
Death or progression after an 
extended loss-to-follow-up time 
(two or more missed cycles + 7 
day window) [4] 
Date of last ‘adequate’ 
assessment of response [2] 
prior to PD/death (prior to 
missed assessments) 
Censored 


 
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Situation 
Date of Event 
(Progression/Death) or 
Censoring  
Outcome Event 
(Progression/Death) Or 
Censored 
Death or progression after an 
extended loss-to-follow-up time 
from randomization 
Date of randomization 
Censored 
 
[1] Adequate baseline assessment is defined as at baseline, a patient has at least one of the following measurements: 
a. Serum M-protein ≥0.5 g/dL (≥5 g/L) or b. Urine M-protein ≥200 mg/24h or c. Serum FLC assay: Involved FLC 
level 10 mg/dL (100 mg/L) and an abnormal serum free light chain ratio (<0.26 or >1.65)  
[2] An adequate assessment is defined as an assessment where the IRC/Investigator determined response is sCR, 
CR, VGPR, PR, MR, or SD. 
[3] If PD or death and New anti-cancer therapy occur on the same day assume the progression or death was 
documented first (e.g., outcome is progression or death and the date is the date of the assessment of progression 
or death). If anti-cancer therapy is started prior to any adequate assessments, censoring date should be the date 
of randomization. 
[4] Refer to Section 15.5.4 “Extended Loss to Follow-up or Extended Time without an Adequate Assessment”. 
 
7.2.1.6. Time to Progression (TTP) 
TTP is defined as the time from randomization until the earliest date of confirmed PD per 
IMWG, or death due to PD. 
TTP will be analysed at the time of final ORR analysis, also at study close out if 
applicable, based on responses assessed by both IRC and investigator. 
A summary of the assignments for progression and censoring dates for TTP are specified 
in Table 5. 
Table 5 
Assignments for Progression and Censoring Dates for TTP Analysis 
Situation 
Date of Event 
(Progression/Death) or 
Censoring  
Outcome Event 
(progression/Death) Or 
Censored 
No (or inadequate) baseline 
tumor assessments [1] and the 
subject has not died (if the 
subject has died follow the 
rules for death indicated at the 
bottom of the table) 
Randomization  
Censored 
No post-baseline assessments 
and the subject has not died (if 
the subject has died follow the 
rules for death indicated at the 
bottom of the table) 
Randomization 
Censored 


 
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Situation 
Date of Event 
(Progression/Death) or 
Censoring  
Outcome Event 
(progression/Death) Or 
Censored 
Progression documented at or 
between scheduled visits 
Date of assessment of 
progression [1] 
Event 
No progression (or death)  
Date of last ‘adequate’ 
assessment of response [2] 
Censored 
New anticancer treatment 
started (prior to documented 
disease progression or death) 
[3]. 
Date of last ‘adequate’ 
assessment of response [2] (on 
or prior to starting anti-cancer 
therapy) 
Censored 
Death due to progression 
without extended loss-to-
follow-up time  
Date of death 
Event 
Death from causes other than 
progression without extended 
loss-to-follow-up time 
Date of death 
Censored 
Death or progression after an 
extended loss-to-follow-up time 
(two or more missed cycles + 7 
day window) [4] 
Date of last ‘adequate’ 
assessment of response [2] 
prior to PD/death (prior to 
missed assessments) 
Censored 
Death or progression after an 
extended loss-to-follow-up time 
from randomization 
Date of randomization 
Censored 
Adequate baseline assessment is defined as at baseline, a patient has at least one of the following 
measurements: a. Serum M-protein ≥0.5 g/dL (≥5 g/L) or b. Urine M-protein ≥200 mg/24h or c. 
Serum FLC assay: Involved FLC level ≥5 mg/dL (≥50 mg/L) and an abnormal serum free light 
chain ratio (<0.26 or >1.65). 
An adequate assessment is defined as an assessment where the IRC/Investigator determined 
response is sCR, CR, VGPR, PR, MR, or SD. 
If PD or death and New anti-cancer therapy occur on the same day assume the progression or 
death was documented first (e.g., outcome is progression or death and the date is the date of the 
assessment of progression or death). If anti-cancer therapy is started prior to any adequate 
assessments, censoring date should be the date of randomization. 
Refer to Section 15.5.4 “Extended Loss to Follow-up or Extended Time without an Adequate 
Assessment”. 


 
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7.2.1.7. Overall Survival (OS) 
OS is defined as the time from randomization until death due to any cause.  Participants 
who withdraw consent from the study or are lost to follow-up will be censored at the time 
of withdrawal or lost to follow-up. Participants who do not have a death record at the 
clinical cut-off date for the analysis will be censored at the last known alive date. The last 
contact date will be determined by the maximum collection/assessment date from among 
selected data domains within the clinical database.  
An OS analysis will be performed at the time of the primary ORR analysis.  An updated 
OS analysis will be performed at the end of study as defined in Section 4.6 of the 
protocol. 
7.2.2. 
Summary Measure 
• For ORR based on investigator-assessed responses, the number and percentage of 
participants with BOR in the following response categories will be summarized by 
dose level: 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 2-sided 97.5% exact 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. A list of investigator-assessed response at each visit will be 
listed. In addition, a summary table of IRC-assessed and investigator-assessed best response 
with confirmation will be provided to assess the concordance rate.  
 
• For CBR, the number and percentage of participants with the BOR in the following 
response categories will be summarized by dose level: sCR, CR, VGPR, PR, MR, 
clinical benefit response (sCR+CR+VGPR+PR+MR), SD, PD, and NE. The 
corresponding exact 95% CI for CBR will also be provided. Participants with 
unknown or missing responses will be treated as non-responders, i.e., these 
participants will be included in the denominator when calculating percentages of 
response. Analysis of CBR will be based on both IRC and investigator assessed 
responses assessed by both IRC and investigator. 
 
• DoR will be summarized using Kaplan-Meier method by dose level for participants 
with a confirmed PR or better. If there are a sufficient number of responders who 
subsequently progress or die due to PD, median DoR, first and third quartiles and 
95% CI, will be estimated using the Brookmeyer-Crowley method [Brookmeyer, 
1982]. A figure and listing of DoR time will also be provided. Analysis of DoR will 
be based on both IRC and investigator-assessed responses. A Kaplan Meier curve of 
Duration of Response by Dose Delay Category Based on Independent Reviewer - 
Assessed Response will be provided. A Kaplan Meier curve of Duration of Response 
by Response Category based on Independent Reviewer-Assessed Response will be 
provided. Hazard ratio estimated using the Pike estimator will be provided. 
 
• TTR will be summarized descriptively if there are sufficient number of responses by 
dose level, using median(s) and quartiles for participants with a confirmed response 
of PR or better. Analysis of TTR will be based on both IRC and investigator-assessed 


 
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responses. Summary of Time to Best Response based on Independent Reviewer - 
Assessed Response will also be provided. 
 
• PFS will be summarized using Kaplan-Meier method by dose level. If there is a 
sufficient number of progressions or deaths, median PFS, first and third quartiles, 6-
month PFS rate, and 95% CIs will be estimated using the Brookmeyer-Crowley 
method [Brookmeyer, 1982]. A figure and listing of PFS time will also be provided. 
Analysis of PFS will be based on both IRC and investigator-assessed responses. 
Summary and Kaplan Meier curve by Response Category Based on Independent 
Reviewer-Assessed Response will be provided. 
 
• TTP will be summarized using Kaplan-Meier method by dose level. If there is a 
sufficient number of progressions or death due to PD, median TTP, first and third 
quartiles and 95% CI, will be estimated using the Brookmeyer-Crowley method 
[Brookmeyer, 1982]. A figure and listing of TTP time will also be provided. Analysis 
of TTP will be based on both IRC and investigator-assessed responses. 
 
• OS will be summarized using the Kaplan-Meier method by dose level. For each dose 
level, the Kaplan-Meier estimates for the median overall survival time, the first and 
third quartiles will be presented, along with 95% CIs if there are a sufficient number 
of deaths. A graph of survival curves and a listing of survival times will also be 
provided. In addition, pending on maturity of data, the survival probability at 6, 12 
and 18 months with 95% CI will be estimated using Kaplan-Meier method. Summary 
and Kaplan Meier curve by Response Category Based on Independent Reviewer-
Assessed Response will be provided. 
7.2.3. 
Population of Interest  
For frozen liquid cohort, CBR, TTR, and DoR will be analyzed using both ITT and 
Efficacy population, and other TTE endpoints will be analyzed using ITT population 
only. 
 
For lyophilized cohort, all secondary efficacy endpoints will be analyzed using Lyo 
population. 
7.2.4. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 13: List of Data Displays and 
will be based on GSK data standards and statistical principles. 
Unless otherwise specified, endpoints / variables defined in Section 7.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate) and 
listed. 
 


 
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7.3. 
Exploratory Efficacy Analyses 
7.3.1. 
Endpoint / Variables 
7.3.1.1. Minimal Residual Disease (MRD) Negativity Rate 
MRD negativity rate is defined a: the percentage of participants who are MRD negative by Next 
Generation Sequencing (NGS).  
7.3.2. 
Summary Measure 
7.3.2.1. MRD Negativity Rate 
For MRD negativity rate based on bone marrow testing using Next Generation 
Sequencing (molecular negativity), the number and percentage of participants who have 
achieved MRD negativity will be summarized by dose level. The corresponding exact 
95% CI for MRD negativity rate will also be provided. If data permit, duration of MRD 
negativity will be analysed using Kaplan-Meier method in participants who have 
achieved MRD negativity. Information of MRD will be included in the listing of 
response. If data is available, imaging-based assessment of MRD (i.e. PET-CT) will also 
be included in the listing and related to NGS testing. 
7.3.3. 
Population of Interest  
The exploratory efficacy analyses will be based on the ITT population for frozen liquid 
cohort, and Lyo population for lyophilized cohort. 
7.3.4. 
Statistical Analyses / Methods 
Details of the planned displays will be provided in Appendix 13: List of Data Displays, 
based on GSK data standards, in the final version of the RAP. 


 
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8. 
SAFETY ANALYSES 
The safety analyses will be based on the “Safety” population for frozen liquid cohort, and 
‘Full Analysis’ population for frozen liquid cohort plus lyophilized cohort (side-by-side 
presentation). If needed, the safety analyses for lyophilized cohort alone will be based on 
the ‘Lyo’ population. 
Unless otherwise specified, no ‘Total’ column will be provided for safety outputs, and the 
sorting will be based on descending order of incidence in 3.4 mg/kg arm. In case the 2.5 
mg/kg becomes the selected dose post primary analysis, relevant outputs will be recreated 
with sorting based on descending order of incidence in 2.5 mg/kg arm 
8.1. 
Adverse Events Analyses 
Adverse events analyses including the analysis of adverse events (AEs), Serious AEs 
(SAEs) and other significant AEs will be based on GSK Core Data Standards.  
An overview summary of AEs, including counts and percentages of subjects with any 
AE, AEs related to study treatment, Grade 3&4 AEs, Grade 3&4 AEs related to study 
treatment, AEs leading to permanent discontinuation of study treatment, AE leading to 
dose reductions, AEs leading to dose delays, AEs related to study treatment and leading 
to permanent discontinuation of study treatment, SAEs, SAEs related to study treatment, 
fatal SAEs, and fatal SAEs related to 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). The summary will be 
displayed by SOC and PT. 
The relationship between MedDRA SOC, PT, and Verbatim Text will be displayed. 
Adverse events will be coded using the standard Medical Dictionary for Regulatory 
Affairs (MedDRA dictionary) and graded by the investigator according to the NCI-
CTCAE, (version 4.03).   
A summary of number and percentage of subjects with any adverse events by maximum 
grade will be produced. AEs will be sorted by Preferred term (PT) in descending order. 
The summary will use the following algorithms for counting the subject: 
• 
Preferred term row: Subjects experiencing the same AE preferred term several 
times with different grades will only be counted once with the maximum grade. 
• 
Any event row: Each subject with at least one adverse event will be counted only 
once at the maximum grade no matter how many events they have. 
The frequency and percentage of AEs (all grades) will be summarized and displayed in 
two ways: 1) in descending order by PT only and 2) in descending order by SOC and PT. 
In the SOC row, the number of subjects with multiple events under the same SOC will be 


 
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counted once. In addition, a summary of cumulative incidence of AE by number of doses 
received at first occurrence will be provided.   
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 in two ways: 1) by 
maximum grade sorted by PT in descending order and 2) in descending order by SOC 
and PT. 
In addition, AEs of maximum grade of 3 or higher will be summarized separately by PT. 
All AEs will be listed. Additionally, a listing of subject IDs for each individual AE will 
be produced.  
The details of the planned displays are provided in Appendix 13: List of Data Displays. 
8.2. 
Adverse Events of Special Interest Analyses 
Adverse events of special interest for GSK2857916 include eye disorder, 
thrombocytopenia, infusion related reactions, and neutropenia graded via CTCAE, and 
corneal event per GSK scale.  
8.2.1. 
Thrombocytopenia, infusion related reactions, and neutropenia 
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. For neutropenia, event will be 
identified using a comprehensive list of MedDRA terms based on clinical review. 
Changes to the MedDRA dictionary could 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 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 SRT agreements in place at the 
time of reporting.  
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 to 
onset and duration of first occurrence for each type of events will be summarized using 
summary statistics mean, standard deviation, median, minimum value, and maximum. 
The number and percentage of subjects who have time to onset of first occurrence (1-21, 
22-42, 43-63, >63 days) will be reported. The number and percentage of subjects who 
have duration of first occurrence (1-21, 22-42, >42 days) will be reported. 
The summary of event characteristics will also be provided, including number of subjects 
with any event, number of events, number of subjects with any event that is serious, 
number of subjects with any event that is related to study treatment, number of 
occurrences (One, Two, Three or more), maximum grade, outcomes and the action taken 
for the event. The percentage will be calculated in two ways, one with number of subjects 


 
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with event as the denominator and the other with total number of subjects as the 
denominator. 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. if a subject has an event leading to both study treatment 
discontinuation and dose reduction, the subject will be counted once under both actions. 
For each of these events, a summary of cumulative incidence by number of doses 
received at first occurrence will be provided.  
For thrombocytopenia, number and percentage of subjects with grade 3 or 4 platelet 
count decreased (based on lab data) and concomitant grade 2 or above bleeding event will 
be summarized. A bleeding event will be considered as concomitant only if the start date 
is within  3 days of the lab event. 
For neutropenia, number and percentage of subjects with grade 3 or 4 neutrophil count 
decreased (based on lab data) and concomitant infection event will be summarized. An 
infection event will be considered as concomitant only if the start date is within  7 days 
of the lab event. 
The details of the planned displays are provided in Appendix 13: List of Data Displays. 
8.2.2. 
Eye disorder (CTCAE) 
For AE in eye disorder SOC (CTCAE), an overview table and the listing will be 
provided.  
In addition, for each of selected five types of event within eye disorder SOC 
(keratopathy, dry eye, blurred vision, photophobia, and eye pain), the following summary 
tables will be provided if the incidence rate ≥ 10%:is observed in 3.4mg/kg frozen liquid 
cohort  
1. Event overview 
2. Summary table by PT and Maximum Grade 
3. Summary of event characteristics 
4. Summary of time to onset, duration, and outcome 
5. Summary of cumulative incidence by PT and number of doses received at first 
occurrence 
6. Summary of percentage of time on study treatment with ongoing event 
8.2.3. 
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 GSK2857916. 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 this GSK scale 
based on corneal findings and visual acuity Ophthalmic Exam (collected from Ocular 


 
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form) can be found in Appendix 9 Table 22 and Table 23 of study protocol (Version: 
GSK Document Number TMF-13990464 ). 
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 15.6.2 for 
definition) with corneal events (GSK scale) of grade ≥ 2 and grade ≥ 3 
respectively  
b. Summary of onset time and duration of the first occurrence of corneal 
event (GSK scale) of a) grade 2 or above; 2) grade 3 or above. 
3. Summary of actions taken with study treatment (e.g. dose 
reduction/delay/permanent discontinuation) 
4. Summary of time to re-initiation of study treatment post treatment delay due 
to corneal events (GSK scale) 
5. Change in grade of corneal events (GSK scale) from EOT to last follow-up 
6. Summary of worst post-baseline corneal events (GSK scale) 
7. Summary of worst post-baseline corneal events (GSK scale) by best response 
(PR or better vs. otherwise) 
8. Summary of resolution (improve to grade 1 or better) in corneal events (GSK 
scale) during Follow-up period (from EOT visit to last follow-up visit). 
9.  Logistic regression analysis will be performed to explore possible risk factors 
for developing corneal Events (GSK scale ≥ 2). In addition to dose arm (3.4 
mg/kg vs 2.5 mg/kg), Sex (Male vs Female), Age Group (< 65 vs. ≥ 65 years), 
Race (White, Other), the following risk factors will also be considered: 
a. History of intraocular surgery: (Yes vs. No) 
b. Lens status (pseudophakia vs natural lens) at baseline 
c. Known history of dry eye per screening questionnaire (Presence vs. 
Absence) 
d. Presence of keratopathy at baseline exam (None vs. Mild vs. 
Moderate/Severe) 
Covariates will be selected using stepwise variable selection with entry and 
exit criteria of alpha=0.05. 
10.  Summary of Blurred Vision and Dry Eye Events versus GSK Scale. 
11. Summary of Ocular Symptoms and Visual Acuity Change (GSK Scale) by 
Worst Grade of Keratopathy 
12. Summary of Ocular Symptoms and Visual Acuity Change (GSK Scale) by 
Worst Grade of Corneal Events (GSK Scale) 
13. Summary of Ocular Symptoms and Visual Acuity Change (>=2 lines in Better 
Eye) by Worst Grade of Corneal Exam Finding 
14. Summary of Eye Disorder Events (CTCAE) Leading to Dose Delays by 
Preferred Term and Maximum Grade. 
15. Summary of Subjects with Dose Delay due to Eye Disorder Events (CTCAE) 
at the Time of Data Cutoff 


 
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16. Summary of Vision Blurred, and Dry Eye by Preferred Term in Subjects with 
Keratopathy 
17. Summary of Vision Blurred, and Dry Eye by Preferred Term and Maximum 
Grade in Subjects with Keratopathy 
18. Summary of Ocular Symptoms (CTCAE) by Preferred Term and Maximum 
Grade in Subjects with Keratopathy 
19. Summary of Ocular Symptoms (CTCAE) by Preferred Term and Maximum 
Grade 
20. Summary of Blurred Vision and Dry Eye Events versus Keratopathy 
21. Summary of Ocular Symptoms (CTCAE) versus Keratopathy 
22. Summary of Duration of Keratopathy with Concurrent Blurred Vision or Dry 
Eye 
23. Summary of Duration of Keratopathy with Concurrent Ocular Symptoms 
(CTCAE) 
24. Summary of GSK scale Events Characteristics II 
25. Summary of Corneal Exam Finding (GSK scale) Characteristics II 
26. Summary of Visual Acuity Change (GSK scale) Characteristics II 
27. Summary of Maximum Grade for Corneal Exam Finding (GSK scale) 
28. Summary of Maximum Grade for Visual Change (GSK scale) 
29. Summary of Worsening in Best Corrected Visual Acuity (BCVA) Score 
(logMAR Score) Characteristics II 
30. Summary of Blurred Vision and Dry Eye Event Characteristics II in Subjects 
with Keratopathy 
31. Summary of Ocular Symptoms (CTCAE) Event Characteristics II in Subjects 
with Keratopathy 
32. Summary of Unilateral Worsening in Best Corrected Visual Acuity (BCVA) 
to 20/50 or Worse Characteristics II 
33. Summary of Bilateral Worsening in Best Corrected Visual Acuity (BCVA) to 
20/50 or Worse Characteristics II 
34. Summary of Unilateral Worsening in Best Corrected Visual Acuity (BCVA) 
to 20/200 or Worse Characteristics II 
35. Summary of Bilateral Worsening in Best Corrected Visual Acuity (BCVA) to 
20/200 or Worse Characteristics II 
36. Percentage of Subjects with Blurred Vision/Dry Eye Event Associated with 
Worsening in Best Corrected Visual Acuity (BCVA) to 20/50 or Worse 
37. Percentage of Subjects with Ocular Symptoms (CTCAE) Associated with 
Worsening in Best Corrected Visual Acuity (BCVA) to 20/50 or Worse 
38. Update of Resolution Status for Unresolved Corneal Exam Finding 
39. Update of Resolution Status for Unresolved Corneal Exam Finding Patients 
with Interview Clinical data 
40. Update of Resolution Status for Unresolved Worsening in Best Corrected 
Visual Acuity (BCVA) Score (logMAR Score) 
41. Update of Resolution Status for Unresolved Blurred Vision and Dry Eye 
Events in Subjects with Keratopathy 
42. Update of Resolution Status for Unresolved Ocular Symptoms (CTCAE) in 
Subjects with Keratopathy 
43. Summary of Worst Post-baseline Change in Best Corrected Visual Acuity 
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44. Summary of Worsening in Best Corrected Visual Acuity (BCVA) Score 
(logMAR Score >=0.12) Characteristics II 
45. Update of Resolution Status for Unresolved Worsening in Best Corrected 
Visual Acuity (BCVA) Score (logMAR Score >=0.12) 
46. Summary of Vision Blurred by Preferred term and Best Response Based on 
Independent Review Committee 
47. Summary of Dry Eye by Preferred term and Best Response Based on 
Independent Review Committee 
48. Summary of Vision Blurred by Maximum Grade, and Best Response Based 
on Independent Review Committee 
49. Summary of Dry Eye by Maximum Grade, and Best Response Based on 
Independent Review Committee 
50. Summary of Best Corrected Visual Acuity (BCVA) Score (Snellen Score) at 
Baseline Compared to 20/50 
51. Worsening in Best Corrected Visual Acuity (BCVA) Score (logMAR Score) 
Excluding Subjects with Follow-up Shorter Than 80 Days 
52. Summary of worst-case post baseline shift from baseline by BCVA categories 
53. Summary of Worst-case Post Baseline Change from Baseline in Best 
Corrected Visual Acuity (BCVA)Score (logMAR score) 
54. Summary of Worst-case Post Baseline Change from Baseline in Best 
Corrected Visual Acuity (BCVA)Score (logMAR score) in Subjects with 
Worsening to 20/50 or Worse in the Better Eye 
55. Summary of Worst-case Post Baseline Change from Baseline in Best 
Corrected Visual Acuity (BCVA)Score (logMAR score) in Subjects with 
Worsening to 20/50 or Worse in at Least One Eye but not the Better Eye 
56. Summary of Characteristics II for Keratopathy 
57. Summary of Dose Modifications for Subjects with Keratopathy 
58. Summary of Maximum Grade for Corneal Events (GSK scale) 
59. Summary of Time from Onset of Last Occurrence to Last Exam in Subjects 
Who Did Not Recover from Grade 2 or Higher Corneal Exam Finding (GSK 
Scale) When Follow Up Ended 
60. Summary of Ocular Symptoms by Preferred Term and Maximum Grade in 
Subjects with Worst Grade of Corneal Exam Findings (GSK scale) =1 
61. Summary of Duration of Exposure since Re-start after First Dose Delay Due 
to Eye Disorder Events (CTCAE) 
62. Summary of Corneal Events (GSK Scale) Occurrences After Dose Reduction 
to 1.92 mg/kg 
63. Summary of Characteristics II for the Event of Giving up Driving due to 
Eyesight 
64. Summary of Characteristics II for the Event of Giving up Reading due to 
Eyesight 
65. Listing of Resolution in Grade of Corneal Events (GSK Scale) for each 
Corneal Event in patients experiencing >1 event 
66. Listing of BCVA for patients who gave up driving due to eyesight 
67. Listing of BCVA for patients who experienced difficulty reading newspapers 
due to eyesight 
68. Bar Chart of Grade of Corneal Exam Finding by Cycle 


 
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69. Plot of Time to Recovery Post Treatment Discontinuation for Corneal Exam 
Findings 
70. Plot of Time to Recovery Post Treatment Discontinuation for Keratopathy 
71. Profile plot of patients with maximum corneal toxicity grade will be provided. 
72. Plot of Visual Acuity and Corneal Finding Grade for subjects experiencing >1 
Corneal Event (GSK Scale) for  2.5 mg/kg arm will be produced. 
 
Details of the planned displays are provided in Appendix 13: List of Data Display. 
8.3. 
Deaths and Serious Adverse Events 
All deaths will be summarised based on the number and percentage of subjects. This 
summary will classify subjects by time of death relative to the last dose of medication 
(>30 days or 30 days) and primary cause of death (disease under study, SAE possibly 
related to study treatment, or other). A supportive listing will be generated to provide 
subject-specific details on subjects who died.  
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 
provided.   
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 
subject-level details will be generated for 
• 
Fatal SAEs  
• 
Non-Fatal SAEs. 
8.4. 
Adverse Events Leading to Discontinuation and Dose 
Modification 
The following categories of AEs will be summarized separately by PT and separate 
supportive listings will be generated with subject level details for those subjects: 
• 
AEs Leading to Permanent Discontinuation of Study Treatment  
• 
AEs Leading to Dose Interruptions or Delays 
• 
AEs Leadings to Dose Reductions 
8.5. 
Ocular findings from ophthalmic exam  
As outlined in study protocol (Version: GSK Document Number TMF-13990464 ) 
Schedule of Activities (Table 1 of Section 1.2), ophthalmic exams are scheduled at 


 
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screening, during the study, and follow-up period for subjects in both general study and 
ocular sub-study. The ocular findings from ophthalmic exams will be analysed as 
described below. 
1. For general study from baseline to last follow-up, the following analysis will be 
performed:  
 
a. Best corrected visual acuity (BCVA): 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 will be summarized by eye (R/L) and subject (worse 
eye and better eye). Number (%) of subjects with a decline in BCVA to 
‘light perception’ (LP) or ‘no light perception’ (NLP) due to corneal 
finding anytime post-baseline will also be provided.  
b. Intraocular Pressure (IOP): summary table of 1) Number (%) of subjects 
with IOP ≥ 22mm Hg anytime post-baseline; 2) Number (%) of subjects 
who start treatment for IOP after 1st dose of study drug. 
c. Pupillary Exam: shift table (Normal to Abnormal) from baseline to worst 
post-baseline by subject (worse eye) 
d. Extraocular Muscle Movement: shift table (Full Intact: Yes to No) from 
baseline to worst post-baseline by eye (R/L) and subject (worse eye) 
e. External Exam: shift table (Ptosis: No to Yes) from baseline to worst post-
baseline by eye (R/L) and subject (worse eye) 
f. Lids/Lashes/Lacrimal System: shift table (Blepharitis/MGD: No to Yes) 
from baseline to worst post-baseline by eye (R/L) and subject (worse eye) 
g. Conjunctival Exam:  
i. shift table (Chemosis: Absent to Present; Bulbar Conjunctiva 
White and Quiet: Yes to No; Palpebral Conjunctiva within normal 
limits: Yes to No) from baseline to worst post-baseline by eye 
(R/L) and subject (worse eye) 
h. Sclera: shift table (Scleritis: No to Yes) from baseline to worst post-
baseline by eye (R/L) and subject (both eyes in same ocular exam) 
i. Corneal Exam:  
i. Corneal epithelium findings: 
1. Shift table from baseline to worst post-baseline by eye 
(R/L) and subject (worse eye) for Corneal epithelium 
(Normal to Abnormal), Corneal ulcer (No to Yes), 
Microcystic edema (No to Yes), Microcystic without 
edema (Yes/No), Subepithelial haze (No to Yes), Corneal 
neovascularization (No to Yes), Stroma (Normal to 
Abnormal), Active opacity (No to Yes),  and Active edema 
(No to Yes). 
2. For punctate keratopathy, summary table of worst grade 
and most frequent grade across ocular exams by eye (R/L) 
and subject (worse eye) 
ii. Corneal endothelium findings: 


 
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1. Shift table from baseline to worst post-baseline by eye 
(R/L) and subject (worse eye) for Corneal endothelium 
(Normal to Abnormal) 
2. Summary table by eye (R/L) and subject (either eye) for 
presence of Descemet's folds and Endothelial lesion at any 
post-baseline ocular exam. 
j. Pachymetry: Summary table of number (%) of ≥ 5% increase from 
baseline at worst post-baseline by eye (R/L) and subject (either eye) 
k. Schirmer's Test/ Tear Break-up Time:  
i. Summary table of change from baseline to worst post-baseline by 
eye (R/L). 
ii. Shift table from baseline to worst post-baseline by eye (R/L).The 
categories for Schirmer’s Test are ≤ 5 mm, > 5 and ≤ 10 mm, and 
> 10 mm; the categories for Tear Break-up Time are: ≤ 5 sec, > 5 
and ≤ 10 sec, and > 10 sec.  
l. Slit Lamp Exam:  
i. Shift table from baseline to worst post-baseline by eye (R/L) and 
subject (worse eye) for Anterior Chamber: Deep/Quite (Yes to 
No); Iris: Flat, round and reactive (Yes to No); and Lens: Clear 
(Yes to No). 
ii. Summary tables of presence of iris findings ('Transillumination 
defect', 'Nodules', or 'Neovascularization') at any post-baseline 
ocular exam. 
iii. Shift table from baseline to worst post-baseline by eye (R/L) and 
subject (worse eye) for Pseudophakia (No to Yes), Nuclear 
sclerosis (No to Yes), Cortical cataract (No to Yes), and Posterior 
subcapsular cataract (No to Yes)  
iv. Summary table of number of subjects (%) underwent surgery due 
to cataract post-baseline. 
 
m. FUNDUS Photograph: Shift table from baseline to worst post-baseline by 
eye (R/L) and subject (worse eye) for Vitreous normal in appearance (Yes 
to No), PVD (No to Yes), Vitreous cell (No to Yes), Vitreous haze (No to 
Yes), Optic nerve normal in appearance (Yes to No), and Retina normal in 
appearance (Yes to No).  
2. General study from EOT visit to last follow-up visit: To assess the change in 
corneal findings after discontinuation of study treatment, among eyes and subjects 
(worse eye) with exam finding at EOT visit worse than baseline, the following 
analyses will be performed. 
 
a. Summary of change (worsening, no change, improvement) from EOT to 
last follow-up visit based on categories defined below by eye (R/L) and 
subject (worse eye)  
b. Summary of number (%) of eyes and subjects (worse eye) that resolve 
(improve to baseline level or better based on categories defined below), 
and descriptive summary of time from EOT visit to resolution among eyes 
and subjects (worse eye) that resolved 
 


 
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The parameters included in above analyses are:  
1. BCVA change from baseline in log MAR scale (< 0.12, ≥ 0.12 to < 0.3, ≥ 
0.3)  
2. IOP (≥ 22mm Hg/<22mm Hg) 
3. Corneal epithelium (Normal/Abnormal), Punctate Keratopathy 
(None/Mild /Moderate/Severe), Corneal ulcer (No/Yes), Microcystic 
edema (No/Yes), Microcystic without edema (No/Yes), Subepithelial haze 
(No to Yes), Corneal neovascularization (No to Yes), Stroma 
(Normal/Abnormal); Active opacity (No/Yes); Active edema (No/Yes) 
4. Corneal endothelium (Normal/Abnormal), Descemet's folds (No/Yes; 
Peripheral/Central), Endothelial lesion (Peripheral/Central) 
5. Pachymetry (increase from baseline < 5%, and ≥ 5%), Tear break up time 
(≤ 5 mm, > 5 and ≤ 10 mm, and > 10 mm), Schirmer’s test (≤ 5 sec, > 5 
and ≤ 10 sec, and > 10 sec) 
 
3. Ocular sub-study (Cycle 1-4): To evaluate the effect of topical corticosteroids on 
corneal findings, pending on the availability of data, the following analyses will 
be performed in up to 30 participants who will receive monocular topical 
corticosteroids for the first 4 cycles: 
 
a. Summary of worst grade during Cycle 1-4 of corneal events (GSK scale) 
in eyes randomized to topical corticosteroids treatment and eyes not.  
b. BCVA at baseline, at worst during Cycle 1-4, and worst and most frequent 
category (definite worsen, possible worsen, and no change/improved) of 
change from baseline during Cycle 1-4 will be summarized in eyes 
randomized to topical corticosteroids treatment and eyes not. Eyes with a 
decline in BCVA to ‘light perception’ (LP) or ‘no light perception’ (NLP) 
due to corneal finding anytime post-baseline will also be summarized.  
c. Summary of onset time to first study treatment (BCMA)-related corneal 
finding (GSK scale) in eyes randomized to topical corticosteroids 
treatment and eyes not.  
d. Summary of onset time to initiation of topical corticosteroids treatment in 
eyes randomized to no such treatment. 
e. Shift in corneal findings (per ocular exam) from baseline to worst during 
Cycle 1- 4 in eyes randomized to topical corticosteroids treatment and eye 
not. Corneal findings include Corneal epithelium (Normal to Abnormal), 
Punctate Keratopathy (None/Mild to Moderate/Severe), Corneal ulcer (No 
to Yes), Microcystic edema (No to Yes), Microcystic without edema (Yes 
to No), Subepithelial haze (No to Yes), Corneal neovascularization (No to 
Yes), Stroma (Normal to Abnormal), Active opacity (No to Yes), and 
Active edema (No to Yes). 
 
The details of the planned displays are provided in Appendix 13: List of Data Displays. 


 
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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 subjects and subjects’ 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 13: List of Data 
Displays. 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 subject has a decrease to low and an increase to high during 
the same time interval, then the subject 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. 
For spot urine albumin/creatinine ratio (mg/g), a shift table from baseline to worst post-
baseline will be provided.  
A supporting listing of laboratory data for subjects with abnormalities of potential clinical 
concern will be provided. A separate listing of laboratory data with character values will 
also be provided.  
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 at each particular 
visit. 


 
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8.7.1. 
Analyses of Liver Function Tests 
Summaries of hepatobiliary laboratory events including possible Hy’s law cases will be 
provided in addition to what has been described above.  
A plot of maximum ALT vs. baseline ALT will be generated. Plots of maximum total 
bilirubin versus maximum ALT, maximum AST versus maximum LDH, maximum AST 
versus maximum Creatinine Kinase, and maximum LDH versus maximum Creatinine 
Kinase will be generated. 
A Summary of Liver Monitoring/Stopping Event Reporting will be provided. The 
medical conditions data for subjects with liver stopping events will be listed. The 
substance use data for subjects with liver stopping events will be listed. 
8.8. 
Other Safety Analyses 
The analyses of non-laboratory safety test results including ECGs and vital signs will be 
based on GSK Core Data Standards, unless otherwise specified. The details of the 
planned displays are presented in Appendix 13: List of Data Displays. 
Unless otherwise specified, the denominator in percentage calculation at each scheduled 
visit will be based on the number of subjects with non-missing value at each particular 
visit. 
8.8.1. 
Performance Status 
ECOG performance status will be summarized at baseline and each post-baseline 
scheduled visit. Summaries will use frequency and percentage of subjects at each planned 
assessment time. A summary of change from baseline by scheduled visits will be 
performed, as well as the worst case post-baseline and the best case post-baseline changes 
during the study (improved, no change, deteriorated). 
A supporting listing will also be provided.  
8.8.2. 
ECG 
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 CTCAE grade and ranges: Grade 0 (<450 msec), 
Grade 1 (450-480 msec), Grade 2 (481-500 msec), and Grade 3 (≥501 msec). Summaries 
of grade increase will be provided. These summaries will display the number and 
percentage of subjects with any grade increase, increase to grade 2 and increase to grade 
3 in the worst case post-baseline only.  
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. A summary of change in QTc value will 


 
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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. 
A listing of QTc values of potential clinical importance will be provided 
 
The summaries and listing of QTc will use the collected values based on Fridericia 
formula. 
A figure plotting the baseline QTc and the worst-case post-baseline values will be 
produced. The figure will have reference lines at 480 and 500 msec for both the ordinate 
and the abscissa axes. There will be diagonal reference lines at equality (i.e. a 45 degree 
line), at equality plus 30 msec, and at equality plus 60 msec. 
8.8.3. 
LVEF 
Absolute change from baseline in LVEF will be summarized in the worst case post-
baseline only. Only the post-baseline assessments that used the same method (e.g. 
ECHO) as the baseline assessments will be used to derive the change from baseline. The 
change from baseline will be categorized as follows: 
• 
No change or any increase 
• 
Any decrease 
• 
>0-<10 decrease 
• 
10-19 decrease 
• 
>=20 decrease 
• 
>=10 decrease and >= LLN 
• 
>=10 decrease and < LLN 
• 
>=20 decrease and >= LLN 
• 
>=20 decrease and < LLN 
8.8.4. 
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. 


 
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9. 
PHARMACOKINETIC ANALYSES 
The pharmacokinetic analyses will be based on the “Full Pharmacokinetic” population. 
Concentration-time data collected in Cycles 1 and 3 under protocol amendment 2 were 
analysed using standard non-compartmental (NCA) methods at the time of primary 
analyses. Some parameters were determined for all participants and cycles.  The 
concentration-time data may be combined with data from other studies and will be 
analysed in a population approach using nonlinear mixed effects modelling. Full details 
are presented in Appendix 13: List of Data Displays. 
9.1. 
Drug Concentration Measures 
Refer to Appendix 5: Data Display Standards & Handling Conventions (Section 15.5.3 
Reporting Standards for Pharmacokinetic Parameters 
9.1.1. 
Non-compartmental Analysis 
• 
Pharmacokinetic parameters described in Table 6 below, were determined separately 
for each analyte, as data permitted. 
• 
The pharmacokinetic parameters in Cycles 1 and 3 under protocol amendment 2 or 
later were calculated by standard non-compartmental analysis according to current 
working practices and using Phoenix WinNonlin, version 6.3 or later, as data 
permitted. 
• 
The pharmacokinetic parameters C-EOI and Ctrough were determined directly from 
the concentration-time dataset for the other cycles under protocol amendment 2 and 
for participants enrolled prior to protocol amendment 2, as data permitted.  Note:  
For the dosing occasions with only predose and end of infusion samples, the end of 
infusion concentration (C-EOI) was not identified as Cmax. 
• 
All calculations of non-compartmental parameters were based on actual sampling 
times. 
Table 6 
Derived Pharmacokinetic Parameters 
Parameter 
Parameter Description 
AUC(0-t) 
Area under the concentration-time curve from time zero to the time of the last quantifiable 
concentration (C(t)) will be calculated using the linear trapezoidal rule for each incremental 
trapezoid and the log trapezoidal rule for each decremental trapezoid 
AUC(0-t’) 
Area under the concentration-time curve to a fixed time t’ 
AUC(0-) 
Area under the concentration-time curve during the dosing interval 
AUC(0-∞) 
Area under the concentration-time curve extrapolated to infinity will be calculated as:  
AUC = AUC(0-t) + C(t) / lambda_z  
%AUCex 
The percentage of AUC (0-∞) obtained by extrapolation (%AUCex) will be calculated as: 
[AUC(0-inf) – AUC(0-t)] / AUC(0-inf) x 100 
Cmax 
Maximum observed concentration, determined directly from the concentration-time data for 
each cycle.  Cmax will not be derived when only predose and EOI samples were collected. 
tmax 
Time to reach Cmax, determined directly from the concentration-time data for each cycle 
C, 
Trough concentration prior to the next dose for each cycle 


 
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Parameter 
Parameter Description 
Ctrough 
C-EOI 
Observed plasma concentration at the end of infusion 
t½ 
Apparent terminal half-life will be calculated as:  
t½ = ln(2) / lambda_z  
tlast 
Time of last observed quantifiable concentration  
CL 
Clearance  
Vss 
Volume of distribution at steady state  
z, 
lambda_z 
Terminal phase rate constant  
 
9.2. 
Population of Interest  
The pharmacokinetic (PK) analyses will be based on the ‘Full Pharmacokinetic’ 
population as defined in Section 4, unless otherwise specified. 
9.3. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 13: List of Data Display, based 
on GSK data standards and statistical principles. Unless otherwise specified, endpoints / 
variables defined in Section 9.1.1 will be summarised using descriptive statistics, 
graphically presented (where appropriate) and listed. 
9.3.1. 
Statistical Methodology Specification 
The following pharmacokinetic statistical analyses were performed when sufficient data 
were available. 
9.3.1.1. Assessment of Accumulation Ratio 
To assess the extent of accumulation following GSK2857916 repeat dosing, the observed 
accumulation ratio (Ro) for GSK2857916, total antibody, and cys-mcMMAF were 
determined as ratio of AUC and Cmax at Cycle 3 to AUC and Cmax at Cycle 1, 
respectively, using the data collected under protocol amendment 2.  The same AUC 
parameter [AUC(0-t’) or AUC(0-)] were used on the two occasions for each analyte, but 
analytes may have used different AUC parameters depending upon the data.  
Participants must have received the same dose without delay or change for Cycles 1, 2, 
and 3 to be included in this analysis (i.e., with dosing delays of 3 days). 
Ro(AUC) = AUC C3 / AUC C1; 
AUC is AUC(0-) or AUC(0-t’)  
Ro(Cmax) = Cmax C3 / Cmax C1 
Accumulation ratios of AUC and Cmax were summarised using descriptive statistics by 
planned initial dose level, graphically presented (where appropriate) and listed.  
An exploratory analysis was not performed considering the effect of dose delay or change 
on the ratio.  


 
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10. 
POPULATION PHARMACOKINETIC (POPPK) 
ANALYSES 
Plasma GSK2857916 concentration-time data may be combined with data from other 
studies and will be analysed using a population pharmacokinetic approach.  Details of the 
population PK analyses will be reported under a separate RAP, and the results of this 
analysis will be provided in a separate report. 


 
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11. 
PHARMACODYNAMIC AND BIOMARKER ANALYSES 
If data permit, the relationship between clinical response and other biologic characteristics 
including BCMA expression on tumour cells and sBCMA concentrations may be explored.  
Details of these analyses will be specified within a separate biomarker RAP, and the 
results of these analysis will be provided in a separate report. 
 


 
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12. 
PHARMACOKINETIC / PHARMACODYNAMIC 
ANALYSES 
12.1. 
Exposure-Response for Efficacy and Safety Endpoints 
If deemed appropriate and if data permit, exposure-response relationships between 
GSK2857916 exposure (e.g., dose, dose intensity, concentration, Cmax, or AUC) and 
clinical activity and/or toxicity (e.g., response, corneal event, AESIs) may be explored 
using population methods. If data permit, the effects of covariates may be explored.  
Details of these analyses will be reported under a separate RAP, and the results of this 
analysis will be provided in a separate report. 
 
12.2. 
Concentration-QTc Analyses 
Concentration-QTc Analyses were performed at the time of the primary analyses. For 
each ECG assessment, the individual subject’s QTcF change from baseline were 
calculated and were merged with time-matched PK concentration values for the 
timepoints at which they are available. QTcF change from baseline (y-axis) were plotted 
against the PK concentration data (x-axis) separately for each analyte (ADC, total mAb, 
and cys-mc-MMAF).  Linear regression analyses were performed for each analyte-
QTcF plot.  


 
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13. 
HEALTH OUTCOMES ANALYSIS 
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 analysis population for EORTC QLQ-C30 and EORTC QLQ-MY20 will follow the 
rule for efficacy analysis, while the analysis population for PRO-CTCAE, NEI-VFQ-25, 
and OSDI will follow the rule for safety analysis. 
13.1. 
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].  Details of deriving domain scores (9 scales and 6 single 
items) and summary score can be found in Section 15.11.1.  
For summary score and each of domain scores, the following outputs will be provided: 
• The descriptive summary of the actual value and change from baseline by visit. 
• The number (%) of patients with improvement in score ≥ 10, and ≥ 5 points 
respectively by visit. 
 
13.2. 
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 15.11.2.  
 
For each of four domain scores, the following outputs will be provided: 


 
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• 
The descriptive summary of the actual value and change from baseline by visit  
 
• 
Summary of the number (%) of patients with  improvement in score ≥ 10, and ≥ 5 
points respectively by visit. 
 
13.3. 
Patient-Reported Outcome Version of the Common Term 
Criteria for Adverse Events (PRO-CTCAE) 
The Patient-Reported Outcomes Version of the Common Terminology Criteria for 
Adverse Events (PRO-CTCAE) is a patient-reported outcome measure developed to 
evaluate symptomatic toxicity in patients on cancer clinical trials [Basch, 2014].  The 
PRO-CTCAE was designed to be used as a companion to the Common Terminology 
Criteria for Adverse Events (CTCAE), the standard lexicon for adverse event reporting in 
cancer trials.  The PRO-CTCAE includes an item library of 124 items representing 78 
symptomatic toxicities drawn from the CTCAE.  PRO-CTCAE provides a systematic yet 
flexible tool for descriptive reporting of symptomatic treatment side effects in cancer 
clinical trials.  The levels and related code values for PRO-CTCAE are shown below. 
 
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 each item 
attribute (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.  
13.4. 
National Eye Institute Visual 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 NEIVFQ-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 corneal 


 
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pain. Details of deriving domain scores and overall composite score can be found in 
Section 15.11.3.  
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. 
In addition, summary of worst change from baseline in overall composite score by worst 
grade of corneal event per GSK scale (0 vs 1-2, vs 3-4) will also be provided. The 
summary will be based on pooled data of frozen liquid cohort (2.5 and 3.4 mg/kg) and 
Lyo cohort (3.4 mg/kg).  
13.5. 
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]. 
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).  
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 by time will be provided. 
In addition, summary of worst change from baseline in total score by worst grade of 
corneal event per GSK scale (0 vs 1-2, vs 3-4) will also be provided. The summary will 
be based on pooled data of frozen liquid cohort (2.5 and 3.4 mg/kg) and Lyo cohort (3.4 
mg/kg).  
 


 
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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. 
Dmitrienko A, Wang MD. Bayesian predictive approach to interim monitoring in clinical 
trials. Statistics in Medicine. 2006 July 15;25(13):2178-2195. 
Fayers et. al., The EORTC QLQ-C30 Scoring Manual (3rd Edition) 2001 
GlaxoSmithKline Document Number TMF-13990464 Study ID205678.DREAMM-2: A 
Phase II, Open Label, Randomized, Two-Arm Study to Investigate the Efficacy and 
Safety of Two Doses of the Antibody Drug Conjugate GSK2857916 in Participants with 
Multiple Myeloma Who Had 3 or More Prior Lines of Treatment, Are Refractory to a 
Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed an Anti-CD38 
Antibody (DREAMM 2). Document Date 19-Nov-2021. 
Hwang IK, Shih WJ, De Cani JS. Group sequential designs using a family of type I error 
probability spending functions. Stat Med. 1990;9(12):1439-45. 
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. 
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. 


 
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Rajkumar SV. Updated Diagnostic Criteria and Staging System for Multiple Myeloma. 
Am Soc Clin Oncol Educ Book. 2016;35:e418-23. 
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: Protocol Deviation Management and Definitions 
for Per Protocol Population 
15.1.1. 
Exclusions from Per Protocol Population 
No per protocol population was defined for the study. 


 
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15.2. 
Appendix 2: Schedule of Activities 
15.2.1. 
Protocol Defined Schedule of Events 
Refers to Section 1.2 of Protocol (Version: GSK Document Number TMF-13990464 ). 


 
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15.3. 
Appendix 3: Assessment Windows 
15.3.1. 
Definitions of Assessment Windows for Analyses 
Not applied to the study. 
 


 
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15.4. 
Appendix 4: Study Phases and Treatment Emergent 
Adverse Events 
15.4.1. 
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/time ≤ Study Treatment Start Date/time 
On-Treatment 
Study Treatment Start Date/time < Date/time  
 
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 references time flag 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 
start date falls into the on-treatment period or if subject is ongoing (not all study 
treatment discontinuation records completed) or (end date is missing and start 
relative to treatment not 'AFTER'). Else assign to 'AFTER' if start date is after the 
on-treatment period or (end date is missing and start relative to treatment='AFTER').  
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.  
Concomitant medication starts relative to treatment and end relative to treatment flags are 
used to select data to include in the Concomitant Medication summaries as follows: 


 
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• 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'). 


 
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15.4.2. 
Treatment Emergent Flag for Adverse Events 
Flag 
Definition 
Treatment 
Emergent 
• 
Study Treatment Start Date ≤ AE Start Date  
• 
AE Start Date is missing 
NOTES:  
• 
If the study treatment stop date is missing, then the AE will be considered to be On-Treatment. 
• 
Time of study treatment dosing and start/stop time of AEs should be considered, if collected. 
 


 
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15.5. 
Appendix 5: Data Display Standards & Handling 
Conventions 
15.5.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software will be used. 
Reporting Area 
HARP Server 
: US1SALX00259 
HARP Compound 
: arprod\gsk2859716\MID205678\ 
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. 
15.5.2. 
Reporting Standards 
General 
• 
The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx): 
• 
4.03 to 4.23: General Principles 
• 
5.01 to 5.08: Principles Related to Data Listings 
• 
6.01 to 6.11: Principles Related to Summary Tables 
• 
7.01 to 7.13: Principles Related to Graphics  
• 
Do not include subject level listings in the main body of the GSK Clinical Study Report. All subject level 
listings should be located in the modular appendices as ICH or non-ICH listings 
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. 
• 
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 readings will be presented within the subject’s listings.  
Unscheduled Visits 
• 
Unscheduled visits will not be included in summary tables and/or figures. 
• 
For by planned time analysis, unscheduled visits will not be included; 
• 
For worst-case analysis, unscheduled visits will be included. 


 
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• 
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. 
15.5.3. 
Reporting Standards for Pharmacokinetic 
Pharmacokinetic Concentration Data 
PC Windows Non-
Linear (WNL) File 
PC WNL file (CSV format) for the non-compartmental analysis by Clinical 
Pharmacology Modelling and Simulation function will be created according to SOP 
00000314000: Non-Compartmental 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 
See separate population PK/exposure-response analysis RAP 
NONMEM/PK/PD 
File 
See separate population PK/exposure-response analysis RAP 
Pharmacokinetic Parameter Derivation 
PK Parameter to be 
Derived by 
Programmer 
The following PK parameters will be derived by the Programmer:  
• 
C-EOI and Ctrough for cycles with predose and EOI sampling only 
• 
Accumulation ratios based on Cycle 1 and Cycle 3 AUC and Cmax values 
Pharmacokinetic Parameter Data 
Is NQ impacted PK 
Parameters Rule 
Being Followed 
Yes, refer to [Standards for Handling NQ Impacted PK Parameters]. 
Descriptive Summary 
Statistics, Graphical 
Displays and Listings 
Refer to IDSL PK Display Standards.  
 
15.5.4. 
Extended Loss to Follow-up or Extended Time without an 
Adequate Assessment 
For subjects, if two or more scheduled disease assessments are missed and are then 
followed by an assessment of PD or death, PFS 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 49 days (6 weeks + 7 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 49 days, then 
PFS will be censored at the last adequate assessment prior to PD/death. 


 
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15.6. 
Appendix 6: Derived and Transformed Data 
15.6.1. 
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. This will also be applicable to relevant Potential Clinical Importance summary 
tables. 
Study Day 
• 
Calculated as the number of days from First Dose Date: 
• 
Ref Date = Missing              → Study Day = Missing  
• 
Ref Date < First Dose Date → Study Day = Ref Date – First Dose Date 
• 
Ref Data ≥ First Dose Date → Study Day = Ref Date – (First Dose Date) + 1     
 
15.6.2. 
Study Population 
Extent of Exposure 
• 
Number of days of exposure to study drug will be calculated based on the formula:   
Duration of Exposure in Days = min(Last infusionDate+20, Death date) – First infusion Date + 1 
• 
Participants who were randomized but did not report a treatment start date will be categorised as 
having zero days of exposure.  
• 
The cumulative dose will be based on the formula: 
Cumulative Dose (mg/kg) = Sum of Dose at Each Cycle 
• 
Dose intensity will be calculated based on the formula: 
• 
Dose intensity (mg/kg/3 week)  = Cumulative Dose/((last infusion date – first infusion date + 
21)/21) 
15.6.3. 
Efficacy 
Laboratory Parameters 
Serum M-protein, Urine M-protein, Serum FLC 
• 
If a laboratory value which is expected to have a numeric value for summary purposes, has a non-
detectable level reported in the database, where the numeric value is missing, but typically a character 
value starting with ‘<x’ or ‘>x’ (or indicated as less than x or greater than x in the comment field) is 
present, the number of significant digits in the observed values will be used to determine how much to 
add or subtract in order to impute the corresponding numeric value.  
o Example 1: 2 Significant Digits = ‘< x ‘becomes x – 0.01 
o Example 2: 1 Significant Digit = ‘> x’ becomes x + 0.1 
• 
Example 3: 0 Significant Digits = ‘< x’ becomes x – 1      
 


 
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15.6.4. 
Safety 
Adverse Events 
AE’S of Special Interest 
• 
Eye disorder (CTCAE) 
• 
Thrombocytopenia 
• 
Infusion-Related Reactions  
• 
Neutropenia 
• 
Corneal events (GSK scale): collected in Ocular form 
 


 
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15.7. 
Appendix 7: Reporting Standards for Missing Data 
15.7.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• 
Subject study completion (i.e. as specified in the protocol) was defined as ”A participant 
will be considered to have completed the study if he or she has received at least one 
dose of the study treatment and, has died or is still in follow-up when the study is 
closed, and has not withdrawn consent from study participation.”.  
• 
Withdrawn subjects will not 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.  
• 
Withdrawal visits will be slotted as per Appendix 3: Assessment Windows or will be 
summarised as withdrawal visits. 
15.7.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• 
Missing data occurs when any requested data is not provided, leading to blank fields on 
the collection instrument: 
o These data will be indicated by the use of a “blank” in subject 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. 
Responder 
Analysis  
• 
For endpoints which determine the percentage of responders, subjects with 
unknown/not evaluable or missing best overall response will be assumed to be non-
responders and will be included in the denominator when calculating the percentages. 
Time to 
Event  
• 
Because study treatment is dependent on the study endpoints (e.g., progression, i.e. 
not a fixed treatment duration), the length of treatment for each subject will depend on 
the efficacy and toxicity of the treatment, so the duration of treatment will vary across 
subjects. Similarly, the duration of follow up will also vary. All available time-to-event 
data will be analysed using suitable statistical methods; subjects with shorter treatment 
and follow-up due to the natural history of their disease or medical necessities of the 
treatment of their disease will not be considered to have missing time-to-event data. 
15.7.2.1. Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in subject listing displays. 
• 
Imputed partial dates will not be used to derive study day, duration (e.g. duration of 
adverse events), or elapsed time variables. In addition, imputed dates are not used for 
deriving the last contact date in the overall survival analysis dataset.  
• 
Imputed dates will not be displayed in listings. However, where necessary, display 
macros may impute dates as temporary variables for the purpose of sorting data in 
listings only. In addition, partial dates may be imputed for ‘slotting’ data to study time 
periods or for specific analysis purposes as outlined below.  


 
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Element 
Reporting Detail 
Adverse 
Events 
• 
The eCRF allows for the possibility of partial dates (i.e., only month and year) to be 
recorded for AE start and end dates; that is, the day of the month may be missing. 
o Missing Start Day: First of the month will be used unless this is before the start 
date of study treatment; in this case the study treatment start date will be used and 
hence the event is considered On-treatment as per Appendix 4: Study Phases and 
Treatment Emergent Adverse Events. 
o Missing Stop Day: Last day of the month will be used. 
• 
Completely missing start dates will remain missing, with no imputation applied. 
Consequently, time to onset and duration of such events will be missing. 
• 
Completely or partially missing end dates will remain missing, with no imputation 
applied. Consequently, duration of such events will be missing. 
Concomitant 
Medications/
Medical 
History 
• 
Partial dates for any concomitant medications recorded in the CRF will be imputed 
using the following convention: 
o If the partial date is a start date, a '01' will be used for the day and 'Jan' will be 
used for the month 
o If the partial date is a stop date, a '28/29/30/31' will be used for the day (dependent 
on the month and year) and 'Dec' will be used for the month. 
• 
The recorded partial date will be displayed in listings. 
New Anti-
Cancer 
Therapy/ 
Radiotherap
y/ 
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 temporarily imputed in order to define 
event and censoring rules for progression-free survival, response rate, time to 
progression, duration of response or time to response (i.e. start date for new anti-
cancer therapy). The imputed dates will not be stored on the anti-cancer therapy, 
radiotherapy, or surgical procedure datasets. 
• 
If missing start day, month, and year, then no imputation for completely missing dates 
• 
If missing start day and month, then no imputation should be done 
• 
If missing start day, then do the following: 
• 
If partial date falls in the same month as the last dose of study treatment, then assign to 
earlier of (date of last dose of study treatment+1, last day of month).  
• 
If partial date falls in the same month as the subject’s last assessment and the subject’s 
last assessment is PD, then assign to earlier of (date of PD+1, last day of month).  
• 
If both rules above apply, then assign to latest of the 2 dates  
• 
Otherwise, impute missing day to the first of the month. 
If missing end date, then no imputation should be done. 
Covariates 
for efficacy 
analysis 
(Date of 
initial 
diagnosis/ 
Last 
recurrence/ 
Last 
progression)  
• 
If both month and day are missing, first of January will be used 
If only day is missing, first of the month will be used 
Treatment 
end date 
• If there is more than one study treatment, imputation of missing treatment end date will 
be applied to all applicable treatments following rules below and treatment end date is 
the latest treatment end date across all study treatments. In general, completely missing 


 
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Element 
Reporting Detail 
end dates are not imputed, with the following exceptions for imputation of missing 
treatment end date at interim analyses. 
• For imputation of missing exposure end date at an interim analysis when subjects are 
still on treatment, the following conventions will be applied: 
o If the missing end date is in the last exposure record, the earliest of: the date of the 
data cut-off, the date of withdrawal from the study, or the death date will be used  
o If the missing end date is not in the last exposure record, treatment start date for 
the record will be used 
• The imputed treatment end date will be used to calculate cumulative dose and duration 
of treatment as specified in Section 15.6.2  
If treatment end date is missing for a cycle, treatment start date for the cycle will be used. 
PACT 
• For PACT subjects, subject’s last Visit date will be used as subject’s end of study date, 
wherever required. 
 


 
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15.8. 
Appendix 8: Values of Potential Clinical Importance 
15.8.1. 
Laboratory Values 
Reference ranges for all laboratory parameters collected throughout the study are 
provided by the laboratory. A laboratory value that is outside the reference range is 
considered either high abnormal (value above the upper limit of the reference range) or 
low abnormal (value below the lower limit of the reference range). Note: a high abnormal 
or low abnormal laboratory value is not necessarily of clinical concern. The laboratory 
reference ranges will be provided on the listings of laboratory data. Clinical laboratory 
test results outside of the reference range will be flagged in the listings. 
To identify laboratory values of potential clinical importance, National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03) will be used to 
assign grades to the relevant laboratory parameters. NCI-CTCAE v4.03 can be found at 
http://ctep.cancer.gov/reporting/ctc.html.  
For laboratory data which are not listed in the NCI CTCAE v4.03, a summary of values 
outside the normal range will be provided. 
15.8.2. 
ECG Parameters and vital signs 
For ECG and vital signs, outputs per the most updated IDSL standard up to the RAP 
effective date will be provided. 
Unless otherwise specified, ECG displays will be based on central reading. 


 
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15.9. 
Appendix 9: Population Pharmacokinetic (PopPK) Analyses 
15.9.1. 
Population Pharmacokinetic (PopPK) Dataset Specification 
See separate population PK/exposure-response analysis RAP  
15.9.2. 
Population Pharmacokinetic (PopPK) Methodology 
See separate population PK/exposure-response analysis RAP  


 
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15.10. 
Appendix 10: Pharmacokinetic / Pharmacodynamic 
Analyses 
15.10.1. 
Pharmacokinetic / Pharmacodynamic Dataset Specification 
See separate population PK/exposure-response analysis RAP  
15.10.2. 
Pharmacokinetic / Pharmacodynamic Methodology 
See separate population PK/exposure-response analysis RAP  


 
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15.11. 
Appendix 11: Health outcome Analyses 
15.11.1. 
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. 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third 
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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 et. al., The EORTC 
QLQ-C30 Scoring Manual (3rd Edition) 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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respectively), the mean change in EORTC QLQ-C30 score between baseline and follow-
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). 
15.11.2. 
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). 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third 
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Missing items can be handled similarly to EORTC QLQ-C30 as described in Section 
15.11.1.  
15.11.3. 
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 recorded values, and items of which 
recorded 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.  
 
 
CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third 
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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are 
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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by 
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15.12. 
Appendix 12: Abbreviations & Trade Marks 
15.12.1. 
Abbreviations 
Abbreviation 
Description 
A&R 
Analysis and Reporting  
ADA 
Anti-Drug Antibodies 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
Ae(0-t) 
Amount of drug excreted in urine from dosing to time t 
AUC 
Area under the concentration-time curve 
BCVA 
Best Corrected Visual Acuity 
BOR 
Best Overall Response 
CBR 
Clinical benefit rate 
CDISC 
Clinical Data Interchange Standards Consortium 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CI 
Confidence interval 
CK-MB 
Creatine kinase MB-isoenzyme 
CL 
Clearance 
Cmax 
Maximum observed plasma drug concentration 
CPMS 
Clinical Pharmacology Modelling & Simulation 
CPMS 
Clinical Pharmacology Modeling and Simulation 
CR 
Complete response 
CR 
Complete response 
CRM 
Continual Reassessment Method 
CS 
Clinical Statistics 
CSR 
Clinical Study Report 
CTR 
Clinical Trial Register 
Ctrough 
Concentration observed prior to the next dose 
CVb / CVw 
Coefficient of Variation (Between) / Coefficient of Variation (Within) 
Cys-mcMMAF 
Cysteine-maleimidocaproyl monomethyl auristatin F  
DBF 
Database Freeze 
DBR 
Database Release 
DLT 
Dose limiting toxicity 
DOB 
Date of Birth 
DOR 
Duration of response 
DP 
Decimal Places 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic Case Record Form 
eDiary 
Electronic Diary 
EMA 
European Medicines Agency 
EOI 
End of infusion 
EORTC 
European Organization for Research and Treatment of Cancer 
EOT 
Endo of treatment 
FACTS 
Fixed and adapted clinical trials simulator 


 
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Abbreviation 
Description 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Clinical Results Disclosure 
Requirements 
Fe(0-t) 
Fraction of administered dose excreted in urine from dosing to time t 
FLC 
Free light chain 
FTIH 
First time in human 
GSK 
GlaxoSmithKline 
IA 
Interim Analysis 
ICH 
International Conference on Harmonization 
IDMC 
Independent Data Monitoring Committee  
IDSL 
Integrated Data Standards Library 
IMMS 
International Modules Management System 
IMWG 
International Myeloma Working Group 
IOP 
Intraocular Pressure 
IP 
Investigational Product 
ITT 
Intent-To-Treat 
LDH 
Lactate dehydrogenase 
MM 
Multiple Myeloma 
MMAF 
Monomethyl auristatin F 
MMRM 
Mixed Model Repeated Measures 
MR 
Minimal response 
MRD 
Minimal Residual Disease 
MTD 
Maximum Tolerated Dose 
NCI-CTCAE 
National Cancer Institute – Common Terminology Criteria for Adverse 
Events 
N-CRM 
A modification of the Continual Reassessment Method (CRM) 
proposed by Neuenschwander et al. 
NEI-VFQ-25 
National Eye Institute Visual Functioning Questionnaire - 25 
NONMEM 
Nonlinear mixed effects modelling 
ORR 
Overall response rate 
OS 
Overall survival 
OSDI 
Ocular Surface Disease Index 
PACT 
Post Analysis Continued Treatment 
PCI 
Potential Clinical Importance  
PD 
Pharmacodynamics 
PD 
Progressive disease 
PDMP 
60 Plan 
PET 
Probability of early termination 
PFS 
Progression-free survival 
PK 
Pharmacokinetics 
PopPK 
Population PK 
PP 
Per Protocol 
PR 
Partial response 
PRO-CTCAE 
Patient-Reported Outcome Version of the Common Term Criteria for 
Adverse Events 


 
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Abbreviation 
Description 
QC 
Quality Control 
QLQ-C30 
Quality of Life Questionnaire 30-item Core module 
QLQ-MY20 
Quality of Life Questionnaire 20-item Multiple Myeloma module 
QoL 
Quality of life 
QTcB 
Bazett’s QT Interval Corrected for Heart Rate 
QTcF 
Fridericia’s QT Interval Corrected for Heart Rate 
RAMOS 
Randomization & Medication Ordering System  
RAP 
Reporting & Analysis Plan 
REML 
Restricted maximum likelihood 
Ro 
Observed accumulation ratio 
RP2 
Recommended Phase 2  
RRMM 
Relapsed / refractory multiple myeloma 
SAC 
Statistical Analysis Complete 
SAE 
Serious adverse event 
sBCMA 
Soluble B-cell maturation antigen 
sCR 
Stringent complete response 
SD 
Stable disease 
SDSP 
Study Data Standardization Plan 
SDTM 
Study Data Tabulation Model 
SOI 
Start of infusion 
SOP 
Standard Operation Procedure 
SPEP 
Serum protein electrophoresis 
SRT 
Safety Review Team 
t½  
Terminal phase half-life 
TA 
Therapeutic Area 
TFL 
Tables, Figures & Listings  
tlast 
Time of last quantifiable concentration 
tmax 
Time to maximum drug concentration 
TTBR 
Time to best response 
TTP 
Time to progression 
TTR 
Time to response 
ULN 
Upper limit of normal 
UPEP 
Urine protein electrophoresis 
VGPR 
Very good partial response 
Vss 
Volume of distribution at steady state 
 
 


 
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15.12.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
NONE 
 
East 
 
 
NONMEM 
 
 
SAS 
 
 
WinNonlin 
 
 


 
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15.13. 
Appendix 13: List of Data Displays 
15.13.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.0010 to 1.xxxx 
1.0010 to 1.xxxx 
Efficacy 
2.0010 to 2.xxxx 
2.0010 to 2.xxxx 
Safety 
3.0010 to 3.xxxx 
3.0010 to 3.xxxx 
Pharmacokinetic 
4.0010 to 4.xxxx 
4.0010 to 4.xxxx 
Population Pharmacokinetic (PopPK) 
5.0010 to 5.xxxx 
5.0010 to 5.xxxx 
Pharmacodynamic and / or Biomarker 
6.0010 to 6.xxxx 
6.0010 to 6.xxxx 
Pharmacokinetic / Pharmacodynamic 
7.0010 to 7.xxxx 
7.0010 to 7.xxxx 
Patient reported outcome 
8.0010 to 8.xxxx 
8.0010 to 8.xxxx 
Section 
Listings 
ICH Listings 
1.0010 to 1.xxxx 
Other Listings 
30.0010 to 30.xxxx 
 
15.13.2. 
Mock Example Shell Referencing 
Non IDSL specifications will be referenced as indicated and if required example mock-up 
displays provided in Appendix 14: Example Mock Shells for Data Displays. 
 
Section 
Figure 
Table 
Listing 
Study Population 
POP_Fn 
POP_Tn 
POP_Ln 
Efficacy 
EFF_Fn 
EFF_Tn 
EFF_Ln 
Safety 
SAFE_Fn 
SAFE_Tn 
SAFE_Ln 
Pharmacokinetic 
PK_Fn 
PK_Tn 
PK_Ln 
Population Pharmacokinetic (PopPK) 
POPPK_Fn 
POPPK_Tn 
POPPK_Ln 
Pharmacodynamic and / or Biomarker 
PD_Fn 
PD_Tn 
PD_Ln 
Pharmacokinetic / Pharmacodynamic 
PKPD_Fn 
PKPD_Tn 
PK/PD_Ln 
Patient reported outcome 
PRO_Fn 
PRO_Tn 
PRO_Ln 
NOTES:  
• 
Non-Standard displays are indicated in the ‘IDSL /  Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’ 
 
15.13.3. 
Deliverables 
Delivery [Priority] [1] 
Description 
IA [X] 
Interim Analysis for IDMC 
Headline [X] 
Headline result for SAC 
SAC [X] 
Statistical Analysis Complete for [1] Primary Analysis and [2] End of Study 
analysis 
NOTES:  
1. 
Indicates priority (i.e. order) in which displays will be generated for the reporting effort 


 
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15.13.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.0010 
Full Analysis 
ES8 
Summary of Subject Status and Reason for Study Withdrawal 
ICH E3, FDAAA, EudraCT 
IA [1], Headline, 
SAC [1],SAC [2] 
1.0020 
Full Analysis 
SD4 
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment 
ICH E3 
IA [1], Headline, 
SAC [1] ,SAC 
[2] 
1.0030 
Screened 
ES6 
Summary of Screening Status and Reasons for Screen Failure 
Journal Requirements 
SAC [1] 
1.0040 
Enrolled 
NS1 
Summary of Number of Participants by Country and Site ID 
EudraCT/Clinical Operations.  
IA [1], SAC [1] 
Protocol Deviation 
1.0050 
Full Analysis 
DV1 
Summary of Important Protocol Deviations 
ICH E3 
SAC [1] ,SAC 
[2] 
1.0060 
Full Analysis 
IE1 
Summary of Inclusion/Exclusion Criteria Deviations 
 
SAC [1] 
Population Analysed 
1.0070 
Enrolled 
SP1 
Summary of Study Populations  
IDSL. 
Headline, SAC 
[1] 
Demographic and Baseline Characteristics 
1.0120 
Full Analysis 
DM1 
Summary of Demographic Characteristics 
ICH E3, FDAAA, EudraCT 
IA [1], Headline, 
SAC [1] 
1.0121 
Evaluable 
DM1 
Summary of Demographic Characteristics (Evaluable) 
ICH E3, FDAAA, EudraCT 
IA [1] 
1.0080 
Enrolled 
DM11 
Summary of Age Ranges 
EudraCT 
SAC [1] 
1.0090 
Full Analysis 
DM5 
Summary of Race and Racial Combinations 
ICH E3, FDA, FDAAA, EudraCT 
SAC [1] 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.0160 
Full Analysis 
DC2 
Summary of Disease Characteristics at Screening 
Include genetic characteristics 
IA [1], Headline, 
SAC [1] 
1.0161 
Evaluable 
DC2 
Summary of Disease Characteristics at Screening (Evaluable) 
 
IA [1] 
1.0100 
Full Analysis 
DC1 
Summary of Disease Characteristics at Initial Diagnosis 
 
SAC [1] 
Prior and Concomitant Medications 
1.0110 
Full Analysis 
MH1 
Summary of Current Medical Conditions 
ICH E3  
 
SAC [1], ,SAC 
[2] 
1.0130 
Full Analysis 
MH1 
Summary of Past Medical Conditions 
ICH E3  
Separate summaries for Current & Past 
conditions, if collected. 
SAC [1] 
1.0210 
Full Safety 
CM8 
Summary of Concomitant Medications  
ICH E3   include ‘medications taken on-
treatment (including those started prior 
to treatment), and ‘‘Medications that 
started on treatment’ See Table 1.0210 
produced by Veramed at IA)  
IA [1], SAC [1] 
,SAC [2] 
1.0140 
Full Safety 
CM1 
Summary of Prophylactic Medication for Infusion-Related 
Reactions by Drug Class and Drug Name 
Medication will be identified based on 
verbatim term, and the drug class will 
be based on the medication group in 
the excel file provided by Safety. 
SAC [1] ,SAC 
[2] 
1.0150 
Full Safety 
CM1 
Summary of Eye Medications by Drug Class and Drug Name 
Medication will be identified based on 
verbatim term, and the drug class will 
be based on the medication group in 
the excel file provided by Safety. 
SAC [1] 
1.0170 
Full Safety 
Mock-up 
POP_T1 
Summary of Percentage of Duration of Exposure on Steroid Eye 
Drop Use  
 
SAC [1] 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Prior and Follow-up Anti-Cancer Therapy 
1.0180 
Full Analysis 
CM8 
Summary of Prior Dictionary Coded Anti-Cancer Therapy 
 
Headline, SAC 
[1] 
1.0190 
Full Analysis 
programmi
ng note 
Summary of Prior Anti-Cancer Therapy by Drug Class of Agents 
See Table 1.0141 in BMA117159 
(primary_01). 
Headline, SAC 
[1] 
1.0200 
Full Analysis 
programmi
ng note 
Summary of Subjects Refractory to Prior Anti-Cancer Therapy 
by Drug Class of Agents 
See Table 1.0151 in BMA117159 
(primary_01). 
Headline, SAC 
[1] 
1.0220 
Full Analysis 
AC3 
Summary of Number of Prior Anti-Cancer Therapy Regimens 
 
IA [1], SAC [1] 
1.0230 
Full Analysis 
AC4 
Summary of Best Response to Most Recent Prior Anti-Cancer 
Therapy 
 
SAC [1] 
1.0240 
Full Analysis 
FAC1 
Summary of Follow-Up Anti-Cancer Therapy 
 
SAC [1] 
Prior Surgical Procedures 
1.0250 
Full Analysis 
OSP2 
Summary of Prior Cancer and Non-Cancer Related Surgical 
Procedures 
 
SAC [1] 
Exposure and Treatment Compliance 
1.0300 
Full Safety 
OEX5 
Summary of Exposure to GSK2857916 
ICH E3; by number of cycles, and 
included the summary of dose intensity 
(mg/kg per 3 weeks) 
IA [1], Headline, 
SAC [1] ,SAC 
[2] 
1.0301 
Evaluable 
OEX5 
Summary of Exposure to Study Treatment (Evaluable) 
ICH E3; by number of cycles 
IA [1] 
1.0260 
Full Safety 
OEX1 
Summary of Duration of Exposure to GSK2857916 
Only include “Time on Study Treatment; 
Mean, median, SD, Min, Max of 
duration in weeks 
Headline, SAC 
[1] ,SAC [2] 
1.0270 
Full Safety 
OEX6 
Summary of Dose of GSK2857916 delivered by Cycle 
 
SAC [1] ,SAC 
[2] 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.0280 
Full Safety 
ODMOD1 
Summary of Dose Reductions of GSK2857916 
 
Headline, SAC 
[1] ,SAC [2] 
1.0290 
Full Safety 
ODMOD3 
Summary of Dose Delays of GSK2857916 
 
Headline, SAC 
[1] ,SAC [2] 
1.0310 
Full Safety 
ODMOD5 
Summary of Primary Reason for Dose Reductions of 
GSK2857916 by Cycle 
 
SAC [1] ,SAC 
[2] 
1.0320 
Full Safety 
ODMOD6 
Summary of Primary Reason for Dose Delays of GSK2857916 
by Cycle 
 
SAC [1] ,SAC 
[2] 
1.1114
0 
Full Safety 
OEX1 
Summary of Duration of Exposure to GSK2857916 by Response 
Category Based on Independent Reviewer-Assessed Response 
 
SAC [2] 
Duration of Follow-up 
1.0330 
Full Analysis 
FAC2 
Summary of Duration of Follow-Up 
 
SAC [1] ,SAC 
[2] 
Blood and Blood Supportive Care Products 
1.0340 
Full Analysis 
BP1A 
Summary of Blood Products 
 
SAC [1] 
1.0350 
Full Analysis 
BP1C 
Summary of Blood Supportive Care Products 
 
SAC [1] 
Substance Use 
1.0360 
Full Analysis 
SU1 
Summary of Substance Use 
 
SAC [1] 
 


 
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15.13.5. 
Study Population Figures 
Study Population: Figures 
No. 
Population 
IDSL /  
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Exposure 
1.0010 
Full Safety 
programmi
ng note 
Plot of Dose Reduction of GSK2857916 by Cycle 
See Figure 11.0020 in BMA117159 
(primary_01). 
Headline, SAC 
[1] ,SAC [2] 
1.0020 
Full Safety 
OEX12 
Plot of Duration of Study Treatment by Response 
Split page by dose arm 
SAC [1] ,SAC 
[2] 
1.00010 
Safety 
Programm
ing note 
Graph of Kaplan Meier Curves of Time to Treatment 
Discontinuation by Response Category Based on 
Independent Reviewer-Assessed Response 
Refer regqry_2020_10 
SAC [2] 
1.00011 
Safety 
Programm
ing note 
Graph of Kaplan Meier Curves of Time to Treatment 
Discontinuation in Subjects Receiving at least 3 Cycles of 
GSK2857916 
Refer regqry_2020_10 
SAC [2] 
1.00013 
Safety 
Programm
ing note 
Graph of Kaplan Meier Curves of Time to Treatment 
Discontinuation 
Refer present_2020_04 
SAC [2] 
COVID-19 
1.0082 
Full Safety 
PAN8 
Visits Impacted by COVID-19 Pandemic 
 
SAC [2] 
 
 


 
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15.13.6. 
Efficacy Tables 
Efficacy: Tables 
No. 
Population 
IDSL /  
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Response 
2.0010 
Full Analysis 
RE1a 
Summary of Independent Reviewer-Assessed Best Response 
with Confirmation 
 
Headline, SAC [1] 
,SAC [2] 
2.0011 
Efficacy 
RE1a 
Summary of Independent Reviewer-Assessed Best Response 
with Confirmation 
 
Headline, SAC [1] 
,SAC [2] 
2.0020 
Full Analysis 
RE1a 
Summary of Investigator-Assessed Best Response with 
Confirmation 
 
Headline, SAC [1] 
2.0021 
Efficacy 
RE1a 
Summary of Investigator-Assessed Best Response with 
Confirmation 
 
Headline, SAC [1] 
2.0030 
Evaluable 
RE1a 
Summary of Investigator-Assessed Best Response for Interim 
Futility Analyses 
 
IA [1] 
2.0040 
Full Analysis 
Mock up 
EFF_T1 
Summary of MRD Negativity Rate by Best Response  
MRD negativity will be based on test 
result with sensitivity of 10^5. 
SAC [1] ,SAC [2] 
2.0050 
Full Analysis 
RE3 
Summary of Independent Reviewer-Assessed and Investigator-
Assessed Best Response with Confirmation 
The response categories are: sCR, 
CR, VGPR, PR, MR, SD, PD, NE. 
One Table for 2.5mg, and one Table 
for 3.4mg 
SAC [1] 
Time-to-Event 
2.0060 
Full Analysis 
TTE1a 
Summary of Duration of Response Based on Independent 
Reviewer-Assessed Response 
 
Headline, SAC 
[1],SAC [2] 
2.0061 
Efficacy 
TTE1a 
Summary of Duration of Response Based on Independent 
Reviewer-Assessed Response 
 
Headline, SAC 
[1],SAC [2] 


 
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Efficacy: Tables 
No. 
Population 
IDSL /  
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.0062 
Full Analysis 
TTE1a 
Summary of Duration of Response Based on Independent 
Reviewer - Assessed Response II 
Include probability of Maintaining 
Response at different time points, and 
Hazard ratio estimated by Pike 
estimator. 
SAC [2] 
2.0070 
Full Analysis 
TTE1a 
Summary of Duration of Response Based on Investigator-
Assessed Response 
 
Headline, SAC [1] 
2.0071 
Efficacy 
TTE1a 
Summary of Duration of Response Based on Investigator-
Assessed Response 
 
Headline, SAC [1] 
2.0080 
Full Analysis 
TTE1a 
Summary of Progression-Free Survival Based on Independent 
Reviewer-Assessed Response 
Include the estimated PFS probability 
at Month 6. 
Headline, SAC 
[1], SAC [2] 
2.0090 
Full Analysis 
TTE1a 
Summary of Progression-Free Survival Based on Investigator-
Assessed Response 
 
Headline, SAC [1] 
2.0100 
Full Analysis 
TTE1a 
Summary of Time to Progression Based on Independent 
Reviewer-Assessed Response 
 
SAC [1], SAC [2] 
2.0110 
Full Analysis 
TTE1a 
Summary of Time to Progression Based on Investigator-
Assessed Response 
 
SAC [1] 
2.0120 
Full Analysis 
TTE1a 
Summary of Time to Response Based on Independent 
Reviewer-Assessed Response 
Among responders only 
SAC [1], SAC [2] 
2.0121 
Efficacy 
TTE1a 
Summary of Time to Response Based on Independent 
Reviewer-Assessed Response 
Among responders only 
SAC [1], SAC [2] 
2.0130 
Full Analysis 
TTE1a 
Summary of Time to Response Based on Investigator-
Assessed Response 
Among responders only 
SAC [1] 
2.0131 
Efficacy 
TTE1a 
Summary of Time to Response Based on Investigator-
Assessed Response 
Among responders only 
SAC [1] 


 
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Efficacy: Tables 
No. 
Population 
IDSL /  
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.0140 
Full Analysis 
Mock up 
EFF_T2 
Summary of Reasons for Censoring 
 
SAC [1] 
2.0150 
Full Analysis 
TTE1a 
Summary of Overall Survival 
Include the estimated overall survival 
probability at Month 6 at primary 
analysis; add estimated overall 
survival probability at Month 12 at 
90D Safety Update. 
SAC [1], SAC [2] 
2.0160 
Full Analysis 
TTE1a 
Summary of Duration of MRD Negativity 
MRD negativity will be based on test 
result with sensitivity of 10^5.Pending 
on amount of data available 
SAC [1] 
2.0170 
Full Analysis 
Programmi
ng note 
Response, Adverse Events, and Dose Modifications by Dose 
Level 
Use Table S4 in manuscript 
(https://ars.els-
cdn.com/content/image/1-s2.0-
S147020451830576X-mmc1.pdf) for 
BMA117159 as mock-up. 
Headline, SAC [1] 
2.1001
0 
ITT 
TTE1a 
Summary of Time to Best Response Based on Independent 
Reviewer - Assessed Response 
 
SAC [2] 
2.1004
0 
ITT 
TTE1a 
Summary of Progression-Free Survival by Response Category 
Based on Independent Reviewer-Assessed Response 
 
SAC [2] 
2.1004
1 
FSAFL 
TTE1a 
Summary of Progression-Free Survival by Response Category 
Based on Independent Reviewer-Assessed Response 
 
SAC [2] 
2.1005
0 
ITT 
TTE1a 
Summary of Overall Survival by Response Category Based on 
Independent Reviewer-Assessed Response 
 
SAC [2] 
 
 
 


 
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15.13.7. 
Efficacy Figures 
Efficacy: Figures 
No. 
Populat
ion 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Response 
2.0010 
ITT 
Programming 
note 
Forest Plot - Overall Response Rate (ORR) Based on 
Independent Reviewer-Assessed Response 
Similar to Figure 12.012 in BMA117159 
(primary_01). See Section 5.3.2 for the 
subgroups to be included.  
Headline, SAC [1], 
SAC [2] 
2.0020 
ITT 
 Programming 
note 
Forest Plot - Overall Response Rate (ORR) Based on 
Investigator-Assessed Response 
Similar to Figure 12.012 in BMA117159 
(primary_01). See Section 5.3.2 for the 
subgroups to be included. 
Headline, SAC [1] 
2.0030 
Full 
Analysis 
RE8b 
Percent Change at Maximum Reduction from Baseline in M-
Protein (or FLC) Measurement 
 
Headline, SAC [1] 
Time-to-Event 
2.0040 
ITT 
TTE10 
Graph of Kaplan Meier Curves of Duration of Response Based 
on Independent Reviewer-Assessed Response 
 
Headline, SAC [1], 
SAC [2] 
2.0041 
Efficacy 
TTE10 
Graph of Kaplan Meier Curves of Duration of Response Based 
on Independent Reviewer-Assessed Response 
 
Headline, SAC [1], 
SAC [2] 
2.0050 
ITT 
TTE10 
Graph of Kaplan Meier Curves of Duration of Response Based 
on Investigator-Assessed Response 
 
Headline, SAC [1] 
2.0051 
Efficacy 
TTE10 
Graph of Kaplan Meier Curves of Duration of Response Based 
on Investigator-Assessed Response 
 
Headline, SAC [1] 
2.0060 
ITT 
TTE10 
Graph of Kaplan Meier Curves of Progression-Free Survival 
Based on Independent Reviewer-Assessed Response 
 
Headline, SAC [1], 
SAC [2] 
2.0070 
ITT 
TTE10 
Graph of Kaplan Meier Curves of Progression-Free Survival 
Based on Investigator-Assessed Response 
 
Headline, SAC [1] 
2.0080 
ITT 
TTE10 
Graph of Kaplan Meier Curves of Time to Progression Based 
on Independent Reviewer-Assessed Response 
 
SAC [1], SAC [2] 


 
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Efficacy: Figures 
No. 
Populat
ion 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
2.0090 
ITT 
TTE10 
Graph of Kaplan Meier Curves of Time to Progression Based 
on Investigator-Assessed Response 
 
SAC [1] 
2.0100 
ITT 
TTE10 
Graph of Kaplan Meier Curves of Overall Survival 
 
SAC [1], SAC [2] 
2.00402 
ITT 
Programming 
note 
Graph of Kaplan Meier Curves of Duration of Response by 
Dose Delay Category Based on Independent Reviewer - 
Assessed Response 
Refer regqry_2020_10 
SAC [2] 
2.10010 
ITT 
Programming 
note 
Graph of Kaplan Meier Curves of Progression-Free Survival by 
Response Category Based on Independent Reviewer-
Assessed Response 
Refer regqry_2020_10 
SAC [2] 
2.10020 
ITT 
Programming 
note 
Graph of Kaplan Meier Curves of Overall Survival by Response 
Category Based on Independent Reviewer-Assessed 
Response 
Refer  regqry_2020_10 
SAC [2] 
2.10080 
ITT 
Programming 
note 
Graph of Kaplan Meier Curves of Duration of Response by 
Response Category Based on Independent Reviewer-
Assessed Response 
Refer  regqry_2020_10 
SAC [2] 
2.30305 
Full 
Safety  
Programming 
note 
Profile Plot of Patients with Corneal Events (GSK Scale) 
Refer  present_2020_04 
SAC [2] 
2.70033 
ITT 
Programming 
note 
Swim-lane Plot of Duration of Study Treatment for Responder 
Based on Independent Reviewer-Assessed Response 
Refer  regqry_2020_10 
SAC [2] 
 


 
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15.13.8. 
Safety Tables 
Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Adverse Events (AEs) 
3.0010 
Full Safety 
AE13 
Adverse Event Overview 
Compared to what was delivered at IA, 
add two more categories: Grade 3&4 
AEs, Grade 3&4 AEs related to study 
treatment, 
IA [1], Headline, 
SAC [1] , SAC 
[2] 
3.0011 
Evaluable  
AE13 
Adverse Event Overview (Evaluable) 
 
IA [1] 
3.0020 
Full Safety 
AE1 
Summary of All Adverse Events by System Organ Class 
and Preferred Term 
ICH E3 
See version created at IA 
IA [1], SAC [1] , 
SAC [2] 
3.0030 
Full Safety 
AE3 
Summary of All Adverse Events by Preferred Term 
 
SAC [1] 
3.0040 
Full Safety 
OAE07 
Summary of All Adverse Events by Preferred Term and 
Maximum Grade 
 
IA [1], Headline, 
SAC [1] , SAC 
[2] 
3.0041 
Evaluable 
OAE07 
Summary of All Adverse Events by Preferred Term and 
Maximum Grade (Evaluable) 
 
IA [1] 
3.0050 
Full Safety 
AE3 
Summary of Common (>=5%) Adverse Events by Preferred 
Term 
ICH E3 
SAC [1] 
3.0060 
Full Safety 
AE3 
Summary of Common (>=5%) Grade 2-4 Adverse Events 
by Preferred Term 
ICH E3 
SAC [1] 
3.0070 
Full Safety 
AE1 
Summary All Drug-Related Adverse Events by System 
Organ Class and Preferred Term 
ICH E3 
SAC [1] 
3.0080 
Full Safety 
OAE07 
Summary of All Drug-Related Adverse Events by Preferred 
Term and Maximum Grade  
 
SAC [1] 


 
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Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.0090 
Full Safety 
AE15 
Summary of Common (>=5%) Non-serious Adverse Events 
by System Organ Class and Preferred Term (Number of 
Participants and Occurrences) 
FDAAA, EudraCT 
SAC [1] 
3.0100 
Full Safety 
AE3 
Summary of Common (>=5%) Drug-Related Grade 2-4 
Adverse Events by Preferred Term 
ICH E3 
SAC [1] , SAC 
[2] 
3.0110 
Full Safety 
AE3 
Summary of Adverse Events of Maximum Grade 3 or 
Higher by Preferred Term 
 
Headline, SAC 
[1] , SAC [2] 
3.0560 
Full Safety 
AE6 
Summary of Cumulative Incidence of Adverse Events by PT 
and Number of Doses Received at First Occurrence 
Only PT term, no SOC needed. The 
number of doses received at first 
occurrence will be <= 1, <= 2, <= 4, <= 
6, <= 8, <= 10, and Any 
SAC [1] 
3.0570 
Full Safety 
AE3 
Summary of Non-Serious Drug-related Adverse Events by 
Preferred Term 
 
SAC [1] 
Serious and Other Significant Adverse Events 
3.0120 
Full Safety 
AE16 
Summary of Serious Adverse Events by System Organ 
Class and Preferred Term (Number of Participants and 
Occurrences) 
FDAAA, EudraCT 
IA [1], SAC [1] 
3.0580 
Full Safety 
AE3 
Summary of Serious Adverse Events by Preferred Term  
 
Headline, SAC 
[1],SAC [2] 
3.0130 
Full Safety 
AE3 
Summary of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment by Preferred Term 
 
IA [1], Headline, 
SAC [1] , SAC 
[2] 
3.0140 
Full Safety 
AE3 
Summary of All Serious Drug-Related Adverse Events by 
Preferred Term 
 
SAC [1] , SAC 
[2] 
3.0150 
Full Safety 
AE3 
Summary of Adverse Events Leading to Dose Reduction by 
Preferred Term  
 
Headline, SAC 
[1] , SAC [2] 


 
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102 
Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.0160 
Full Safety 
AE3 
Summary of Adverse Events Leading to Dose Delays by 
Preferred Term 
 
Headline, SAC 
[1] , SAC [2] 
3.0830 
Full Safety 
AE6 
Summary of Cumulative Incidence of Serious Adverse 
Events by PT and Number of Doses Received at First 
Occurrence 
Only PT term, no SOC needed. The 
number of doses received at first 
occurrence will be <= 1, <= 2, <= 4, <= 
6, <= 8, <= 10, and Any 
SAC [1] ,SAC 
[2] 
AEs of Special Interest 
3.0170 
Full Safety 
OAE07 
Summary of Keratopathy Events (CTCAE) by Preferred 
Term and Maximum Grade 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1] , SAC 
[2] 
3.0171 
Evaluable 
OAE07 
Summary of Dry Eye Events (CTCAE) by Preferred Term 
and Maximum Grade (Evaluable) 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1] , SAC 
[2] 
3.0172 
Full Safety 
OAE07 
Summary of Blurred Vision Event (CTCAE) by Preferred 
Term and Maximum Grade 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1] , SAC 
[2] 
3.0173 
Full Safety 
OAE07 
Summary of Photophobia Event (CTCAE) by Preferred 
Term and Maximum Grade 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1] 
3.0174 
Full Safety 
OAE07 
Summary of Eye Pain Event (CTCAE) by Preferred Term 
and Maximum Grade 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1] 
3.0180 
Full Safety 
ESI1 
Summary of Characteristics of Keratopathy Events 
(CTCAE) 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. Include 
summary of outcome of AE.  
SAC [1] , SAC 
[2] 


 
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103 
Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.0181 
Full Safety 
ESI1 
Summary of Characteristics of Dry Eye Events (CTCAE) 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. Include 
summary of outcome of AE 
SAC [1] , SAC 
[2] 
3.0182 
Full Safety 
ESI1 
Summary of Characteristics of Blurred Vision Events 
(CTCAE) 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. Include 
summary of outcome of AE 
SAC [1] , SAC 
[2] 
3.0183 
Full Safety 
ESI1 
Summary of Characteristics of Photophobia Events 
(CTCAE) 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. Include 
summary of outcome of AE 
SAC [1] 
3.0184 
Full Safety 
ESI1 
Summary of Characteristics of Eye Pain Events (CTCAE) 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. Include 
summary of outcome of AE 
SAC [1] 
3.0200 
Full Safety 
Mock-up 
SAFE_T21 
Summary of Keratopathy Events (CTCAE) Characteristics II  
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1]  
3.0201 
Full Safety 
Mock-up 
SAFE_T21 
Summary of Dry Eye Events (CTCAE) Characteristics II  
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1] , SAC 
[2] 
3.0202 
Full Safety 
Mock-up 
SAFE_T21 
Summary of Blurred Vision Events (CTCAE) Characteristics 
II  
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1], SAC 
[2] 
3.0203 
Full Safety 
Mock-up 
SAFE_T21 
Summary of Photophobia Events (CTCAE) Characteristics 
II  
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1] 


 
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104 
Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.0204 
Full Safety 
Mock-up 
SAFE_T21 
Summary of Eye Pain Events (CTCAE) Characteristics II  
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1] 
3.0250 
Full Safety 
AE13 
Overview of Eye Disorder (CTCAE) 
Same categories as AE overview 
 SAC [1] , SAC 
[2] 
3.0251 
Full Safety 
AE13 
Overview of Keratopathy Event (CTCAE) 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. Same 
categories as AE overview 
 SAC [1], , SAC 
[2] 
3.0252 
Full Safety 
AE13 
Overview of Dry Eye Event (CTCAE) 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. Same 
categories as AE overview 
 SAC [1], , SAC 
[2] 
3.0253 
Full Safety 
AE13 
Overview of Blurred Vision Event (CTCAE) 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. Same 
categories as AE overview 
 SAC [1] , SAC 
[2] 
3.0250 
Full Safety 
AE13 
Overview of Photophobia Event (CTCAE) 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. Same 
categories as AE overview 
 SAC [1] 
3.0250 
Full Safety 
AE13 
Overview of Eye Pain Event (CTCAE) 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. Same 
categories as AE overview 
 SAC [1]  
3.1320 
Full Safety 
Mock-up 
SAFE_T22 
Summary of Percentage of Duration of Exposure with 
Keratopathy Events (CTCAE)  
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1], SAC 
[2] 


 
CONFIDENTIAL 
 
 
 
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105 
Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.1321 
Full Safety 
Mock-up 
SAFE_T22 
Summary of Percentage of Duration of Exposure with Dry 
Eye Events (CTCAE) 
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1], SAC 
[2] 
3.1322 
Full Safety 
Mock-up 
SAFE_T22 
Summary of Percentage of Duration of Exposure with 
Blurred Vision Events (CTCAE)  
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1], SAC 
[2] 
3.1323 
Full Safety 
Mock-up 
SAFE_T22 
Summary of Percentage of Duration of Exposure with 
Photophobia Events (CTCAE)  
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1] 
3.1324 
Full Safety 
Mock-up 
SAFE_T22 
Summary of Percentage of Duration of Exposure with Eye 
Pain Events (CTCAE)  
Table need to be created only if the 
observed incidence rate >= 10% in 3.4 
mg/kg Frozen liquid cohort. 
SAC [1] 
3.0270 
Full Safety 
OAE07 
Summary of Thrombocytopenia by Preferred Term and 
Maximum Grade 
 
IA [1], SAC [1] , 
SAC [2] 
3.0271 
Evaluable 
OAE07 
Summary of Thrombocytopenia by Preferred Term and 
Maximum Grade (Evaluable) 
 
IA [1] 
3.0280 
Full Safety 
ESI1 
Summary of Characteristics of Thrombocytopenia 
Include summary outcome of AE;  
IA [1], SAC [1] , 
SAC [2] 
3.0290 
Full Safety 
ESI2b 
Summary of Onset and Duration of the First Occurrence of 
Thrombocytopenia 
Algorithm of duration calculation need 
to be updated to follow what was done 
in T3.1171 in 117159 (Primary_02).  
IA [1], SAC [1], 
SAC [2] 
3.0300 
Full Safety 
OAE07 
Summary of Infusion-Related Reactions by Preferred Term 
and Maximum Grade 
 
IA [1], Headline, 
SAC [1] ], SAC 
[2] 
3.0301 
Evaluable 
OAE07 
Summary of Infusion-Related Reactions by Preferred Term 
and Maximum Grade (Evaluable) 
 
IA [1] 


 
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205678 
 
106 
Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.0320 
Full Safety 
ESI1 
Summary of Characteristics of Infusion-Related Reactions 
Include summary of outcome of AE;  
IA [1], Headline, 
SAC [1] ], SAC 
[2] 
3.0330 
Full Safety 
ESI2b 
Summary of Onset and Duration of the First Occurrence of 
Infusion-Related Reactions 
Algorithm of duration calculation need 
to be updated to follow what was done 
in T3.1171 in 117159 (Primary_02). 
IA [1], Headline, 
SAC [1],SAC [2] 
3.0870 
Full Safety 
OAE07 
Summary of Neutropenia by Preferred Term and Maximum 
Grade 
 
IA [1], SAC [1] 
,SAC [2] 
3.0880 
Full Safety 
ESI1 
Summary of Characteristics of Neutropenia 
Include summary of outcome of AE;  
IA [1], SAC [1] 
,SAC [2] 
3.0890 
Full Safety 
ESI2b 
Summary of Onset and Duration of the First Occurrence of 
Neutropenia 
Algorithm of duration calculation need 
to be updated to follow what was done 
in T3.1171 in 117159 (Primary_02). 
IA [1], SAC [1] 
,SAC [2] 
3.0900 
Full Safety 
AE13 
Corneal Event (GSK Scale) Overview 
including n (%) of subjects with any 
event IGSK scale), event related to 
study treatment, Grade 3&4 AEs, 
Grade 3&4 AEs related to study 
treatment, event leading to permanent 
discontinuation of study treatment, 
event leading to dose reductions, event 
leading to dose delays 
Headline, SAC 
[1] ,SAC [2] 
3.0340 
Full Safety 
Mock-up 
SAFE_T1 
Summary of Corneal Events (GSK Scale) by Grade and 
Visit  
 Add footnote that Visits ‘Cycle 1-4 Day 
1/Day 10’ are from ocular sub-study 
subjects only. 
SAC [1], SAC 
[2] 
3.0350 
Full Safety 
ESI1 
Summary of Characteristics of Corneal Events (GSK Scale) 
Include summary of outcome of AE; 
Headline, SAC 
[1] , SAC [2] 


 
CONFIDENTIAL 
 
 
 
205678 
 
107 
Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.0360 
Full Safety 
ESI2b 
Summary of Onset and Duration of the First Occurrence of 
Corneal Events (GSK Scale) of Grade 3 or Above 
Algorithm of duration calculation need 
to be updated to follow what was done 
in T3.1171 in 117159 (Primary_02). 
SAC [1] , SAC 
[2] 
3.0910 
Full Safety 
ESI2b 
Summary of Onset and Duration of the First Occurrence of 
Corneal Events (GSK Scale) of Grade 2 or Above 
Algorithm of duration calculation need 
to be updated to follow what was done 
in T3.1171 in 117159 (Primary_02). 
Headline, SAC 
[1] ,SAC [2] 
3.0911 
Full Safety 
Mock-up 
SAFE_T21 
Summary of Characteristics II of Corneal Events (GSK 
Scale) of Grade 2 or Above 
 
SAC [1] ,SAC 
[2] 
3.0912 
Full Safety 
Mock-up 
SAFE_T21 
Summary of Characteristics II of Visual Acuity (GSK Scale) 
of Grade 2 or Above 
 
SAC [1] ,SAC 
[2] 
3.0370 
Full Safety 
Mock-up 
SAFE_T2a 
Summary of Corneal Events (GSK Scale) Leading to Action 
Taken with Study Treatment 
 
SAC [1] , SAC 
[2] 
3.0380 
Full Safety 
Mock-up 
SAFE_T2 
Summary of Action Taken with Study Treatment for Corneal 
Events (GSK Scale) by Visit 
No need to include EOT visit. Add 
footnote that Visits ‘Cycle 1-4 Day 
1/Day 10’ are from ocular sub-study 
subjects only. 
SAC [1] , SAC 
[2] 
3.0410 
Full Safety 
Mock-up 
SAFE_T3 
Shift in Grade of Corneal Events (GSK Scale) from EOT to 
Last Follow-Up 
 
SAC [1] , SAC 
[2] 
3.0420 
Full Safety 
Mock-up 
SAFE_T4a 
Summary of resolution in Grade of Corneal Events (GSK 
Scale) from EOT to last Follow-Up. 
 
SAC [1] , SAC 
[2] 
3.0430 
Full Safety 
Mock-up 
SAFE_T4b 
Summary of Time to Re-initiation of Study Treatment Post 
Treatment Delay due to Corneal Events (GSK Scale) 
 
SAC [1] , SAC 
[2] 
3.0440 
Evaluable 
Programming 
note 
Summary of Worst Post-Baseline Corneal Findings (GSK 
Scale) Evaluable 
This table was already produced by 
Veramed at IA  
IA [1] 


 
CONFIDENTIAL 
 
 
 
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108 
Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.0441 
 
Full Safety 
Programming 
note 
Summary of Worst Post-Baseline Corneal Events (GSK 
Scale) 
Could also use T3.0440 produced by 
Veramed at IA as template. 
SAC [1] 
3.0920 
 
Full Safety 
Programming 
note 
Summary of Worst Post-Baseline Corneal Events (GSK 
Scale) by Best Response Based on Independent Review 
Committee 
Best Response categories: 
(PR/VGPR/CR/sCR vs. otherwise). 
Could also use T3.0440 produced by 
Veramed at IA as template. 
SAC [1] ,SAC 
[2] 
3.1330 
Full Safety Mock-up 
SAFE_T22 
Summary of Percentage of Duration of Exposure with 
Corneal Events (GSK scale) Grade >= 2  
 
SAC [1], SAC 
[2] 
3.1331 
Full Safety Mock-up 
SAFE_T22 
Summary of Percentage of Duration of Exposure with 
Corneal Events (GSK scale) Grade >= 3 
  
SAC [1], SAC 
[2] 
3.0950 
Full Safety AE6 
Summary of Cumulative Incidence of Keratopathy Event 
(CTCAE) by PT and Number of Doses Received at First 
Occurrence 
Only PT term, no SOC needed. The 
number of doses received at first 
occurrence will be <= 1, <= 2, <= 4, <= 
6, <= 8, <= 10, and Any 
SAC [1] ,SAC 
[2] 
3.0951 
Full Safety AE6 
Summary of Cumulative Incidence of Dry Eye Event 
(CTCAE) by PT and Number of Doses Received at First 
Occurrence 
Only PT term, no SOC needed. The 
number of doses received at first 
occurrence will be <= 1, <= 2, <= 4, <= 
6, <= 8, <= 10, and Any 
SAC [1] ,SAC 
[2] 
3.0952 
Full Safety AE6 
Summary of Cumulative Incidence of Blurred Vision Event 
(CTCAE) by PT and Number of Doses Received at First 
Occurrence 
Only PT term, no SOC needed. The 
number of doses received at first 
occurrence will be <= 1, <= 2, <= 4, <= 
6, <= 8, <= 10, and Any 
SAC [1] ,SAC 
[2] 
3.0953 
Full Safety AE6 
Summary of Cumulative Incidence of Photophobia Event 
(CTCAE) by PT and Number of Doses Received at First 
Occurrence 
Only PT term, no SOC needed. The 
number of doses received at first 
occurrence will be <= 1, <= 2, <= 4, <= 
6, <= 8, <= 10, and Any 
SAC [1] 


 
CONFIDENTIAL 
 
 
 
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109 
Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.0954 
Full Safety AE6 
Summary of Cumulative Incidence of Eye Pain Event 
(CTCAE) by PT and Number of Doses Received at First 
Occurrence 
Only PT term, no SOC needed. The 
number of doses received at first 
occurrence will be <= 1, <= 2, <= 4, <= 
6, <= 8, <= 10, and Any 
SAC [1] 
3.0960 
Full Safety AE6 
Summary of Cumulative Incidence of Thrombocytopenia by 
PT and Number of Doses Received at First Occurrence 
Only PT term, no SOC needed. The 
number of doses received at first 
occurrence will be <= 1, <= 2, <= 4, <= 
6, <= 8, <= 10, and Any 
SAC [1] ,SAC 
[2] 
3.0990 
Full Safety AE6 
Summary of Cumulative Incidence of Neutropenia by PT 
and Number of Doses Received at First Occurrence 
Only PT term, no SOC needed. The 
number of doses received at first 
occurrence will be <= 1, <= 2, <= 4, <= 
6, <= 8, <= 10, and Any 
SAC [1] ,SAC 
[2] 
3.1030 
Full Safety AE6 
Summary of Cumulative Incidence of Infusion-Related 
Reactions by PT and Number of Doses Received at First 
Occurrence 
Only PT term, no SOC needed. The 
number of doses received at first 
occurrence will be <= 1, <= 2, <= 4, <= 
6, <= 8, <= 10, and Any 
SAC [1], ,SAC 
[2] 
3.1210 
Full Safety Mock-up 
SAFE_T1a 
Summary of Cumulative Incidence of Corneal Events (GSK 
Scale) by Grade and Number of Doses Received at First 
Occurrence 
 
SAC [1] ,SAC 
[2] 
3.1203
0 
Full Safety ESI2b 
Summary of Blurred Vision and Dry Eye Events versus 
GSK Scale 
 
SAC [2] 
3.1280 
Safety 
Mock-up 
SAFE_T5 
Logistic Regression Analysis of Possible Risk Factors for 
Developing Corneal Events Grade >=2 (GSK Scale) 
See Section 8.2.2 Item 9 for details. 
SAC [1], SAC 
[2] 
3.1290 
Full Safety Mock-up 
SAFE_T11 
Summary of Thrombocytopenia and Bleeding Event 
 
SAC [1], SAC 
[2] 


 
CONFIDENTIAL 
 
 
 
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110 
Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.1246
1 
Full Safety OAE07 
Summary of Eye Disorder Events (CTCAE) with Dose 
Delays by Preferred Term and Maximum Grade 
 
SAC [2] 
3.1247
1 
Full Safety 
Programming 
note 
Summary of Ocular Symptoms and Visual Acuity Change 
(GSK Scale) by Worst Grade of Keratopathy 
Refer regqry_2020_10 
SAC [2] 
3.1247
2 
Full Safety 
Programming 
note 
Summary of Ocular Symptoms and Visual Acuity Change 
(GSK Scale) by Worst Grade of Corneal Events (GSK 
Scale) 
Refer regqry_2020_10 
SAC [2] 
3.1247
3 
Full Safety 
Programming 
note 
Summary of Ocular Symptoms and Visual Acuity Change 
(>=2 lines in Better Eye) by Worst Grade of Corneal Exam 
Finding 
Refer regqry_2020_10 
SAC [2] 
3.1248
0 
Full Safety OAE07 
Summary of Eye Disorder Events (CTCAE) Leading to 
Dose Delays by Preferred Term and Maximum Grade 
Refer regqry_2020_04 
SAC [2] 
3.1249
0 
Full Safety 
Programming 
note 
Summary of Subjects with Dose Delay due to Eye Disorder 
Events (CTCAE) at the Time of Data Cutoff 
Refer regqry_2020_04 
SAC [2] 
3.1273
1 
Full Safety 
Programming 
note 
Summary of Vision Blurred, and Dry Eye by Preferred Term 
in Subjects with Keratopathy 
Refer regqry_2020_08 
SAC [2] 
3.1273
5 
Full Safety 
Programming 
note 
Summary of Vision Blurred, and Dry Eye by Preferred Term 
and Maximum Grade in Subjects with Keratopathy 
Refer regqry_2020_08 
SAC [2] 
3.12737 
Full Safety 
Programming 
note 
Summary of Ocular Symptoms (CTCAE) by Preferred Term 
and Maximum Grade in Subjects with Keratopathy 
Refer regqry_2020_10 
SAC [2] 


 
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111 
Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.1273
8 
Full Safety 
Programming 
note 
Summary of Ocular Symptoms (CTCAE) by Preferred Term 
and Maximum Grade 
Refer regqry_2020_08 
SAC [2] 
3.1275
1 
Full Safety 
Programming 
note 
Summary of Blurred Vision and Dry Eye Events versus 
Keratopathy 
Refer regqry_2020_08 
SAC [2] 
3.1275
3 
Full Safety 
Programming 
note 
Summary of Ocular Symptoms (CTCAE) versus 
Keratopathy 
Refer regqry_2020_08 
SAC [2] 
3.1276
1 
Full Safety 
Programming 
note 
Summary of Duration of Keratopathy with Concurrent 
Blurred Vision or Dry Eye 
Refer regqry_2020_08 
SAC [2] 
3.1276
3 
Full Safety 
Programming 
note 
Summary of Duration of Keratopathy with Concurrent 
Ocular Symptoms (CTCAE) 
Refer regqry_2020_08 
SAC [2] 
3.1277
0 
Full Safety 
Programming 
note 
Summary of GSK scale Events Characteristics II 
Refer regqry_2020_10 
SAC [2] 
3.1277
1 
Full Safety 
Programming 
note 
Summary of Corneal Exam Finding (GSK scale) 
Characteristics II 
Refer regqry_2020_10 
SAC [2] 
3.1277
2 
Full Safety 
Programming 
note 
Summary of Visual Acuity Change (GSK scale) 
Characteristics II 
Refer regqry_2020_10 
SAC [2] 
3.1277
3 
Full Safety 
Programming 
note 
Summary of Maximum Grade for Corneal Exam Finding 
(GSK scale) 
Refer regqry_2020_10 
SAC [2] 
3.1277
4 
Full Safety 
Programming 
note 
Summary of Maximum Grade for Visual Change (GSK 
scale) 
Refer regqry_2020_10 
SAC [2] 


 
CONFIDENTIAL 
 
 
 
205678 
 
112 
Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.1278
1 
Full Safety 
Programming 
note 
Summary of Worsening in Best Corrected Visual Acuity 
(BCVA) Score (logMAR Score) Characteristics II 
Refer regqry_2020_08 
SAC [2] 
3.1279
1 
Full Safety 
Programming 
note 
Summary of Blurred Vision and Dry Eye Event 
Characteristics II in Subjects with Keratopathy 
Refer  regqry_2020_10 
SAC [2] 
3.1279
3 
Full Safety 
Programming 
note 
Summary of Ocular Symptoms (CTCAE) Event 
Characteristics II in Subjects with Keratopathy 
Refer regqry_2020_10 
SAC [2] 
3.1280
1 
Full Safety 
Programming 
note 
Summary of Unilateral Worsening in Best Corrected Visual 
Acuity (BCVA) to 20/50 or Worse Characteristics II 
Refer regqry_2020_08 
SAC [2] 
3.1281
1 
Full Safety 
Programming 
note 
Summary of Bilateral Worsening in Best Corrected Visual 
Acuity (BCVA) to 20/50 or Worse Characteristics II 
Refer regqry_2020_08 
SAC [2] 
3.1282
1 
Full Safety 
Programming 
note 
Percentage of Subjects with Blurred Vision/Dry Eye Event 
Associated with Worsening in Best Corrected Visual Acuity 
(BCVA) to 20/50 or Worse 
Refer regqry_2020_08 
SAC [2] 
3.1282
3 
Full Safety 
Programming 
note 
Percentage of Subjects with Ocular Symptoms (CTCAE) 
Associated with Worsening in Best Corrected Visual Acuity 
(BCVA) to 20/50 or Worse 
Refer regqry_2020_08 
SAC [2] 
3.1283
1 
Full Safety 
Programming 
note 
Summary of Unilateral Worsening in Best Corrected Visual 
Acuity (BCVA) to 20/200 or Worse Characteristics II 
Refer regqry_2020_08 
SAC [2] 
3.1284
1 
Full Safety 
Programming 
note 
Summary of Bilateral Worsening in Best Corrected Visual 
Acuity (BCVA) to 20/200 or Worse Characteristics II 
Refer regqry_2020_08 
SAC [2] 


 
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Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.1285
1 
Full Safety 
Programming 
note 
Update of Resolution Status for Unresolved Corneal Exam 
Finding 
Refer regqry_2020_08 
SAC [2] 
3.1285
2 
Full Safety 
Programming 
note 
Update of Resolution Status for Unresolved Corneal Exam 
Finding Patients with Interview Clinical data 
Refer present_2020_04 
SAC [2] 
3.1286
1 
Full Safety 
Programming 
note 
Update of Resolution Status for Unresolved Worsening in 
Best Corrected Visual Acuity (BCVA) Score (logMAR 
Score) 
Refer regqry_2020_08 
SAC [2] 
3.1287
1 
Full Safety 
Programming 
note 
Update of Resolution Status for Unresolved Blurred Vision 
and Dry Eye Events in Subjects with Keratopathy 
Refer regqry_2020_08 
SAC [2] 
3.1287
3 
Full Safety 
Programming 
note 
Update of Resolution Status for Unresolved Ocular 
Symptoms (CTCAE) in Subjects with Keratopathy 
Refer regqry_2020_08 
SAC [2] 
3.1288
1 
Full Safety 
Programming 
note 
Summary of Worst Post-baseline Change in Best Corrected 
Visual Acuity (BCVA) 
Refer regqry_2020_08 
SAC [2] 
3.1289
1 
Full Safety 
Programming 
note 
Summary of Worsening in Best Corrected Visual Acuity 
(BCVA) Score (logMAR Score >=0.12) Characteristics II 
Refer regqry_2020_08 
SAC [2] 
3.1292
1 
Full Safety 
Programming 
note 
Update of Resolution Status for Unresolved Worsening in 
Best Corrected Visual Acuity (BCVA) Score (logMAR Score 
>=0.12) 
Refer regqry_2020_08 
SAC [2] 
3.1293
1 
Full Safety 
Programming 
note 
Summary of Vision Blurred by Preferred term and Best 
Response Based on Independent Review Committee 
Refer regqry_2020_08 
SAC [2] 


 
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IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.1294
1 
Full Safety 
Programming 
note 
Summary of Dry Eye by Preferred term and Best Response 
Based on Independent Review Committee 
Refer regqry_2020_08 
SAC [2] 
3.1295
1 
Full Safety 
Programming 
note 
Summary of Vision Blurred by Maximum Grade, and Best 
Response Based on Independent Review Committee 
Refer regqry_2020_08 
SAC [2] 
3.1296
1 
Full Safety 
Programming 
note 
Summary of Dry Eye by Maximum Grade, and Best 
Response Based on Independent Review Committee 
Refer regqry_2020_08 
SAC [2] 
3.1297
1 
Full Safety 
Programming 
note 
Summary of Best Corrected Visual Acuity (BCVA) Score 
(Snellen Score) at Baseline Compared to 20/50 
Refer regqry_2020_08 
SAC [2] 
3.1298
1 
Full Safety 
Programming 
note 
Worsening in Best Corrected Visual Acuity (BCVA) Score 
(logMAR Score) Excluding Subjects with Follow-up Shorter 
Than 80 Days 
Refer regqry_2020_08 
SAC [2] 
3.1300 
Full Safety 
Mock-up 
SAFE_T11a 
Summary of Neutropenia and Infection Event 
 
SAC [1],SAC [2] 
3.5001
3 
Full Safety 
Programming 
note 
Summary of Worst-case Post baseline shift from baseline 
by BCVA categories 
Refer regqry_2021_01 
SAC [2] 
3.5002
0 
Full Safety 
Programming 
note 
Summary of Worst-case Post Baseline Change from 
Baseline in Best Corrected Visual Acuity (BCVA)Score 
(logMAR score) 
Refer regqry_2020_10 
SAC [2] 
3.5002
1 
Full Safety 
Programming 
note 
Summary of Worst-case Post Baseline Change from 
Baseline in Best Corrected Visual Acuity (BCVA)Score 
(logMAR score) in Subjects with Worsening to 20/50 or 
Worse in the Better Eye 
Refer regqry_2020_10 
SAC [2] 


 
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IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.5002
2 
Full Safety 
Programming 
note 
Summary of Worst-case Post Baseline Change from 
Baseline in Best Corrected Visual Acuity (BCVA)Score 
(logMAR score) in Subjects with Worsening to 20/50 or 
Worse in at Least One Eye but not the Better Eye 
Refer regqry_2020_10 
SAC [2] 
8.5007
0 
Full Safety 
Programming 
note 
Summary of Characteristics II for the Event of Giving up 
Driving due to Eyesight 
Refer regqry_2020_10 
SAC [2] 
8.5008
0 
Full Safety 
Programming 
note 
Summary of Characteristics II for the Event of Giving up 
Reading due to Eyesight 
Refer regqry_2020_10 
SAC [2] 
3.6010
0 
Full Safety 
Programming 
note 
Summary of Characteristics II for Keratopathy 
Refer regqry_2020_10 
SAC [2] 
3.7001
0 
Full Safety 
Programming 
note 
Summary of Dose Modifications for Subjects with 
Keratopathy 
Refer regqry_2020_22 
SAC [2] 
3.7001
2 
Full Safety 
Programming 
note 
Summary of Maximum Grade for Corneal Events (GSK 
scale) 
Refer regqry_2020_10 
SAC [2] 
3.9001
0 
Full Safety 
Programming 
note 
Summary of Time from Onset of Last Occurence to Last 
Exam in Subjects Who Did Not Recover from Grade 2 or 
Higher Corneal Exam Finding (GSK Scale) When Follow 
Up Ended 
Refer regqry_2020_22 
SAC [2] 
3.9002
0 
Full Safety 
Programming 
note 
Summary of Ocular Symptoms by Preferred Term and 
Maximum Grade in Subjects with Worst Grade of Corneal 
Exam Findings (GSK scale) =1 
Refer regqry_2020_22 
SAC [2] 


 
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IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.9004
0 
Full Safety 
Programming 
note 
Summary of Duration of Exposure since Re-start after First 
Dose Delay Due to Eye Disorder Events (CTCAE) 
Refer regqry_2020_22 
SAC [2] 
3.9005
0 
Full Safety 
Programming 
note 
Summary of Corneal Events (GSK Scale) Occurrences 
After Dose Reduction to 1.92 mg/kg 
Refer regqry_2020_22 
SAC [2] 
Death 
3.0450 
Full Safety 
DTH1a 
Summary of Deaths 
 
IA [1], Headline, 
SAC [1] , SAC 
[2] 
Laboratory: Chemistry  
3.0460 
Full Safety 
LB1 
Summary of Chemistry Changes from Baseline  
ICH E3. Include the lab test ‘Albumin 
Creatinine Ratio’ 
SAC [1] 
3.0470 
Full Safety 
OLB11B 
Summary of Worst Case Chemistry Changes from Baseline 
with Respect to the Normal Range  
ICH E3 
SAC [1] 
3.0480 
Full Safety 
OLB9B 
Summary of Worst Case Chemistry Grade Changes from 
Baseline Grade 
 
IA [1], Headline, 
SAC [1] 
3.1220 
Full Safety 
Programming 
note 
Summary of Study Day and Number of Doses at the Onset 
of First Occurrence of AST Value >= 3 ULN  
See similar post-hoc output in 
BMA117159 (primary_01) 
SAC [1] 
3.1230 
Full Safety 
Programming 
note 
Summary of Study Day and Number of Doses at the Onset 
of First Occurrence of LDH Value >= 3 ULN 
See similar post-hoc output in 
BMA117159 (primary_01) 
SAC [1] 
3.1240 
Full Safety 
Programming 
note 
Summary of Study Day and Number of Doses at the Onset 
of First Occurrence of CPK Value >= 3 ULN 
See similar post-hoc output in 
BMA117159 (primary_01) 
SAC [1] 
3.1250 
Full Safety 
Programming 
note 
Summary of Duration from Onset of First Occurrence of 
AST Value >= 3 ULN to Grade 0 or 1 
See similar post-hoc output in 
BMA117159 (primary_01)  
SAC [1] 


 
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IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.1260 
Full Safety 
Programming 
note 
Summary of Duration from Onset of First Occurrence of 
CPK Value >= 3 ULN to Grade 0 or 1 
See similar post-hoc output in 
BMA117159 (primary_01)  
SAC [1] 
3.1270 
Full Safety 
Programming 
note 
Summary of Duration from Onset of First Occurrence of 
LDH Value >= 3 ULN to Grade 0 or 1 
See similar post-hoc output in 
BMA117159 (primary_01)  
SAC [1] 
3.1310 
Full Safety 
Mock-up 
Safe_T13 
Shift in Albumin Creatinine Ratio (mg/g) from Baseline to 
Worst Post-Baseline 
 
SAC [1] 
Laboratory: Haematology 
3.0490 
Full Safety 
LB1 
Summary of Haematology Changes from Baseline 
ICH E3 
SAC [1] 
3.0500 
Full Safety 
OLB11B 
Summary of Worst Case Haematology Changes from 
Baseline with Respect to the Normal Range 
ICH E3 
SAC [1] 
3.0510 
Full Safety 
OLB9B 
Summary of Worst Case Hematology Grade Changes from 
Baseline Grade 
 
IA [1], Headline, 
SAC [1] 
Laboratory: Urinalysis 
3.0520 
 Full 
Safety 
LB1 
Summary of Urine Concentration Changes from Baseline 
ICH E3 
SAC [1] 
3.0530 
Full Safety 
UR1 
Summary of Worst Case Urinalysis Results (Discrete or 
Character Values) Post-Baseline Relative to Baseline 
ICH E3 
SAC [1] 
Laboratory: Hepatobiliary (Liver) 
3.0540 
 Full 
Safety 
LIVER1 
Summary of Liver Monitoring/Stopping Event Reporting 
IDSL 
SAC [1] 
3.0550 
 Full 
Safety 
LIVER10 
Summary of Hepatobiliary Laboratory Abnormalities 
IDSL 
SAC [1] 
ECG 
3.0590 
Full Safety 
EG1 
Summary of ECG Findings per Investigator Assessment 
IDSL 
SAC [1] 


 
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IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.0600 
Full Safety 
OECG1B 
Summary of Worst-case Increases in Fridericia's QTc 
Includes all ECG values (both baseline 
and post-baseline) regardless of 
whether they are calculated based on 
triplicate/duplicate/single measurement.  
SAC [1] 
3.0610 
Full Safety 
OECG2B 
Summary of Worst-case Amount of Increase from Baseline 
Value in Fridericia's QTc 
Includes all ECG values (both baseline 
and post-baseline) regardless of 
whether they are calculated based on 
triplicate/duplicate/single measurement. 
SAC [1] 
3.0620 
Full Safety 
EG2 
Summary of Change from Baseline in ECG Values by Visit 
IDSL Includes all ECG values (both 
baseline and post-baseline) regardless 
of whether they are calculated based 
on triplicate/duplicate/single 
measurement. 
SAC [1] 
Vital Signs 
3.0630 
Full Safety 
VS1 
Summary of Change from Baseline in Vital Signs 
ICH E3 
SAC [1] 
3.0640 
Full Safety 
OVT1B 
Summary of Worst Case Changes in Heart Rate from 
Baseline 
 
SAC [1] 
3.0650 
Full Safety 
OVT2B 
Summary of Worst Case Increases in Systolic Blood 
Pressure from Baseline 
 
SAC [1] 
3.0660 
Full Safety 
OVT2B 
Summary of Worst Case Increases in Diastolic Blood 
Pressure from Baseline 
 
SAC [1] 
3.0670 
Full Safety 
OVT1B 
Summary of Worst Case Changes in Temperature from 
Baseline 
 
SAC [1] 
ECOG Performance Status 
3.0680 
Full Safety 
PS1A 
Summary of ECOG Performance Status 
 
SAC [1] 
3.0690 
Full Safety 
PS3A 
Summary of Change in ECOG Performance Status from 
Baseline 
 
SAC [1] 
ECHO 
3.0700 
Full Safety 
OLVEF1A 
Summary of Worst Left Ventricular Ejection Fraction 
Change from Baseline 
 
SAC [1] 


 
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IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Anti-Drug Antibody 
3.0710 
Full Safety 
Programming 
note 
Summary of Human Anti-GSK2857916 Antibodies (ADA) 
Over Time 
See Table 3.0841 from BMA117159 
(primary_01) with following changes: 
1.Under each visit, add another 
category:  
'Neutralizing Antibody Results' 
      n 
      POSITIVE 
      NEGATIVE 
2. Replace ‘Negative, Conclusive’ and 
‘Negative, Inconclusive’ rows with 
‘Negative’ 
3. Add to note: Only samples with 
confirmed positive ADA results were 
tested in the Neutralizing Antibody 
Assay. 
SAC [1],SAC [2] 


 
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IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.0720 
Full Safety 
Programming 
note 
Summary of Human Anti-GSK2857916 Antibodies (ADA) 
See Table 3.0851 from BMA117159 
(primary_01) with following changes. 
1. Under section for baseline ADA 
results, add following two categories: 
.     a "Number of subjects with 
confirmed positive ADA result that are 
positive for Neutralizing Antibodies" 
     b. "Number of subjects with 
confirmed positive ADA result that are 
negative for Neutralizing Antibodies" 
2. Under section for post-baseline ADA 
results, add following two categories: 
     a "Number of subjects with at least 
one confirmed positive ADA result that 
are positive for Neutralizing Antibodies"  
 
     b. "Number of subjects with at least 
one confirmed positive ADA result that 
are negative for Neutralizing 
Antibodies"  
3.In the table, replace two cases of 
‘<=25000 ng/mL’ with ‘<=500000 
ng/mL’. 
4. Add to note: Only samples with 
confirmed positive ADA results were 
tested in the Neutralizing Antibody 
Assay. 
SAC [1],SAC [2] 


 
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IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Ocular findings for General study (Baseline to Last follow-up) 
3.0730 
Full Safety 
Programming 
note  
Summary of Best Corrected Visual Acuity Test (BCVA) 
Scores (logMAR score) 
Use Table 3.0501 from BMA117159 
(primary_01) study as template. 
Following “worst change from baseline’, 
add summary for ‘Most frequent change 
from baseline’, and pick the worst 
category if there is tie.  Under column 
‘Eye’, in addition to Right/Left add 
‘Worse’ (worse of two eye) and ‘Better’ 
(better of two eye). Definition of 3 
categories of change are same as in 
BMA117159 (primary_01). 
SAC [1] ,SAC 
[2] 
3.0732 
Full Safety 
Programming 
note  
Summary of Best Corrected Visual Acuity Test (BCVA) 
Scores (logMAR score) due to Corneal Finding (GSK 
Scale) 
Use Table 3.0501 from BMA117159 
(primary_01) study as template. 
Following “worst change from baseline’, 
add summary for ‘Most frequent change 
from baseline’, and pick the worst 
category if there is tie.  Under column 
‘Eye’, in addition to Right/Left add 
‘Worse’ (worse of two eye) and ‘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 
finding flag=’Y’. 
SAC [1] ,SAC 
[2] 
3.0740 
Full Safety 
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  
Eye (R/L) and subject (either eye) 
SAC [1] ,SAC 
[2] 
3.0760 
Full Safety 
Mock-up 
SAFE_T8 
Number (%) of Subjects with Intraocular Pressure (IOP) >= 
22mm Hg Anytime Post-Baseline  
 
SAC [1] 


 
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Title  
Programming Notes 
Deliverable 
[Priority] 
3.0770 
Full Safety 
Mock-up 
SAFE_T8a 
Number (%) of Subjects Who Start Treatment for 
Intraocular Pressure (IOP) after First dose of GSK2857916  
 
SAC [1] 
3.0780 
Full Safety 
Mock-up 
SAFE_T9 
Shift in Pupillary Exam Findings from Baseline to Worst 
Post-Baseline 
By subject (worse eye). See Section 
8.5 Ocular findings from ophthalmic 
exam for details. 
SAC [1] 
3.0790 
Full Safety 
Mock-up 
SAFE_T9 
Shift in Extraocular Muscle Movement from Baseline to 
Worst Post-Baseline 
By eye (R/L) and subject (worse eye). 
See Section 8.5 Ocular findings from 
ophthalmic exam for details. 
SAC [1] 
3.0800 
Full Safety 
Mock-up 
SAFE_T9 
Shift in Ptosis from Baseline to Worst Post-Baseline 
By eye (R/L) and subject (worse eye). 
See Section 8.5 Ocular findings from 
ophthalmic exam for details. 
SAC [1] 
3.0810 
Full Safety 
Mock-up 
SAFE_T9 
Shift in Blepharitis/MGD from Baseline to Worst Post-
Baseline 
By eye (R/L) and subject (worse eye). 
See Section 8.5 Ocular findings from 
ophthalmic exam for details. 
SAC [1] 
3.0820 
Full Safety 
Mock-up 
SAFE_T9 
Shift in Conjunctival Exam Findings from Baseline to Worst 
Post-Baseline 
By eye (R/L) and subject (worse eye). 
Create shift table for each of 3 findings: 
Chemosis (Absent/Present); Bulbar 
Conjunctiva White and Quiet: (Yes/No); 
Palpebral Conjunctiva within normal 
limits (Yes/No);See Section 8.5 Ocular 
findings from ophthalmic exam for 
details. 
SAC [1] 
3.0840 
Full Safety 
Mock-up 
SAFE_T9 
Shift in Scleritis from Baseline to Worst Post-Baseline 
By eye (R/L) and subject (both eyes in 
same ocular exam). See Section 8.5 
Ocular findings from ophthalmic exam 
for details. 
SAC [1] 
3.0852 
Full Safety 
Mock-up 
SAFE_T9 
Shift in Corneal Epithelium Findings from Baseline to Worst 
Post-Baseline 
By eye (R/L) and subject (worse eye). 
See Section 8.5 Ocular findings from 
ophthalmic exam for details.  
SAC [1] ,SAC 
[2] 


 
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Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.0851 
Full Safety Mock-up 
SAFE_T9 
Shift in Corneal Epithelium Findings from Baseline to Worst 
Post-Baseline for Microcysts without Edema 
 
SAC [1],SAC [2] 
3.0850 
Full Safety Mock-up 
SAFE_T9 
Shift in Corneal Epithelium Findings from Baseline to Worst 
Post-Baseline for Corneal Epithelium and Corneal Stroma 
 
SAC [1],SAC [2] 
3.0860 
Full Safety 
Mock-up 
SAFE_T14 
Summary of Findings for Punctate Keratopathy 
By eye (R/L) and subject (worse eye). 
See Section 8.5 Ocular findings from 
ophthalmic exam for details.  
SAC [1],SAC [2] 
3.0930 
Full Safety 
Mock-up 
SAFE_T9 
Shift in Corneal Endothelium Findings from Baseline to 
Worst Post-Baseline 
By eye (R/L) and subject (worse eye). 
See Section 8.5 Ocular findings from 
ophthalmic exam for details. 
SAC [1] 
3.0940 
Full Safety 
Mock-up 
SAFE_T12 
Summary of Presence of Descemet's Folds/ Endothelial 
Lesion at Any Time Post-Baseline  
By eye (R/L) and subject (either eye).  
See Section 8.5 Ocular findings from 
ophthalmic exam for details. 
SAC [1] 
3.0970 
Safety 
Mock-up 
SAFE_T10 
Summary for Change from Baseline in Pachymetry 
See Section 8.5 Ocular findings from 
ophthalmic exam for details. 
Pachymetry: decrease in value means 
improvement; 
SAC [1] 
3.0980 
Full Safety 
Mock-up 
SAFE_T7 
Summary for Change from Baseline to Worst Post-Baseline 
in Schirmer's Test and Tear Break-up Time 
See Section 8.5 Ocular findings from 
ophthalmic exam for details. Tear 
break-up time/Schirmer’s test: increase 
in value means improvement., 
SAC [1] ,SAC 
[2] 
3.1340 
Full Safety Mock-up 
SAFE_T9a 
Shift in Schirmer's Test from Baseline to Worst Post-
Baseline  
See Section 8.5 Ocular findings from 
ophthalmic exam for details 
SAC [1] 
3.1350 
Full Safety Mock-up 
SAFE_T9a 
Shift in Tear Break-up Time from Baseline to Worst Post-
Baseline  
See Section 8.5 Ocular findings from 
ophthalmic exam for details 
SAC [1] 
3.1000 
Full Safety 
 Mock-up 
SAFE_T9 
Shift in Slit Lamp Exam Findings from Baseline to Worst 
Post-Baseline 
By eye (R/L) and subject (worse eye). 
See Section 8.5 Ocular findings from 
ophthalmic exam for details. 
SAC [1] ,SAC 
[2] 


 
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IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.1010 
Full Safety 
Mock-up 
SAFE_T12 
Summary of Presence of Iris Findings at Any Time Post-
Baseline 
By eye (R/L) and subject (either eye). 
Summary tables for number (%) of eyes 
with 'Transillumination defect', 
'Nodules', or 'Neovascularization' at any 
post-baseline ocular exam. See 
Section 8.5 Ocular findings from 
ophthalmic exam for details. 
SAC [1] ,SAC 
[2] 
3.1020 
Full Safety 
Mock-up 
SAFE_T9 
Shift in Pseudophakia and Cataracts from Baseline to 
Worst Post-Baseline 
By eye (R/L) and subject (worse eye). 
See Section 8.5 Ocular findings from 
ophthalmic exam for details. 
SAC [1] 
3.1040 
Full Safety Mock-up 
SAFE_T8 
Number of Subjects (%) Underwent Surgery due to 
Cataract Post-Baseline  
 
SAC [1] 
3.1050 
Full Safety 
Mock-up 
SAFE_T9 
Shift in Findings from FUNDUS Photograph from Baseline 
to Worst Post-Baseline 
By eye (R/L) and subject (worse eye). 
See Section 8.5 Ocular findings from 
ophthalmic exam for details. 
SAC [1] 
Ocular findings for General study from EOT to last follow-up visit 
3.1060 
Full Safety 
Mock-up 
SAFE_T15 
Summary of Change (Worsening, No Change, 
Improvement) in Best Corrected Visual Acuity (BCVA) from 
EOT Visit to Last Follow-Up Visit 
By eye (R/L) and subject (worse eye). 
SAC [1] ,SAC 
[2] 
3.1070 
Full Safety 
Mock-up 
SAFE_T15 
Summary of Change (Worsening, No Change, 
Improvement) in Intraocular Pressure (IOP) from EOT Visit 
to Last Follow-Up Visit 
By eye (R/L) and subject (worse eye). 
For IOP, decrease in value means 
improvement. 
SAC [1] 
3.1080 
Full Safety 
Mock-up 
SAFE_T15 
Summary of Change (Worsening, No Change, 
Improvement) in Corneal Epithelium Findings from EOT 
Visit to Last Follow-Up Visit 
By eye (R/L) and subject (worse eye). 
See Section 8.5 Ocular findings from 
ophthalmic exam for details 
SAC [1] ,SAC 
[2] 
3.1090 
Full Safety 
Mock-up 
SAFE_T15 
Summary of Change (Worsening, No Change, 
Improvement) in Corneal Endothelium Findings from EOT 
Visit to Last Follow-Up Visit 
By eye (R/L) and subject (worse eye). 
See Section 8.5 Ocular findings from 
ophthalmic exam for details 
SAC [1] ,SAC 
[2] 


 
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IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.1100 
Full Safety 
Mock-up 
SAFE_T15 
Summary of Change (Worsening, No Change, 
Improvement) in Pachymetry, Tear break up time, and 
Schirmer’s test from EOT Visit to Last Follow-Up Visit 
By eye (R/L) and subject (worse eye). 
Pachymetry: decrease in value means 
improvement; Tear break-up 
time/Schirmer’s test: increase in value 
means improvement., 
SAC [1] 
3.1110 
Full Safety Mock-up 
SAFE_T4 
Summary of Resolution Time from EOT Visit in Best 
Corrected Visual Acuity (BCVA) 
By eye (R/L) and subject (worse eye). 
SAC [1] ,SAC 
[2] 
3.1120 
Full Safety Mock-up 
SAFE_T4 
Summary of Resolution Time from EOT Visit in Intraocular 
Pressure (IOP) 
By eye (R/L) and subject (worse eye). 
SAC [1] 
3.1130 
Full Safety 
Mock-up 
SAFE_T4 
Summary of Resolution Time from EOT Visit in Corneal 
Epithelium Findings 
By eye (R/L) and subject (worse eye). 
See Section 8.5 Ocular findings from 
ophthalmic exam for details 
SAC [1] ,SAC 
[2] 
3.1140 
Full Safety 
Mock-up 
SAFE_T4 
Summary of Resolution Time from EOT Visit in Corneal 
Endothelium Findings 
By eye (R/L) and subject (worse eye). 
See Section 8.5 Ocular findings from 
ophthalmic exam for details 
SAC [1] ,SAC 
[2] 
3.1150 
Full Safety Mock-up 
SAFE_T4 
Summary of Resolution Time from EOT Visit in 
Pachymetry, Tear break up time, and Schirmer’s test 
By eye (R/L) and subject (worse eye). 
SAC [1] 
Ocular sub-study (Cycle 1- 4) 
3.1160 
Ocular 
Sub-Study  
Mock-up 
SAFE_T16 
Summary of Worst Grade of Corneal Events (GSK Scale) 
during Cycle 1-4 by Randomized Topical Corticosteroids 
Treatment 
 
SAC [1] 
3.1170 
Ocular 
Sub-Study  
Mock-up 
SAFE_T17 
Summary of Best Corrected Visual Acuity (BCVA) Scores 
(logMAR score) by Randomized Topical Corticosteroids 
Treatment 
 
SAC [1] 
3.1180 
Ocular 
Sub-Study  
Mock-up 
SAFE_T18 
Summary of Onset Time to First Drug-Related Corneal 
Event (GSK Scale) by Randomized Topical Corticosteroids 
Treatment 
 
SAC [1] 


 
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126 
Safety: Tables 
No. 
Populatio
n 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
3.1190 
Ocular 
Sub-Study  
Mock-up 
SAFE_T19 
Summary of Onset Time to Initiation of Topical 
Corticosteroids Treatment in Eyes Not-Randomized to 
Topical Corticosteroids Treatment 
 
Headline, SAC 
[1] 
3.1200 
Ocular 
Sub-Study  
Mock-up 
SAFE_T20 
Shift in Corneal findings (per Ocular Exam) from Baseline to 
Worst during Cycle 1-4 by Randomized Topical 
Corticosteroids Treatment 
 
SAC [1] 


 
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15.13.9. 
Safety Figures 
Safety: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Laboratory 
3.0020 
Full Safety 
LIVER14 
Scatter Plot of Maximum vs. Baseline for ALT 
IDSL 
SAC [1] 
3.0040 
Full Safety 
LIVER9 
Scatter Plot of Maximum Bilirubin versus Maximum 
ALT – eDISH Plot 
IDSL 
SAC [1] 
3.0050 
Full Safety 
LIVER9 
Scatter Plot of Maximum AST vs Maximum LDH - 
eDISH Plot 
IDSL 
SAC [1] 
3.0060 
Full Safety 
LIVER9 
Scatter Plot of Maximum AST vs Maximum 
Creatinine Kinase - eDISH Plot  
IDSL 
SAC [1] 
3.0070 
Full Safety 
LIVER9 
Scatter Plot of Maximum LDH vs Maximum 
Creatinine Kinase - eDISH Plot  
IDSL 
SAC [1] 
3.0080 
Full Safety 
LIVER9 
Scatter Plot of Maximum Albumin/Creatinine Ratio (> 
2000 mg/g) vs. Concomitant Values of Serum 
Creatinine 
Concomitant window =  7 days 
SAC [1] 
3.0090 
Full Safety  
EG8 
Box Plot of Values for Selected Lab Tests by Visit 
Selected lab tests are: haemoglobin, platelets, 
neutrophils, serum creatinine, and albumin/creatinine 
ratio. 
SAC [1] 
Profile Plot 
3.0030 
Evaluable 
Programming 
note 
Profile Plot for Subjects (Evaluable)  
See Figure 3.0030 created at IA for 205678 
IA [1] 
3.0031 
Full Safety 
Programming 
note 
Profile Plot for Subjects  
See Figure 12.0150 from BMA117159 
(primary_01) 
SAC [1] 


 
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128 
Safety: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
ECG 
3.0100 
Full Safety 
OECG4 
Fridericia's QTc Shifts from Baseline to Worst-case 
Post Baseline 
 
SAC [1] 


 
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Safety: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Corneal events 
3.10031 
Full Safety 
Programming 
note 
Plot of Visual Acuity and Corneal Finding Grade for 
Subjects Experiencing >1 Corneal Event (GSK 
Scale), Initial Dose Level = 2.5 mg/kg 
Refer present_2020_04 
SAC [2] 
3.53010 
Full Safety 
Programming 
note 
Plot of Time to Recovery Post Treatment 
Discontinuation for Corneal Exam Findings 
Refer regqry_2020_10 
SAC [2] 
3.53020 
Full Safety 
Programming 
note 
Plot of Time to Recovery Post Treatment 
Discontinuation for Keratopathy 
 Refer regqry_2020_10 
SAC [2] 
3.50030 
Full Safety 
Programming 
note 
Bar Chart of Grade of Corneal Exam Finding by 
Cycle 
Refer regqry_2020_10 
SAC [2] 
 


 
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15.13.10. Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Concentration 
4.0010 
Full PK 
PK01 
Summary of Plasma GSK2857916 (ADC) PK Concentration-
Time Data  
By dose level 
SAC [1], SAC 
[2] 
4.0020 
Full PK 
PK01 
Summary of Plasma GSK2857916 (Total Antibody) PK 
Concentration-Time Data 
By dose level 
SAC [1] ,SAC 
[2] 
4.0030 
Full PK 
PK01 
Summary of Plasma cys-mcMMAF PK Concentration-Time 
Data 
 By dose level 
SAC [1] ,SAC 
[2] 
PK Parameter 
4.0040 
Full PK 
PK06 
Summary of Derived GSK2857916 (ADC) PK Parameters 
PK06 with both transformed and 
untransformed values.  
SAC [1] 
4.0041 
Full PK 
PK13 
Listing of Derived GSK2857916 (ADC) PK Parameters 
(Untransformed) 
  
SAC [1] 
4.0050 
Full PK 
PK06 
Summary of Derived GSK2857916 (Total Antibody) PK 
Parameters 
PK06 with both transformed and 
untransformed values.  
SAC [1] 
4.0051 
Full PK 
PK13 
Listing of Derived GSK2857916 (Total Antibody) PK 
Parameters (Untransformed) 
 
SAC [1] 
4.0060 
Full PK 
PK06 
Summary of Derived cys-mcMMAF PK Parameter 
PK06 with both transformed and 
untransformed values. 
SAC [1] 
4.0061 
Full PK 
PK13 
Listing of Derived cys-mcMMAF PK Parameters 
(Untransformed) 
 
SAC [1] 
Accumulation Ratio 
4.0070 
Full PK 
PK05 
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (ADC) 
Include Ro(AUC) and Ro(Cmax) with 
95%CI in one table.  
SAC [1] 


 
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Pharmacokinetic: Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.0080 
Full PK 
PK05 
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Total Antibody) 
Include Ro(AUC) and Ro(Cmax) with 
95%CI in one table.  
SAC [1] 
4.0090 
Full PK 
PK05 
Summary of Results of Accumulation Ratio Assessment for 
cys-mcMMAF 
Include Ro(AUC) and Ro(Cmax) with 
95%CI in one table.  
SAC [1] 
 


 
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15.13.11. Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Concentration 
4.0010 
Full PK 
PK16 
Individual Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log)  
 
SAC [1], SAC 
[2] 
4.0020 
Full PK 
PK16 
Individual Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log)  
 
SAC [1] , SAC 
[2] 
4.0030 
Full PK 
PK16 
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) 
 
SAC [1] , SAC 
[2] 
4.0040 
Full PK 
PK17 
Mean Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) 
 
SAC [1] , SAC 
[2] 
4.0050 
Full PK 
PK17 
Mean Plasma GSK2857916 (Total Anti-body) Concentration-
Time Plots (Linear and Semi-Log)  
 
SAC [1] , SAC 
[2] 
4.0060 
Full PK 
PK17 
Mean Plasma GSK2857916 (ADC and Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log)  
See similar Figure 14.0190 from 
BMA117159 (primary_01) 
SAC [1] , SAC 
[2] 
4.0070 
Full PK 
PK17 
Mean Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log)  
 
SAC [1] , SAC 
[2] 
4.0080 
Full PK 
PK18 
Median Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) 
 
SAC [1] 
4.0090 
Full PK 
PK18 
Median Plasma GSK2857916 (Total Anti-body) Concentration-
Time Plots (Linear and Semi-Log)  
 
SAC [1] 
4.0100 
Full PK 
PK18 
Median Plasma GSK2857916 (ADC and Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log)  
See similar Figure 14.0200 from 
BMA117159 (primary_01) 
SAC [1] 


 
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Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
4.0110 
Full PK 
PK18 
Median Plasma GSK2857916 (cys-mcMMAF) Concentration-
Time Plots (Linear and Semi-Log)  
 
SAC [1] 
Accumulation Ratio 
4.0120 
Full PK 
PK28 
Plot of Individual (+Geometric Mean and 95%CI) of 
Accumulation Ratios for GSK2857916 Analytes (Linear and 
Semi-Log)  
Plot accumulation ratios versus dose. 
Add a reference line at 1. Plot 
Ro(AUC)and Ro(Cmax) on different 
plots. Only include geometric mean 
and 95%CI. Plot analytes: ADC, total 
antibody, and cys-mcMMAF on the 
same plot. 
SAC [1] 
 
 


 
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15.13.12. Pharmacokinetic / Pharmacodynamic Figures 
Pharmacokinetic / Pharmacodynamic: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
[Insert Endpoint Category] 
7.0010 
Full PK 
PK_F2 
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (ADC) 
Includes only ECG values (both 
baseline and post-baseline) calculated 
based on triplicate/duplicate 
measurement. 
SAC [1] 
7.0020 
Full PK 
PK_F2 
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for GSK2857916 (Total Antibody)  
Includes only ECG values (both 
baseline and post-baseline) calculated 
based on triplicate/duplicate 
measurement. 
SAC [1] 
7.0030 
Full PK 
PK_F2 
Plot of Fridericia’s QTc Change from Baseline versus PK 
Concentration for cys-mcMMAF 
Includes only ECG values (both 
baseline and post-baseline) calculated 
based on triplicate/duplicate 
measurement. 
SAC [1] 
 
 
 
 
 


 
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15.13.13. Health Outcomes Tables 
Health Outcomes: Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
EORTC QLQ-C30 
8.0010 
Full 
Analysis 
Mock-up 
PRO_T1 
Summary of Change in EORTC QLQ-C30 Summary Score from 
Baseline  
Timepoints includes EOT visit 
SAC [1], SAC 
[2] 
8.0020 
Full 
Analysis 
Mock-up 
PRO_T1 
Summary of Change in EORTC QLQ-C30 Domain Scores from 
Baseline  
Including score for 15 domains. 
Timepoints includes EOT visit 
SAC [1] ,SAC 
[2] 
8.0030 
Full 
Analysis 
Mock-up 
PRO_T2 
Number (%) of Subjects with Improvement in EORTC QLQ-C30 
Summary Score >= 10 by Visit  
Timepoints includes EOT visit 
SAC [1] 
8.0040 
Full 
Analysis 
Mock-up 
PRO_T2 
Number (%) of Subjects with Improvement in EORTC QLQ-C30 
Domain Score >= 10 by Visit 
Including score for 15 domains. 
Timepoints includes EOT visit 
SAC [1] 
8.0050 
Full 
Analysis 
Mock-up 
PRO_T2 
Number (%) of Subjects with Improvement in EORTC QLQ-C30 
Summary Score >= 5 by Visit 
Timepoints includes EOT visit 
SAC [1] 
8.0060 
Full 
Analysis 
Mock-up 
PRO_T2 
Number (%) of Subjects with Improvement in EORTC QLQ-C30 
Domain Score >= 5 by Visit 
Including score for 15 domains. 
Timepoints includes EOT visit 
SAC [1] 
EORTC QLQ-MY20 
8.0070 
Full 
Analysis 
Mock-up 
PRO_T1 
Summary of Change in EORTC QLQ-MY20 Domain Scores 
from Baseline  
Timepoints includes EOT visit. 
Including score from 4 domains 
SAC [1], SAC 
[2] 
8.0080 
Full 
Analysis 
Mock-up 
PRO_T2 
Number (%) of Subjects with Improvement in EORTC QLQ-
MY20 Domain Scores >= 10 by Visit  
Pending on the availability of MID; 
Timepoints includes EOT visit 
Including score for 4 domains 
SAC [1] 
8.0081 
Full 
Analysis 
Mock-up 
PRO_T2 
Number (%) of Subjects with Improvement in EORTC QLQ-
MY20 Domain Scores >= 5 by Visit  
Pending on the availability of MID; 
Timepoints includes EOT visit 
Including score for 4 domains 
SAC [1] 


 
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Health Outcomes: Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
PRO-CTCAE 
8.0090 
Full Safety 
Mock-up 
PRO_T3 
Summary of Maximum Post-Baseline PRO-CTCAE Score  
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).  
SAC [1], SAC 
[2] 
NEI-VFQ-25 
8.0100 
Full Safety 
Mock-up 
PRO_T1 
Summary of Change in NEI-VFQ-25 Overall Composite Scores 
from Baseline  
Timepoints includes EOT visit, last 
follow-up visit, and worst change from 
baseline.  
SAC [1], SAC 
[2] 
8.0110 
Full Safety 
Mock-up 
PRO_T1 
Summary of Change in NEI-VFQ-25 Subscale Scores from 
Baseline  
11 subscale score.  
Timepoints includes EOT visit, last 
follow-up visit, and worst change from 
baseline. 
SAC [1], SAC 
[2] 
8.0120 
Full Safety 
Mock-up 
PRO_T4 
Summary of Worst Change from Baseline in NEI-VFQ-25 
Overall Composite Score by Worst Grade of Corneal Event 
(GSK Scale)  
 
SAC [1] 
OSDI 
8.0130 
Full Safety 
Mock-up 
PRO_T1 
Summary of Change in OSDI Total Scores from Baseline  
Timepoints includes EOT visit, last 
follow-up visit, and worst change from 
baseline. 
SAC [1], SAC 
[2] 
8.0140 
Full Safety 
Mock-up 
PRO_T1 
Summary of Change in OSDI Subscale Scores from Baseline  
Including 3 subscale scores.  
Timepoints includes EOT visit, last 
follow-up visit, and worst change from 
baseline. 
SAC [1] , SAC 
[2] 
8.0150 
Full Safety 
Mock-up 
PRO_T4 
Summary of Worst Change from Baseline in OSDI Total Scores 
by Worst Grade of Corneal Event (GSK Scale)  
 
SAC [1] 


 
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15.13.14. Health Outcomes Figures 
Health Outcomes: Figures 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable 
[Priority] 
PRO-CTCAE 
8.0010 
Full Safety 
Mock-up 
PRO_F1 
Stacked Bar Chart of PRO-CTCAE Score by Attributes and Visit  
For each selected item from PRO-
CTCAE library: create 3 sets of 
stacked bar charts (one for each of two 
dose arms) for PRO-CTCAE score for 
each of 3 attributes (frequency, 
severity and/or interference).  
SAC [1], SAC 
[2] 
 
 
 
 


 
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15.13.15. ICH Listings 
ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Subject Disposition 
1.0020 
Full Analysis 
ES2 
Listing of Reasons for Study Withdrawal 
ICH E3.  
SAC [1], SAC 
[2] 
1.0030 
Full Analysis 
SD2 
Listing of Reasons for Study Treatment Discontinuation 
ICH E3 
SAC [1] , 
SAC [2] 
1.0040 
Full Analysis 
CP_RA1 
Listing of Planned and Actual Treatments 
IDSL 
SAC [1] 
Protocol Deviations 
1.0050 
Full Analysis 
DV2 
Listing of Important Protocol Deviations  
ICH E3 
SAC [1] 
1.0060 
Full Analysis 
IE3 
Listing of Participants with Inclusion/Exclusion Criteria 
Deviations 
ICH E3 
SAC [1] 
Populations Analysed 
1.0070 
Enrolled 
SP3a 
Listing of Participants Excluded from Any Population 
ICH E3 
SAC [1] 
Demographic and Baseline Characteristics 
1.0080 
Full Analysis 
DM2 
Listing of Demographic Characteristics 
ICH E3 
SAC [1] 
Prior and Concomitant Medications 
1.0100 
Full Safety 
OCM1A 
Listing of Concomitant Medications 
IDSL 
SAC [1] 
Exposure and Treatment Compliance 
1.0110 
Full Safety 
OEX8A 
Listing of Exposure Data 
ICH E3 
SAC [1] , 
SAC [2] 
Adverse Events 
1.0170 
Full Safety 
OAE04 
Listing of All Adverse Events 
ICH E3 
SAC [1] 


 
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ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.0180 
Full Safety 
OAE03 
Listing of Subject Numbers for Individual Adverse Events 
ICH E3 
SAC [1] 
1.0190 
Full Safety 
AE2 
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text 
IDSL 
SAC [1] 
Serious and Other Significant Adverse Events 
1.0200 
Full Safety 
OAE04 
Listing of Fatal Serious Adverse Events 
ICH E3 
SAC [1], SAC 
[2] 
1.0210 
Full Safety 
OAE04 
Listing of Non-Fatal Serious Adverse Events 
ICH E3 
SAC [1], SAC 
[2] 
1.0220 
Full Safety 
AE14 
Listing of Reasons for Considering as a Serious Adverse 
Event 
ICH E3 
SAC [1] , 
SAC [2] 
1.0240 
Full Safety 
OAE04 
Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment 
 
SAC [1] , 
SAC [2] 
1.0290 
Full Safety 
OAE04 
Listing of Eye Disorder (CTCAE) 
List AE under Eye Disorder SOC 
SAC [1] , 
SAC [2] 
1.0300 
Ocular Sub-
Study  
OAE04 
Listing of Eye Disorder (CTCAE) in Ocular Sub-Study 
Subjects 
List AE under Eye Disorder SOC 
SAC [1] , 
SAC [2] 
1.0310 
Full Safety 
OAE04 
Listing of Thrombocytopenia 
 
SAC [1] , 
SAC [2] 
1.0320 
Full Safety 
OAE04 
Listing of Infusion Related Reactions 
 
SAC [1] , 
SAC [2] 
1.0380 
Full Safety 
OAE04 
Listing of Neutropenia 
 
SAC [1] , 
SAC [2] 
Hepatobiliary (Liver) 
1.0330 
Full Safety 
MH2 
Listing of Medical Conditions for Participants with Liver 
Stopping Events 
IDSL 
SAC [1] , 
SAC [2] 


 
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ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.0340 
Full Safety 
SU2 
Listing of Substance Use for Participants with Liver Stopping 
Events 
IDSL 
SAC [1] 
All Laboratory 
1.0350 
Full Safety 
OLB7 
Listing of All Laboratory Data for Participants with Any Value 
of Potential Clinical Importance 
ICH E3 
SAC [1] , 
SAC [2] 
1.0360 
Full Safety 
OLB13 
Listing of Laboratory Data with Character Results 
ICH E3 
SAC [1] 
1.0370 
Full Safety 
UR2A 
Listing of Urinalysis Data for Participants with Any Value of 
Potential Clinical Importance 
ICH E3 
SAC [1] 
ECOG Performance Status 
Response 
1.0390 
Full Analysis 
RE5 
Listing of Independent Review Committee-Assessed 
Responses 
Also include information of MRD. 
SAC [1] , 
SAC [2] 
1.0400 
Full Analysis 
RE5 
Listing of Investigator-Assessed Responses 
Also include information of MRD. 
SAC [1] 
1.0410 
Full Analysis 
TTE9 
Listing of Duration of Response based on Independent 
Review Committee-Assessed Responses 
 
SAC [1] , 
SAC [2] 
1.0420 
Full Analysis 
TTE9 
Listing of Duration of Response based on Investigator-
Assessed Responses 
 
SAC [1] 
1.0430 
Full Analysis 
TTE9 
Listing of Progression-Free Survival based on Independent 
Review Committee-Assessed Responses 
 
SAC [1] , 
SAC [2] 
1.0440 
Full Analysis 
TTE9 
Listing of Progression-Free Survival based on Investigator-
Assessed Response 
 
SAC [1] 
1.0450 
Full Analysis 
TTE9 
Listing of Time to Response based on Independent Review 
Committee-Assessed Responses 
 
SAC [1] , 
SAC [2] 
1.0460 
Full Analysis 
TTE9 
Listing of Time to Response based on Investigator-Assessed 
Responses 
 
SAC [1] 


 
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ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
1.0470 
Full Analysis 
TTE9 
Listing of Time to Best Response based on Independent 
Review Committee-Assessed Responses 
 
SAC [1] , 
SAC [2] 
1.0480 
Full Analysis 
TTE9 
Listing of Time to Best Response based on Investigator-
Assessed Responses 
 
SAC [1] 
1.0490 
Full Analysis 
TTE9 
Listing of Time to Progression based on Independent Review 
Committee-Assessed Responses 
 
SAC [1] , 
SAC [2] 
1.0500 
Full Analysis 
TTE9 
Listing of Time to Progression based on Investigator-
Assessed Responses 
 
SAC [1] 
1.0510 
Full Analysis 
TTE9 
Listing of Overall Survival 
 
SAC [1] , 
SAC [2] 
Death 
1.0520 
Full Safety 
DTH3 
Listing of Deaths 
 
SAC [1] 
Pharmacokinetics 
1.0530 
Full PK 
PK07 
Listing of Plasma GSK2857916 (ADC) Pharmacokinetic 
Concentration-Time Data 
 
SAC [1] , 
SAC [2] 
1.0540 
Full PK 
PK07 
Listing of Plasma GSK2857916 (Total Antibody) 
Pharmacokinetic Concentration-Time Data 
 
SAC [1] , 
SAC [2] 
1.0550 
Full PK 
PK07 
Listing of Plasma cys-mcMMAF Pharmacokinetic 
Concentration-Time Data 
 
SAC [1] , 
SAC [2] 
1.0560 
Full PK 
PK15 
Listing of GSK2857916 (ADC) AUC and Cmax Accumulation 
Ratio 
 
SAC [1] 
1.0570 
Full PK 
PK15 
Listing of GSK2857916 (Total Antibody) AUC and Cmax 
Accumulation Ratio 
 
SAC [1] 
1.0580 
Full PK 
PK15 
Listing of cys-mcMMAF AUC and Cmax Accumulation Ratio 
 
SAC [1] 
 


 
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15.13.16. Non-ICH Listings 
Non-ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Response  
30.0010 
Full Analysis 
RE12 
Listing of Investigator-Assessed Best Response for Interim 
Review by First Dose Date 
 
IA [1] 
Medical Conditions 
Concomitant Medications 
30.0020 
Full Safety 
OCM1A 
Listing of Prophylactic Medication for Infusion-Related 
Reactions 
 
SAC [1], SAC 
[2] 
30.0030 
Full Safety 
OCM1A 
Listing of Eye Medications 
 
SAC [1], SAC 
[2] 
Blood and Blood Supportive Care Products 
30.0040 
Full Analysis 
BP4 
Listing of Blood Products 
 
SAC [1] 
30.0050 
Full Analysis 
BP5 
Listing of Blood Supportive Care Products 
 
SAC [1] 
Substance Use 
Anti-Cancer Therapy, Radiotherapy and Surgical Procedures 
30.0060 
Full Analysis 
AC6 
Listing of Prior Anti-Cancer Therapy 
 
SAC [1] 
30.0070 
Full Analysis 
AC7 
Listing of Anti-Cancer Radiotherapy 
 
SAC [1] 
30.0080 
Full Analysis 
OSP3 
Listing of Prior/On Treatment Cancer and Non-Cancer Related 
Surgical Procedures 
 
SAC [1] 
30.0090 
Full Analysis 
FAC3 
Listing of Follow-Up Anti-Cancer Therapy 
 
SAC [1] 


 
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Non-ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Disease Characteristics 
30.0100 
Full Analysis 
DC4 
Listing of Disease Characteristics at Screening 
Include the genetic characteristics 
SAC [1] 
30.0110 
Full Analysis 
DC3 
Listing of Disease Characteristics at Initial Diagnosis 
 
SAC [1] 
Exposure 
30.0120 
Full Safety 
OEX9 
Summary Listing of Overall Exposure and Dose Modifications  
 
SAC [1], SAC 
[2] 
3.10010 
Full Safety 
Programmin
g note 
Listing of All Dose Delays due to Corneal Events (GSK scale) 
See regqry_2020_02, 3.10010 
SAC [2] 
3.10011 
Full Safety 
Programmin
g note 
Listing of Dose Delays and Associated Eye Disorder Events 
(CTCAE) 
See regqry_2020_02 , 3.10011 
SAC [2] 
Laboratory 
30.0130 
Full Safety 
OLB7 
Listing of Grade 3 and Grade 4 Laboratory Data  
 
SAC [1], SAC 
[2] 
30.0140 
Full Safety 
LIVER13 
Listing of Subjects Meeting Hepatobiliary Laboratory Criteria 
Post-Baseline 
 
SAC [1] 
30.0150 
Full Safety 
LIVER5 
Listing of Liver Monitoring/Stopping Event Reporting 
 
SAC [1] 
ECG 
30.0160 
Full Safety 
OECG5A 
Listing of Fridericia’s QTc Values of Potential Clinical 
Importance 
 
SAC [1] 
Vital Signs 
30.0170 
Full Safety 
OVT7A 
Listing of Vital Sign Values of Potential Clinical Importance 
 
SAC [1] 


 
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144 
Non-ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
Anti-Drug Antibody 
30.0180 
Full Safety 
Programmin
g note 
Listing of Human Anti-GSK2857916 Antibody Results 
See Listing 30.0620 from BMA117159 
(primary_01) with following change:  
1. Add a new column 
'Neutralizing Antibody Assay' 
 between TITER and ADC 
Concentration. The result will be 
either ‘POSITIVE’ or ‘NEGATIVE’. 
2.Add a note: Neutralizing Antibody 
Assay was only applied to confirmed 
ADA positive samples. 
SAC [1], SAC 
[2] 
Corneal Events (GSK Scale) 
30.0190 
Full Safety 
Mock up 
SAFE_L2 
Listing of Corneal Events (GSK Scale) 
List corneal findings by eye R/L and 
patient as well as action taken with 
study treatment.  
SAC [1], SAC 
[2] 
30.0191 
Full Safety 
Programmin
g note 
Listing of Resolution in Grade of Corneal Events (GSK Scale) 
for each Corneal Event in patients experiencing >1 event 
See 30.0192 in present_2020_04 
SAC [2] 
30.0200 
Ocular Sub-
Study  
Mock up 
SAFE_L2 
Listing of Corneal Events (GSK Scale) in Ocular Sub-Study 
Subjects 
List corneal findings by eye R/L and 
patient as well as action taken with 
study treatment.  
When break down by treatment arm, 
also included the information on which 
eye is randomized to corticosteroids 
(e. g Eye randomized to topical 
corticosteroids treatment = L.) 
SAC [1], SAC 
[2] 
8.0102 
Full Safety 
Programmin
g note 
Listing of BCVA for patients who gave up driving due to 
eyesight 
Refer present_2020_04 
SAC [2] 


 
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145 
Non-ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
8.0103 
Full Safety 
Programmin
g note 
Listing of BCVA for patients who experienced difficulty reading 
newspapers due to eyesight 
Refer present_2020_04 
SAC [2] 
Ocular Exam 
30.0210 
Full Safety 
Programmin
g note 
Listing of Visual Acuity and Abnormal Corneal Exam Results 
See Listing 30.0260 from BMA117159 
(primary_01) 
SAC [1] 
30.0220 
Full Safety 
Programmin
g note 
Listing of Abnormal Conjunctival Exam Results  
See Listing 30.0330 from BMA117159 
(primary_01) 
SAC [1] 
30.0230 
Full Safety 
Programmin
g note 
Listing of Abnormal Slit Lamp Anterior Chamber, Slit Lamp Iris, 
and Slit Lamp Lens Exam Results 
See Listing 30.0210 above 
SAC [1] 
30.0240 
Full Safety 
Programmin
g note 
Listing of Abnormal Dilated Fundoscopic Exam Results 
See Listing 30.0210 above 
SAC [1] 
Health Outcome 
30.0250 
Full Analysis 
VS4 
Listing of EORTC QLQ-C30 Scores 
use collected visit dates. List overall 
summary score and 14 domain scores 
SAC [1] 
30.0260 
Full Analysis 
VS4 
Listing of EORTC QLQ-MY20 Scores 
use collected visit dates. List 4 
domain scores 
SAC [1] 
30.0270 
Full Safety 
VS4 
Listing of PRO-CTCAE response 
use collected visit dates. List 
response for Frequency, Severity, 
Interference, and Present/Absence. 
SAC [1] 
30.0280 
Full Safety 
VS4 
Listing of NEI-VFQ-25 Scores 
use collected visit dates. List overall 
composite score and 11 sub-scores 
SAC [1] 
30.0290 
Full Safety 
VS4 
Listing of OSDI Scores 
use collected visit dates. List total 
score and 3 sub-scores. 
SAC [1] 


 
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146 
Non-ICH: Listings 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
[Priority] 
PK/PD 
30.0300 
Full PK 
Programmin
g Note 
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (ADC) Pharmacokinetic Concentration-Time 
Data 
See Listing 30.0690 in BMA117159 
(primary_01) 
SAC [1] 
30.0310 
Full PK 
Programmin
g Note 
Listing of Fridericia’s QTc Change from Baseline and 
GSK2857916 (Total Antibody) Pharmacokinetic Concentration-
Time Data 
See Listing 30.0700 in BMA117159 
(primary_01) 
SAC [1] 
30.0320 
Full PK 
Programmin
g Note 
Listing of Fridericia’s QTc Change from Baseline and cys-
mcMMAF Pharmacokinetic Concentration-Time Data 
See Listing 30.0720 in BMA117159 
((primary_01) 
SAC [1] 
COVID 19 
1.0082 
Full Safety 
PAN7 
Listing of All Subjects with Visits and Assessments Impacted 
by COVID-19 Pandemic 
 
SAC [2] 
 
 


 
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15.14. 
Appendix 14: Example Mock Shells for Data Displays 
 
Example POP_T1 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety 
 
                                                      (Data as of: 24APR2018) 
Table X 
Summary of Percentage of Duration of Exposure on Steroid Eye Drop  
 
 
Treatment Group 
A (N=100) 
Treatment Group 
B (N=100) 
% of duration of exposure [1] that was on 
Prophylactic steroid eye drop 
 
 
  n 
   100 
   100 
  Mean 
    20.5  
    15.1  
  SD 
    1.44 
    1.24 
  Median 
    18 
    14 
  Min. 
    3 
    1 
  Max. 
    40 
    30 
 
 
 
 
Note: 
1: Duration of Exposure in Days is calculated as minimum of (Treatment Stop Date+21, Death date) minus 
Treatment Start Date. 


 
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Example EFF_T1 
Protocol: 205678                                                                                Page 1 of 1 
Population: ITT 
 
                                                       
Table X.X 
Summary of MRD Negativity Rate by Best Response  
 
 
 
Treatment 
Group A 
(N=xx) 
Treatment 
Group B 
 (N=xx) 
Best response 
 
 
 
  Stringent Complete 
Response (sCR) 
n 
xx 
xx 
 
MRD Negativity Rate 
xx (xx.x%) 
xx (xx.x%) 
 
95% 
Confidence 
Interval 
(xx.x%, xx.x%) 
(xx.x%, xx.x%) 
 
 
 
 
 Complete 
Response 
(CR) 
n 
xx 
Xx 
 
MRD Negativity Rate 
xx (xx.x%) 
xx (xx.x%) 
 
95% 
Confidence 
Interval 
(xx.x%, xx.x%) 
(xx.x%, xx.x%) 
 
 
 
 
  Very Good Partial 
Response (VGPR) 
n 
xx 
xx 
 
MRD Negativity Rate 
xx (xx.x%) 
xx (xx.x%) 
 
95% 
Confidence 
Interval 
(xx.x%, xx.x%) 
(xx.x%, xx.x%) 
 
 
 
 
 sCR/CR/VGPR 
n 
xx 
xx 
 
MRD Negativity Rate 
xx (xx.x%) 
xx (xx.x%) 
 
95% 
Confidence 
Interval 
(xx.x%, xx.x%) 
(xx.x%, xx.x%) 
 
 
 
 
 
Note: Minimal Residual Disease (MRD) negativity rate is defined as: the percentage of participants who are MRD negative by 
Next Generation Sequencing (NGS). 
 


 
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Example EFF_T2 
Protocol: 205678                                                                                Page 1 of 1 
Population: Full Analysis 
 
                                                       
Table X.X 
Summary of Reasons of Censoring 
 
 
Time to event endpoints 
 
Treatment 
Group A 
(N=xx) 
Treatment 
Group B 
 (N=xx) 
 Duration of response(DoR) 
n 
xx 
xx 
 
Reason 1 
xx (xx.x%) 
xx (xx.x%) 
 
Reason 2 
xx (xx.x%) 
xx (xx.x%) 
 
Reason 3 
……… 
xx (xx.x%) 
xx (xx.x%) 
 
 
 
 
 Progression free 
survival(PFS) 
n 
xx 
xx 
 
Reason 1 
xx (xx.x%) 
xx (xx.x%) 
 
Reason 2 
xx (xx.x%) 
xx (xx.x%) 
 
Reason 3 
……… 
xx (xx.x%) 
xx (xx.x%) 
Time to progression(TTP) 
n 
xx 
xx 
 
Reason 1 
xx (xx.x%) 
xx (xx.x%) 
 
Reason 2 
xx (xx.x%) 
xx (xx.x%) 
 
Reason 3 
……… 
xx (xx.x%) 
xx (xx.x%) 
Overall survival(OS) 
n 
xx 
xx 
 
Reason 1 
xx (xx.x%) 
xx (xx.x%) 
 
Reason 2 
xx (xx.x%) 
xx (xx.x%) 
 
Reason 3 
……… 
xx (xx.x%) 
xx (xx.x%) 
n is the number of subject who were censored, which will be used as denominator to calculate the percentage. 
 


 
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150 
Example SAFE_T11 
Protocol: 205678                                                                                Page 1 of 1 
Population: Full Safety  
                                                       
Table X.X 
Summary of Thrombocytopenia and Bleeding Event 
 
Treatment 
Group A 
(N=100) 
Treatment 
Group B  
(N=100) 
Treatment  
Group C 
(N=100) 
 
 
 
 
Any Grade 3/4 Platelet Count Decreased 
  xx (xx.x%)   xx (xx.x%)   xx (xx.x%) 
Any Grade 2 or Above Bleeding Event 
  xx (xx.x%)   xx (xx.x%)   xx (xx.x%) 
Concomitant Platelet Count Decreased and 
Bleeding 
  xx (xx.x%)   xx (xx.x%)   xx (xx.x%) 
     
  xx (xx.x%)   xx (xx.x%)   xx (xx.x%) 
 


 
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Example SAFE_T11a 
Protocol: 205678                                                                                Page 1 of 1 
Population: Full Safety  
                                                       
Table X.X 
Summary of Neutropenia and Infection Event 
 
Treatment 
Group A 
(N=100) 
Treatment 
Group B  
(N=100) 
Treatment  
Group C 
(N=100) 
 
 
 
 
Any Grade 3/4 Neutrophil Count Decreased 
  xx (xx.x%)   xx (xx.x%)   xx (xx.x%) 
Any Infection Event 
  xx (xx.x%)   xx (xx.x%)   xx (xx.x%) 
Concomitant Neutrophil Count Decreased and 
Infection 
  xx (xx.x%)   xx (xx.x%)   xx (xx.x%) 
     
  xx (xx.x%)   xx (xx.x%)   xx (xx.x%) 
 


 
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152 
Example SAFE_T1 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety 
 
                                                       
Table X.X 
Summary of Corneal Events (GSK Scale) by Grade and Visit 
 
                                              Treatment Group A Treatment Group B     
                                                     (N=xx)         (N=xx)       
                    ---------------------------------------------------------- 
   Baseline Visit 
                       ANY EVENT                      xx (xx%)    xx (xx%)     
                       Grade 1                        xx (xx%)    xx (xx%)     
                       Grade 2                        xx (xx%)    xx (xx%)     
                       Grade 3                        xx (xx%)    xx (xx%)     
                       Grade 4                        xx (xx%)    xx (xx%)     
   Week 4 visit  
                       ANY EVENT                      xx (xx%)    xx (xx%)     
                       Grade 1                        xx (xx%)    xx (xx%)     
                       Grade 2                        xx (xx%)    xx (xx%)     
                       Grade 3                        xx (xx%)    xx (xx%)     
                       Grade 4                        xx (xx%)    xx (xx%)     
   Week 7 visit  
                       ANY EVENT                      xx (xx%)    xx (xx%)     
                       Grade 1                        xx (xx%)    xx (xx%)     
                       Grade 2                        xx (xx%)    xx (xx%)     
                       Grade 3                        xx (xx%)    xx (xx%)     
                       Grade 4                        xx (xx%)    xx (xx%)     
Note: Visits ‘Cycle X Day 1/Day 10’ are from ocular sub-study subjects only. ……………. 
 


 
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153 
Example SAFE_T1a 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety 
 
                                                       
Table X.X 
Summary of Cumulative Incidence of Corneal Events (GSK Scale) by Grade and Number of Doses Received at First Occurrence 
 
Treatment Group A (N=xx) 
 
                                ___________________Number of Doses Received at First Occurrence____________________ 
  Grade (GSK Scale)               <= 1        <= 2       <= 4      <= 6       <= 8       <= 10   Any  
----------------------------------------------------------------------------------------------------------- 
ANY Grade                        xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)    
  Grade 1                        xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)    
  Grade 2                        xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)    
  Grade 3                        xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)    
  Grade 4                        xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)   xx (xx%)    
 
Treatment Group B (N=xx) 
…………………… 


 
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154 
Example SAFE_T2 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety 
 
                                                       
Table X.X 
Summary of Action Taken with Study Treatment for Corneal Events (GSK Scale) by Visit 
 
 
Treatment Group A (N=xx) 
Visit 
 
n 
Grade 
Study treatment 
withdrawn 
Dose reduction 
Dose 
interrupted/  
delayed 
Week 4 
xx 
All Grade 
Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Grade 4 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
 
 
 
 
 
xx 
All Grade 
Grade 1 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Grade 2 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Grade 3 
xx (xx%) 
xx (xx%) 
xx (xx%) 
 
 
Grade 4 
xx (xx%) 
xx (xx%) 
xx (xx%) 
Week 7 
 
 
 
 
 
    ………… 
 
 
Treatment Group B (N=xx) 
………….. 
Note: n reflects the number of participants with available GSK scale data at a given visit.     
Visits ‘Cycle 1-4 Day 1/10’ are from ocular sub-study subjects only.  


 
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155 
Example SAFE_T2a 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety 
 
                                                       
Table X.X 
Summary of Corneal Events (GSK Scale) Leading to Action Taken with Study Treatment       
 
Action Taken with 
Study treatment 
Grade 
Treatment  
  Group A  
 (N = xx) 
Treatment  
  Group B  
 (N = xx) 
Study  
All Grades 
xx (xx%) 
xx (xx%) 
treatment  
Grade 1 
xx (xx%) 
xx (xx%) 
withdrawn 
Grade 2 
xx (xx%) 
xx (xx%) 
 
Grade 3 
xx (xx%) 
xx (xx%) 
 
Grade 4 
xx (xx%) 
xx (xx%) 
 
 
 
 
Dose reduction  
All Grades 
xx (xx%) 
xx (xx%) 
 
Grade 1 
xx (xx%) 
xx (xx%) 
 
Grade 2 
xx (xx%) 
xx (xx%) 
 
Grade 3 
xx (xx%) 
xx (xx%) 
 
Grade 4 
xx (xx%) 
xx (xx%) 
 
 
 
 
Dose interrupted/ 
delayed 
All Grades 
xx (xx%) 
xx (xx%) 
 
Grade 1 
xx (xx%) 
xx (xx%) 
 
Grade 2 
xx (xx%) 
xx (xx%) 
 
Grade 3 
xx (xx%) 
xx (xx%) 
 
Grade 4 
xx (xx%) 
xx (xx%) 
 
Note: If a given participant had multiple incidence of same action taken with study treatment, only the action 
with highest grade will be included in the summary. 


 
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156 
Example SAFE_T3 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety 
 
                                                      (Data as of: 24APR2018) 
Table X 
Shift in Grade of Corneal Events from Baseline to Worst Post-Baseline up to EOT visit  
 
Treatment Group 
Baseline 
Worst post-baseline value 
  
n (%) 
 
Grade 0 
 
n (%) 
 
Grade 1 
 
n (%) 
 
Grade 2 
 
n (%) 
 
Grade 3 
 
n (%) 
 
Grade 4 
 
n (%) 
 
Missing 
 
n (%) 
Treatment Group A (N=xx) Grade 0   xx (xx.x)  xx (xx.x)   xx (xx.x)   xx (xx.x)  xx (xx.x)   xx (xx.x)  xx (xx.x)  
                  
Grade 1   xx (xx.x)  xx (xx.x)   xx (xx.x)   xx (xx.x)  xx (xx.x)   xx (xx.x)  xx (xx.x)  
                  
Grade 2   xx (xx.x)  xx (xx.x)   xx (xx.x)   xx (xx.x)  xx (xx.x)   xx (xx.x)  xx (xx.x)  
                  
Grade 3   xx (xx.x)  xx (xx.x)   xx (xx.x)   xx (xx.x)  xx (xx.x)   xx (xx.x)  xx (xx.x)  
                  
Grade 4   xx (xx.x)  xx (xx.x)   xx (xx.x)   xx (xx.x)  xx (xx.x)   xx (xx.x)  xx (xx.x)  
                  
Missing   xx (xx.x)  xx (xx.x)   xx (xx.x)   xx (xx.x)  xx (xx.x)   xx (xx.x)  xx (xx.x)  
                  
Total     xx (xx.x)  xx (xx.x)   xx (xx.x)   xx (xx.x)  xx (xx.x)   xx (xx.x)  xx (xx.x)  
Treatment Group B (N=xx)   
  
  
  
  
  
  
  
.................. 
  
  
  
  
  
  
  
  
 
- Baseline percentage is based on N. percentage for last post-Baseline value is based on Baseline n. 
 
 


 
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Example SAFE_T4 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety 
 
                                                      (Data as of: 24APR2018) 
Table X 
Summary of Resolution Time from EOT in Best Corrected Visual Acuity (BCVA)  
 
Parameter = Best Corrected Visual Acuity (BCVA) 
 
Treatment  
Treatment  
Right eye: n [1] 
    100 
    100 
Number (%) of eyes that resolved [2] 
    50 (50%) 
    40 (40%) 
 
 
 
Time from EOT Visit to resolution, days  
 
 
  Mean 
    20.5  
    15.1  
  SD 
    1.44 
    1.24 
  Median 
    18 
    14 
  Min. 
    3 
    1 
  Max. 
    40 
    30 
 
 
 
 
Left eye: n [1] 
    100 
    100 
Number (%) of eyes that resolved [2] 
    50 (50%) 
    40 (40%) 
 
 
 
Time from EOT Visit to resolution, days  
 
 
 
 
 
  Mean 
    20.5  
    15.1  
  SD 
    1.44 
    1.24 
  Median 
    18 
    14 
  Min. 
    3 
    1 
  Max. 
    40 
    30 
 
 
 
Subject (worse eye): n [1] 
    100 
    100 
Number (%) of subjects that resolved [2] 
    50 (50%) 
    40 (40%) 
 
 
 
Time from EOT Visit to resolution, days  
 
 
 
 
 
  Mean 
    20.5  
    15.1  
  SD 
    1.44 
    1.24 
  Median 
    18 
    14 
  Min. 
    3 
    1 
  Max. 
    40 
    30 
 
 
 
Note: 
1: n is the number of eyes or subjects (worse eye) with exam result worse than baseline at EOT, which will be 
used as denominator to calculate the percentage.   
2: Resolution is defined as improvement to baseline level or better. 


 
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158 
Example SAFE_T4a 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety 
 
                                                      (Data as of: 24APR2018) 
Table X 
Summary of Resolution in Corneal Events (GSK Scale) during Follow-up Period 
 
 
Treatment Group 
A (N=100) 
Treatment Group 
B (N=100) 
 
 
 
n [1] 
   100 
   100 
Number (%) of Participants that Resolve[2] 
   50 (50%) 
   40 (40%) 
 
 
 
Time from EOT Visit to resolution[3], days   
 
  Mean 
    20.5  
    15.1  
  SD 
    1.44 
    1.24 
  Median 
    18 
    14 
  Min. 
    3 
    1 
  Max. 
    40 
    30 
 
 
 
 
Note: 
1: n reflects the number of participants who had corneal event (GSK Scale) with grade worse than baseline at 
EOT 
2: Resolution is defined as improvement to grade 1 or better 
3: Calculated as the date of resolution minus the (last dose date +20 days).  
 


 
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159 
Example SAFE_T4b 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety 
 
                                                      (Data as of: 24APR2018) 
Table X 
Summary of Time to Re-initiation of Study Treatment Post First Treatment Delay due to Corneal Events (GSK scale) 
 
 
 
Treatment Group 
A (N=100) 
Treatment Group 
B (N=100) 
 
 
 
Number (%) of subjects with treatment delay due 
to corneal event (GSK scale)  
   43 
   33 
   Re-initiation of study treatment 
   22 (51%) 
   19 (58%) 
 
 
 
Time to re-initiation [1], days  
 
 
  Mean 
    20.5  
    15.1  
  SD 
    1.44 
    1.24 
  Median 
    18 
    14 
  Min. 
    3 
    1 
  Max. 
    40 
    30 
 
 
 
 
Note: 
1: Time to re-initiation of study treatment is calculated as the date of first dose post treatment delay minus (the date of 
last dose prior to treatment delay +21). 
 


 
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Example SAFE_T5 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety                                                                  (Data as of: 24APR2018) 
Table x.xxxx 
Logistic regression analysis of possible risk factors for developing Corneal Events (GSK Scale) 
Variable 
OR 
95% CI 
P-value 
3.4 mg/kg vs. 2.5 mg/kg 
xx.x (xx.x, xx.x) 
0.xxx* 
Male vs. Female 
xx.x (xx.x, xx.x) 
0.xxx 
>= 65 vs. < 65 
xx.x (xx.x, xx.x) 
0.xxx 
Race 
xx.x (xx.x, xx.x) 
0.xxx 
 
xx.x (xx.x, xx.x) 
0.xxx 
 
xx.x (xx.x, xx.x) 
0.xxx 
 
 
 
 
 
xx.x (xx.x, xx.x) 
0.xxx 
Moderate/Severe vs. None 
xx.x (xx.x, xx.x) 
0.xxx 
* p<0.05 


 
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Example SAFE_T6 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety                                                                  (Data as of: 24APR2018) 
Table x.xxxx 
Summary of Change from Baseline in Refraction (Spherical Equivalent) 
Treatment Group A
Treatment grouop B
Timepoints
Eye
Refraction
(N=xxx)
(N=xxx)
Baseline
Right
Actual
n
xxx
xxx
Mean
x.x
x.x
SD
x.xx
x.xx
Median
x.x
x.x
Min
x
x
Max
xxx
xxx
Left
Actual
n
xxx
xxx
Mean
x.x
x.x
SD
x.xx
x.xx
Median
x.x
x.x
Min
x
x
Max
xxx
xxx
End of
Right
Change from Baseline
n
xxx
xxx
Mean
x.x
x.x
SD
x.xx
x.xx
Median
x.x
x.x
Min
x
x
Max
xxx
xxx
Left
Change from Baseline
n
xxx
xxx
Mean
x.x
x.x
SD
x.xx
x.xx
Median
x.x
x.x
Min
x
x
Max
xxx
xxx
Right
Absolute Change from
n
xxx
xxx
Mean
x.x
x.x
SD
x.xx
x.xx
Median
x.x
x.x
Min
x
x
Max
xxx
xxx
Right
Absolute Change from
n
xxx
xxx
Mean
x.x
x.x
SD
x.xx
x.xx
Median
x.x
x.x
Min
x
x
Max
xxx
xxx
 
Last follow-up 
Largest absolute 
Change from 
baseline


 
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Example SAFE_T7 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety                                                                  (Data as of: 24APR2018) 
Table x.xxxx 
Summary for Change from Baseline to Worst Post-Baseline in Schirmer's Test and Tear Break-up Time 
 
 
 
 Treatment Group A 
Treatment Group B 
Parameter 
 
  Statistics 
     (N=xxx) 
      (N=xxx) 
Schirmer's Test 
Right eye 
n 
xxx 
xxx 
(unit = mm) 
 
Mean 
x.x 
x.x 
 
 
SD 
x.xx 
x.xx 
 
 
Median 
x.x 
x.x 
 
 
Min 
x 
x 
 
 
Max 
xxx 
xxx 
 
Left eye 
n 
xxx 
xxx 
 
 
Mean 
x.x 
x.x 
 
 
SD 
x.xx 
x.xx 
 
 
Median 
x.x 
x.x 
 
 
Min 
x 
x 
 
 
Max 
xxx 
xxx 
 
 
 
 
 
Tear Break-up time 
Right eye 
n 
xxx 
xxx 
(unit = sec) 
 
Mean 
x.x 
x.x 
 
 
SD 
x.xx 
x.xx 
 
 
Median 
x.x 
x.x 
 
 
Min 
x 
x 
 
 
Max 
xxx 
xxx 
 
Left eye 
n 
xxx 
xxx 
 
 
Mean 
x.x 
x.x 
 
 
SD 
x.xx 
x.xx 
 
 
Median 
x.x 
x.x 
 
 
Min 
x 
x 
 
 
Max 
xxx 
xxx 


 
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163 
Example SAFE_T8 
Protocol: 205678                                                                             Page 1 of 1 
Population: Safety 
 
Table x.xxxx  
Summary of Intraocular Pressure (IOP) ≥ 22mm Hg Anytime Postbaseline 
Treatment  
Group A 
(N = 342) 
Treatment  
Group B 
(N = 365) 
Right eye 
n 
342 
364 
IOP ≥ 22mm Hg Anytime Post-
baseline 
 1 (<1%) 
2 (<1%) 
Left eye  
N 
342 
364 
IOP ≥ 22mm Hg Anytime Post-
baseline 
 1 (<1%) 
2 (<1%) 
Subject (either eye) 
n 
342 
364 
IOP ≥ 22mm Hg Anytime Post-
baseline 
 1 (<1%) 
2 (<1%) 
 


 
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164 
Example SAFE_T8a 
Protocol: 205678                                                                             Page 1 of 1 
Population: Safety 
 
Table x.xxx  
Summary of Subjects Who Start Treatment for Intraocular Pressure (IOP) after 1st Dose of Study Drug 
Treatment 
Group A 
(N = 342) 
Treatment  
Group B 
(N = 365) 
Subjects (n/%)Started Treatment 
for IOP after 1st Dose of Study 
Drug 
 1 (<1%) 
 2 (<1%) 
 


 
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165 
Example SAFE_T9 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety                                                                  (Data as of: 24APR2018) 
Table X 
Shift in Pupillary Exam Findings from Baseline to Worst Post-Baseline 
  
                       Treatment Group A 
 
 
Baseline  
 
       Worst Post-Baseline 
 
  
n (%) 
 
Category1 
 
n (%) 
 
Category 2 
 
n (%) 
 
Missing 
 
n (%) 
Right eye (N=xx)  
Category 1   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)  
                  
Category 2   xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)  
                  
Missing   
 xx (xx.x)   xx (xx.x)   xx (xx.x)   xx (xx.x)  
Left eye (N=xx) 
  
  
  
  
  
                  
 
 
 
 
 
Subject (Worse eye) (N = xx) 
  
  
  
  
  
                  
 
 
 
 
 
Both eyes at same exam (N = xx) 
 
 
 
 
 
- Baseline percentage is based on N. percentage for worst post-Baseline value is based on Baseline n. 
           Treatment Group B 
            …………………….. 
Programming note: ‘Right eye’ and ‘Left eye’ are always included. ‘Worst eye’ and ‘Both eye’ are optional 
based on the programming note.  


 
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166 
Example SAFE_T9a 
Protocol: 205678                                                                                Page 1 of 1 
Population: Full Safety                                                               (Data as of: 24APR2018) 
Table X 
Shift in Schirmer’s Test from Baseline to Worst Post-Baseline 
  
 Treatment Group A 
 
 
Baseline  
 
       Worst Post-Baseline 
 
 
  
n (%) 
 
Category1 
 
n (%) 
 
Category 2 
 
n (%) 
 
Category 3 
 
n (%) 
 
Missing 
 
n (%) 
Right eye (N=xx)  
Category 1  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
Category 2  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
Category 3  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
Missing   
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
Left eye (N=xx)  
Category 1  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
Category 2  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 
Category 3  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 
Missing   
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
Note: Baseline percentage is based on N. percentage for worst post-Baseline value is based on Baseline n.  
Treatment Group B 
            …………………….. 


 
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167 
Example SAFE_T10 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety 
 
                                                      (Data as of: 24APR2018) 
Table x.xxxx 
Summary for Change from Baseline in Pachymetry 
 
 
Treatment  
 Group A 
(N=100) 
  Treatment  
 Group B 
(N=100) 
 
 
 
 
Right eye  
n[1] 
100 
100 
 
    Number (%) of ≥ 5% increase  
    from baseline at worst post- 
    baseline 
50 (50%) 
70 (70%) 
 
Left eye 
n [1] 
100 
100 
 
    Number (%) of ≥ 5% increase 
    from baseline at worst post- 
    baseline 
50 (50%) 
70 (70%) 
 
 
 
 
Subject (either eye) 
n 
100 
100 
 
    Number (%) of ≥ 5% increase 
    from baseline at worst post-  
    baseline 
50 (50%) 
50 (50%) 
 
Note:  n is the number of eyes/subjects with baseline and at least one post baseline value.  
Example SAFE_T12 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety                                                                  (Data as of: 24APR2018) 
Table x.xxxx 
Summary of Presence of Descemet’s Folds/Endothelial Lesions at Any Time Post-baseline 
 
 
 
Treatment Group 
A (N=100) 
Treatment Group 
B (N=100) 


 
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168 
 
Right eye 
 
n  
Descemet’s fold 
Endothelial lesions 
 
 
60   
25 (42%) 
45 (75%) 
 
54 
34 (63%) 
48 (89%) 
 
Left eye 
 
n 
Descemet’s fold 
Endothelial lesions 
 
 
56 
23 (41%) 
42 (75%) 
 
 
61 
37 (61%) 
53 (87%) 
 
 
Subject 
(either eye) 
 
n 
Descemet’s fold 
Endothelial lesions 
 
 
56 
23 (41%) 
42 (75%) 
 
 
61 
37 (61%) 
53 (87%) 
 
 
Right eye 
 
n  
Descemet’s fold 
Endothelial lesions 
 
 
60   
25 (42%) 
45 (75%) 
 
54 
34 (63%) 
48 (89%) 
 


 
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169 
Example SAFE_T13 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety                                                                  (Data as of: 24APR2018) 
Table x.xxxx 
Shift in Albumin Creatinine Ratio (mg/g) from Baseline to Worst Post-Baseline 
  
 
Baseline  
 
       Worst Post-Baseline 
 
  
n (%) 
 
< 500 
 
n (%) 
 
[500, 2000] 
 
n (%) 
 
> 2000    
 
n (%) 
Treatment Group A (N=xx)  
< 500  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
                  
[500, 2000]  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
                  
> 2000    
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
 xx (xx.x)  
Treatment Group B (N=xx) 
  
  
  
  
  
                  
 
 
 
 
 
Treatment Group C (N=xx) 
  
  
  
  
  
                  
 
 
 
 
 
- Baseline percentage is based on N. percentage for worst post-Baseline value is based on Baseline n. 
 


 
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170 
Example SAFE_T14 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety                                                                  (Data as of: 24APR2018) 
Table x.xxxx 
Summary of Findings for Punctate Keratopathy 
 
 
 
Dose Arm A 
(N=100) 
Dose Arm B 
(N=100) 
 
 
 
 
Right eye 
n 
Worst grade among exams 
 
Mild 
Moderate 
Severe 
 
 
100 
   
5  (5%) 
34 (34%) 
46 (46%) 
15 (15%) 
  
100 
    
10 (10%) 
17 (17%) 
23 (23%) 
50 (50%) 
 
 
 
Most frequent grade among exams  
None 
Mild 
Moderate 
Severe 
 
 
 
  5  (5%) 
  
5  (5%) 
34 (34%) 
46 (46%) 
 
 
 
   10 (10%) 
 
10 (10%) 
17 (17%) 
23 (23%) 
 
 
Left eye 
 
 
 
               …………….. 
               Subject (worse eye) 
               …………… 
 
1: n reflects the number of eyes with Punctate keratopathy worse than baseline at any post-baseline ocular 
exam 


 
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171 
Example SAFE_T15 
Protocol: 205678                                                                             Page 1 of 1 
Population: Safety 
Table x.xxxx 
Summary of Change (Worsening, No Change, Improvement) in Best Corrected Visual Acuity (BCVA) from EOT Visit to 
Last Follow-up Visit 
Change Category 
Treatment 
Group A 
(N = 342) 
Treatment 
Group B 
(N = 365) 
Right eye 
n 
342 
364 
Worsening 
 1 (<1%) 
 2 (<1%) 
No Change  
330 (96%) 
359 (98%) 
Improvement 
11  (3%) 
 4  (1%) 
 
 
Left eye 
n 
342 
364 
Worsening 
 1 (<1%) 
 2 (<1%) 
No Change  
330 (96%) 
359 (98%) 
Improvement 
11  (3%) 
 4  (1%) 
 
 
Subject (Worse eye) 
n 
342 
364 
Worsening 
 1 (<1%) 
 2 (<1%) 
No Change  
330 (96%) 
359 (98%) 
Improvement 
11  (3%) 
 4  (1%) 
 
 
 
 
n is the number of eyes or subjects (worse eye) with exam findings at EOT visit worse than baseline, which 
will be used as denominator to calculate the percentage. 


 
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172 
Example SAFE_T16 
Protocol: 205678                                                                             Page 1 of n 
Population: Safety 
Table x.xxxx 
Summary of Worst Grade of Corneal Events (GSK Scale) during Cycle 1-4 by Randomized Topical Corticosteroids 
Treatment 
  
 
 
 
 
             Treatment Group A (N = xx)              Treatment Group B (N = xx)          
Timepoint 
 
 
 Eyes 
randomized  
 to 
corticosteroids 
 
Eye randomized 
to no 
corticosteroids 
   Eyes 
randomized  
 to 
corticosteroids 
 
Eyes not randomized 
to corticosteroids 
 
 
 
 
 
 
Baseline 
n 
100 
100 
100 
100 
 
Grade 0 
70 (70%) 
70 (70%) 
70 (70%) 
70 (70%) 
 
Grade 1 
20 (20%) 
20 (20%) 
20 (20%) 
20 (20%) 
 
Grade 2 
10 (10%) 
10 (10%) 
10 (10%) 
10 (10%) 
 
Grade 3 
0 
0 
0 
0 
 
Grade 4 
0 
0 
0 
0 
 
 
 
 
 
 
Worst during 
n 
100 
100 
100 
100 
Cycle 1-4 
Grade 0 
70 (70%) 
70 (70%) 
70 (70%) 
70 (70%) 
 
Grade 1 
20 (20%) 
20 (20%) 
20 (20%) 
20 (20%) 
 
Grade 2 
10 (10%) 
10 (10%) 
10 (10%) 
10 (10%) 
 
Grade 3 
0 
0 
0 
0 
 
Grade 4 
0 
0 
0 
0 


 
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173 
Example SAFE_T17 
Protocol: 205678                                                                             Page 1 of n 
Population: Safety 
Table x.xxxx 
Summary of Best Corrected Visual Acuity(BCVA) score (logMAR score) during Cycle 1-4 by Randomized Topical 
Corticosteroids Treatment  
 
 
                                     Treatment Group A (N =xx)          Treatment Group B (N =xx)    
 
 
Eyes 
Eye not 
Eyes Randomized 
Eyes not 
Timepoint 
BCVA Score 
  
 to 
to 
 to 
Baseline 
N 
    xxx 
    xxx 
    xxx 
    xxx 
 
Mean 
      x.x 
      x.x 
      x.x 
      x.x 
 
SD 
      x.xx 
      x.xx 
      x.xx 
      x.xx 
 
Median 
      x.x 
      x.x 
      x.x 
      x.x 
 
Min 
      x 
      x 
      x 
      x 
 
Max 
      xxx 
      xxx 
      xxx 
      xxx 
 
 
 
 
 
 
Worst during 
n 
    xxx 
    xxx 
    xxx 
    xxx 
Cycle 1-4 
Mean 
      x.x 
      x.x 
      x.x 
      x.x 
 
SD 
      x.xx 
      x.xx 
      x.xx 
      x.xx 
 
Median 
      x.x 
      x.x 
      x.x 
      x.x 
 
Min 
      x 
      x 
      x 
      x 
 
Max 
      xxx 
      xxx 
      xxx 
      xxx 
 
n 
    xxx 
    xxx 
    xxx 
    xxx 
 
 
 
 
 
 
Worst change  
No change/improve 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
from baseline 
Possible worsened 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
during Cycle 1-
Definite worsened 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
 
 
 
 
 
 
Most frequent 
No change/improve 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
change from 
Possible worsened 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
baseline during 
Definite worsened 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
cycle 1-4 
 
      
       
       
       
 
 
 
 
 
 
Worst during 
BCVA decline to 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
Cycle 1-4 
light perception 
 
 
 
 
 
 
 
 
 
 
 
BCVA decline to 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
xx(x.x%) 
 
no light perception 
 
 
 
 
 
 
 
 
 
 
Note: No change/improved vision is defined as a change from baseline <0.12; a possible worsened vision is 
defined as a change from baseline >=0.12 to <0.3; a definite worsened vision is defined as a change from 
baseline >=0.3 logMAR score. 


 
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174 
Example SAFE_T18 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety                                                                  (Data as of: 24APR2018) 
Table x.xxxx 
Summary of Onset Time to First Drug-Related Corneal Event (GSK Scale) by Randomized Topical Corticosteroids 
Treatment 
 
 
                                      Treatment Group A (N=xx)           Treatment Group B (N=xx)        
 
Eyes randomized 
to 
corticosteroids 
Eyes randomized to 
no corticosteroids  
Eyes randomized 
to 
corticosteroids 
Eyes randomized to 
no corticosteroids 
 
 
 
 
 
Number (%) of eyes 
experienced drug-related 
corneal event (GSK scale)  
   5 (50%) 
   4 (40%) 
   4 (40%) 
   5 (50%) 
 
 
 
 
 
Time to initiation, days  
 
 
 
 
n 
    5  
    5  
    5  
    5  
1-21 
    1 (20%) 
    1 (20%) 
    1 (20%) 
    1 (20%) 
22-42 
    2 (40%) 
    2 (40%) 
    2 (40%) 
    2 (40%) 
43-63 
    1 (20%) 
    1 (20%) 
    1 (20%) 
    1 (20%) 
> 63 
    1 (20%) 
    1 (20%) 
    1 (20%) 
    1 (20%) 
  Mean 
    20.5  
    15.1  
    15.1  
    20.5  
  SD 
    1.44 
    1.24 
    1.24 
    1.44 
  Median 
    18 
    14 
    14 
    18 
  Min. 
    3 
    1 
    1 
    3 
  Max. 
    40 
    30 
    30 
    40 
 


 
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175 
Example SAFE_T19 
Protocol: 205678                                                                                Page 1 of 1 
Population: Ocular Sub-Study  
                                                (Data as of: 24APR2018) 
Table x.xxxx 
Summary of Onset Time to Initiation of Topical Corticosteroids Treatment in Eyes Not Randomized to Topical 
Corticosteroids Treatment  
 
 
 
Treatment  
  Group A 
(N = xx) 
Treatment  
  Group B 
(N = xx) 
 
 
 
Number (%) of eyes that initiated 
topical Corticosteroids Treatment  
   5 (50%) 
   4 (40%) 
 
 
 
Time to initiation, days  
 
 
n 
    5  
    5  
1-21 
    1 (20%) 
    1 (20%) 
22-42 
    2 (40%) 
    2 (40%) 
43-63 
    1 (20%) 
    1 (20%) 
> 63 
    1 (20%) 
    1 (20%) 
  Mean 
    20.5  
    15.1  
  SD 
    1.44 
    1.24 
  Median 
    18 
    14 
  Min. 
    3 
    1 
  Max. 
    40 
    30 
 
 
 
Note: 
1: N reflects the number of eyes randomized to no topical corticosteroids treatment for ocular sub-study.  


 
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176 
Example SAFE_T20 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety                                                                  (Data as of: 24APR2018) 
Table x.xxxx 
Shift in Corneal Events (per Ocular Exam) from Baseline to Worst During Cycle 1-4 by Randomized Topical 
Corticosteroids Treatment 
 
 
 
 Treatment Group A (N = xx) 
   Treatment Group B (N= xx) 
Exam 
 
Shift from Baseline 
to Worst (Cycle 1-4) 
Eyes randomized to 
corticosteroids 
Eyes not randomized  
to corticosteroids 
Eyes randomized to 
Corticosteroids 
Eyes not randomized 
to corticosteroids 
 
 
 
 
 
 
Corneal  
n 
100 
100 
100 
100 
Epithelium 
Normal to Normal 
30 (30%) 
30 (30%) 
30 (30%) 
30 (30%) 
 
Normal to Abnormal 
50 (50%) 
50 (50%) 
50 (50%) 
50 (50%) 
 
Abnormal to Normal 
0 
0 
0 
0 
 
Abnormal to Abnormal 20 (20%) 
20 (20%) 
20 (20%) 
20 (20%) 
 
 
 
 
 
 
Punctate Keratopathy n 
100 
100 
100 
100 
 
None/Mild to  
None/Mild 
30 (30%) 
30 (30%) 
30 (30%) 
30 (30%) 
 
None/Mild to  
Moderate/Severe 
50 (50%) 
50 (50%) 
50 (50%) 
50 (50%) 
 
Moderate/Severe to  
None/Mild 
0 
0 
0 
0 
 
Moderate/Severe to  
Moderate/Severe 
20 (20%) 
20 (20%) 
20 (20%) 
20 (20%) 
 
 
 
 
 
 
Corneal Ulcer 
n 
100 
100 
100 
100 
 
Normal to Normal 
30 (30%) 
30 (30%) 
30 (30%) 
30 (30%) 
 
Normal to Abnormal 
50 (50%) 
50 (50%) 
50 (50%) 
50 (50%) 
 
Abnormal to Normal 
0 
0 
0 
0 
 
Abnormal to Abnormal 20 (20%) 
20 (20%) 
20 (20%) 
20 (20%) 
 
 
 
 
 
 
Microcystic Edema 
n 
100 
100 
100 
100 
 
No to No 
30 (30%) 
30 (30%) 
30 (30%) 
30 (30%) 
 
No to Yes 
50 (50%) 
50 (50%) 
50 (50%) 
50 (50%) 
 
Yes to No 
0 
0 
0 
0 
 
Yes to Yes 
20 (20%) 
20 (20%) 
20 (20%) 
20 (20%) 
 
 
 
 
 
 


 
CONFIDENTIAL 
 
 
 
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Microcystic 
n 
100 
100 
100 
100 
Without Edema 
No to No 
30 (30%) 
30 (30%) 
30 (30%) 
30 (30%) 
 
No to Yes 
50 (50%) 
50 (50%) 
50 (50%) 
50 (50%) 
 
Yes to No 
0 
0 
0 
0 
 
Yes to Yes 
20 (20%) 
20 (20%) 
20 (20%) 
20 (20%) 
 
 
 
 
 
 
 
 
 
 
 
 
Subepithelial 
n 
100 
100 
100 
100 
Haze 
No to No 
30 (30%) 
30 (30%) 
30 (30%) 
30 (30%) 
 
No to Yes 
50 (50%) 
50 (50%) 
50 (50%) 
50 (50%) 
 
Yes to No 
0 
0 
0 
0 
 
Yes to Yes 
20 (20%) 
20 (20%) 
20 (20%) 
20 (20%) 
 
 
 
 
 
 
 
 
 
 
 
 
Corneal 
n 
100 
100 
100 
100 
Neovascularization 
No to No 
30 (30%) 
30 (30%) 
30 (30%) 
30 (30%) 
 
No to Yes 
50 (50%) 
50 (50%) 
50 (50%) 
50 (50%) 
 
Yes to No 
0 
0 
0 
0 
 
Yes to Yes 
20 (20%) 
20 (20%) 
20 (20%) 
20 (20%) 
 
 
 
 
 
 
Stroma 
n 
100 
100 
100 
100 
 
Normal to Normal 
30 (30%) 
30 (30%) 
30 (30%) 
30 (30%) 
 
Normal to Abnormal 
50 (50%) 
50 (50%) 
50 (50%) 
50 (50%) 
 
Abnormal to Normal 
0 
0 
0 
0 
 
Abnormal to Abnormal 20 (20%) 
20 (20%) 
20 (20%) 
20 (20%) 
 
 
 
 
 
 
Active Opacity 
n 
100 
100 
100 
100 
 
No to No 
30 (30%) 
30 (30%) 
30 (30%) 
30 (30%) 
 
No to Yes 
50 (50%) 
50 (50%) 
50 (50%) 
50 (50%) 
 
Yes to No 
0 
0 
0 
0 
 
Yes to Yes 
20 (20%) 
20 (20%) 
20 (20%) 
20 (20%) 
 
 
 
 
 
 
Active Edema 
n 
100 
100 
100 
100 
 
No to No 
30 (30%) 
30 (30%) 
30 (30%) 
30 (30%) 
 
No to Yes 
50 (50%) 
50 (50%) 
50 (50%) 
50 (50%) 
 
Yes to No 
0 
0 
0 
0 
 
Yes to Yes 
20 (20%) 
20 (20%) 
20 (20%) 
20 (20%) 
 
 
 
 
 
 


 
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178 
Example SAFE_T21 
Protocol: 205678                                                                                Page 3 of 3 
Population: Full Safety  
                                                       
Table x.xxxx 
Summary of Blurred Vision (CTCAE) Characteristics II 
 
2.5 mg/kg (N= xx) 
3.4 mg/kg (N= xx) 
3.4 mg/kg (N= xx) 
Time to onset of first occurrence, days 
n 
xx 
xx 
xx 
Mean 
xx.x 
xx.x 
xx.x 
SD 
xx.xx 
xx.xx 
xx.xx 
Median 
xx.x 
xx.x 
xx.x 
Min. 
xx 
xx 
xx 
Max. 
xx 
xx 
xx 
 1 - 21 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 22 - 42 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 43 - 63 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 64 - 105 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
     >105 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Outcome of first occurrence [1] (n=xx) 
Resolved  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  re-started with dose delay and reduction  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  re-started with dose delay but no 
reduction 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  re-started with dose reduction but no 
delay 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  re-started without dose delay or 
reduction 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  not re-started 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Not resolved, re-started 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 


 
CONFIDENTIAL 
 
 
 
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  with dose delay and reduction  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  with dose delay but no reduction 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  with dose reduction but no delay 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  without dose delay or reduction  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
Not resolved, not re-started  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  not discontinued  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  discontinued, follow up ongoing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
  discontinued, follow up ended 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Duration of first occurrence [1] [2] 
    n 
xx 
xx 
xx 
    Mean 
xx.x 
xx.x 
xx.x 
    SD 
xx.xx 
xx.xx 
xx.xx 
    Median 
xx.x 
xx.x 
xx.x 
    Min. 
xx 
xx 
xx 
    Max. 
xx 
xx 
xx 
Number of occurrences (based on subjects 
with the event) 
   One  
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Two 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Three or more 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Outcome post treatment exposure 
xx 
xx 
xx 
   Number of of subjects with unresolved    
   Event at the end of treatment exposure,  
   or with event onset post treatment  
   exposure. 
   Resolved 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
   Not resolved, follow up ongoing 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 


 
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180 
   Not resolved, follow up ended 
xx (xx.x%) 
xx (xx.x%) 
xx (xx.x%) 
 
Time to resolution post treatment 
exposure, days 
    n 
xx 
xx 
xx 
    Mean 
xx.x 
xx.x 
xx.x 
    SD 
xx.xx 
xx.xx 
xx.xx 
    Median 
xx.x 
xx.x 
xx.x 
    Min. 
xx 
xx 
xx 
    Max. 
xx 
xx 
xx 
[1] The duration is defined as time from onset of any blurred vision event to the first time the subject is free of any such event. It requires at least one day gap 
between the resolution of all events from first occurrence to the onset of second occurrence.  
[2] Imputed AE stop date was used in the calculation of duration if the outcome of the event was resolved/resolved with sequalae and AE stop date was partial with 
day missing. Imputed AE start date was used in the calculation if the start date was partial with day missing. 
[3] The end of treatment exposure is defined as last infusion date +20 days.  
Programming note:  
a. The event term (e.g. blurred vision) in footnote 1 need to be updated to be consistent with the title. b. Time to resolution post treatment exposure is calculated as 
(AE end date – end of treatment exposure) if there is unresolved event at the end of treatment exposure, or (first time the subject is free of any such event – onset 
date) if there is no unresolved event at the end of treatment exposure but with event onset post treatment exposure. 


 
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181 
Example SAFE_T22 
Protocol: 205678                                                                                Page 1 of 1 
Population: Full Safety  
                                                       
Table x.xxxx 
 
      Summary of Percentage of Duration of Exposure with Blurred Vision (CTCAE) 
 
                                                  2.5 mg/kg        3.4 mg/kg        3.4 mg/kg Lyo 
                                                  (N=97)           (N=96)           (N=25) 
        ------------------------------------------------------------------------------------------- 
        Percentage of Duration of Exposure 
          n                                       48               31               11 
          Mean                                    52.9             46.8             42.8 
          SD                                      24.31            28.00            24.27 
          Median                                  55.4             51.2             48.8 
          Min.                                     2                2                5 
          Max.                                    95               89               75 
 
        Category of Percentage of Duration of 
        Exposure 
          n                                       48               31               11 
          >0 to <=20%                              6 (13%)          8 (26%)          3 (27%) 
          > 20% to <= 40%                          8 (17%)          6 (19%)          1  (9%) 
          > 40% to <= 60%                         13 (27%)          4 (13%)          3 (27%) 
          > 60% to <= 80%                         13 (27%)          9 (29%)          4 (36%) 
          > 80% to <= 100%                         8 (17%)          4 (13%)          0 
 
Note: n denotes the number of subjects with corneal events (CTCAE) of maximum grade >= 2 
during exposure of study treatment. 
 


 
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182 
Example: PRO_T1 
Protocol: 205678                                                                               Page 1 of 1 
Population: ITT 
 
 
 
 
 
 
 
 
          (Data as of: 30MAY2001) 
Table x.xxxx 
Summary of Change in EORTC QLQ-C30/EORTC QLQ-MY20 Summary Score/Domain Scores from Baseline by Visit 
summary score/domain score names (Physical Functioning, Role Functioning, etc)     
 
 
 
Treatment Group A 
Treatment Group B 
Timepoint 
 
 
    (N=xxx) 
    (N=xxx) 
Baseline 
Actual Score 
n 
     xxx 
     xxx 
 
 
Mean 
      x.x 
      x.x 
 
 
SD 
      x.xx 
      x.xx 
 
 
Median 
      x.x 
      x.x 
 
 
Min 
      x 
      X 
 
 
Max 
      xxx 
      xxx 
Week 4 
Actual Score 
n 
    xxx 
    xxx 
 
 
Mean 
      x.x 
      x.x 
 
 
SD 
      x.xx 
      x.xx 
 
 
Median 
      x.x 
      x.x 
 
 
Min 
      x 
      x 
 
 
Max 
      xxx 
      xxx 
 
Change from Baseline 
n 
    xxx 
    xxx 
 
 
Mean 
      x.x 
      x.x 
 
 
SD 
      x.xx 
      x.xx 
 
 
Median 
      x.x 
      x.x 
 
 
Min 
      x 
      x 
 
 
Max 
      xxx 
      xxx 
Week x 
Actual Score 
n 
    xxx 
    xxx 
 
 
Mean 
      x.x 
      x.x 
 
 
SD 
      x.xx 
      x.xx 
 
 
Median 
      x.x 
      x.x 
 
 
Min 
      x 
      x 
 
 
Max 
      xxx 
      xxx 
 
 
 
 
 
 
Change from Baseline 
n 
    xxx 
    xxx 
 
 
Mean 
      x.x 
      x.x 
 
 
SD 
      x.xx 
      x.xx 
 
 
Median 
      x.x 
      x.x 
 
 
Min 
      x 
      x 
 
 
Max 
      xxx 
      xxx 


 
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183 
Example: PRO_T2 
Protocol: 205678                                                                               Page 1 of 1 
Population: ITT 
 
 
 
 
 
 
 
 
          (Data as of: 30MAY2001) 
 
Table x.xxxx 
Number (%) of patient with improvement in EORTC QLQ-C30EORTC QLQ-MY20 summary score/domain scores  5/10/MID by visit 
 
summary score/domain score names (Physical Functioning, Role Functioning, etc)     
 
 
Treatment  
Group A 
Treatment  
Group B 
Timepoint 
 
(N=xxx) 
(N=xxx) 
Week 4 
N 
    xxx 
    xxx 
 
summary score/domain scores  5/10/MID 
    xxx(xx%) 
    xxx(xx%) 
 
 
 
 
Week x 
n 
    xxx 
    xxx 
 
summary score/domain scores  5/10/MID 
    xxx(xx%) 
    xxx(xx%) 
 


 
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184 
Example: PRO_T3 
Protocol: 205678                                                                               Page 1 of 1 
Population: Safety  
 
 
 
 
 
 
 
          (Data as of: 30MAY2001) 
 
Table x.xxxx 
Summary of maximum post-baseline PRO-CTCAE score 
 
 
Treatment Group A 
 
Treatment Group B 
 
(N=xxx) 
 
(N=xxx) 
 
Frequency 
Severity 
Interferenc
e
 
Frequency 
Severity 
Interferenc
e
 
 
 
 
 
 
 
 
Item x 
n=xxx 
n=xxx 
n=xxx 
 
n=xxx 
n=xxx 
n=xxx 
Response 
 
 
 
 
 
 
 
0 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
1 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
2 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
3 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
4 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
3+4 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
Any Scale >0 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
 
 
 
 
 
 
 
Item y 
n=xxx 
n=xxx 
n=xxx 
 
n=xxx 
n=xxx 
n=xxx 
Response Scale 
 
 
 
 
 
 
 
0 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
1 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
2 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
3 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
4 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
3+4 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
Any Scale >0 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
xx(xx%) 
xx(xx%) 
xx(xx%) 
 
Note: For frequency levels, response scale stands for: 0-Never, 1-Rarely, 2-Occasionally, 3-Frequently, 4-Almost 
Constantly;for severity levels, response scale stands for: 0-None, 1-Mild, 2-Moderate, 3-Severe, 4-Very severe; for 
interference levels, response scale stands for: 0-Not at all, 1-A little bit, 2-Somewhat, 3-Quite a bit, 4-Very much. 
Note: n1-n3 are the number of participants with at least one post-baseline response scale of the three attributes for a 
given item, which are used as denominator for calculation of percentage.  


 
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185 
Example: PRO_T4 
Protocol: 205678                                                                               Page 1 of 1 
Population: ITT 
 
 
 
 
 
 
 
 
          (Data as of: 30MAY2001) 
 
Table x.xxxx 
Summary of Worst Change from Baseline in NEI-VFQ-25 Overall Composite Score by Worst Grade of Corneal Event (GSK Scale)  
 
 
 
          Frozen Liquid (2.5 + 3.4 mg/kg) + Lyo (3.4 mg/kg) 
 
 
 
    Worst Grade = 0 
 Worst Grade = 1,2 
Worst Grade = 3,4 
 
 
 
(N=xxx) 
(N=xxx) 
(N=xxx) 
Baseline 
Actual Score 
n 
xx 
xx 
xx 
 
 
Mean 
x.x 
x.x 
x.x 
 
 
SD 
x.xx 
x.xx 
x.xx 
 
 
Median 
x.x 
x.x 
x.x 
 
 
Min 
x.x 
x.x 
x.x 
 
 
Max 
xx.x 
xx.x 
xx.x 
Worst  
Actual Score 
n 
xx 
xx 
xx 
Post-baseline 
 
Mean 
x.x 
x.x 
x.x 
 
 
SD 
x.xx 
x.xx 
x.xx 
 
 
Median 
x.x 
x.x 
x.x 
 
 
Min 
x.x 
x.x 
x.x 
 
 
Max 
xx.x 
xx.x 
xx.x 
 
Change from Baseline 
n 
xx 
xx 
xx 
 
 
Mean 
x.x 
x.x 
x.x 
 
 
SD 
x.xx 
x.xx 
x.xx 
 
 
Median 
x.x 
x.x 
x.x 
 
 
Min 
x.x 
x.x 
x.x 
 
 
Max 
xx.x 
xx.x 
xx.x 
 


 
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186 
Example: PRO_F1 
Protocol: 205678                                                                               Page 1 of 1 
Population: Safety  
 
 
 
 
 
 
 
          (Data as of: 30MAY2001) 
Figure x.xxxx 
Stacked Bar Chart of PRO-CTCAE Score by Attributes and Visit 
Item X  
Frequency/Severity/Interference 
 
Programming note: There is flexibility in choosing colour. 


 
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187 
Example SAFE_L2 
Protocol: 205678                                                                                Page 1 of 1 
Population: Safety 
 
                                                      (Data as of: 24APR2018) 
Listing X 
Listing of Corneal Findings (GSK Scale) 
 
Treatment Group A 
 
 
 
Centre 
Id/ 
Subj. 
 
 
 
Age(y)
/ 
Sex/ 
Race 
Eye 
 
 
 
 
Grade/ 
Exam Finding(s) 
Overall Grade of 
Corneal Examination 
Findings/Visual 
Acuity 
Grade/Overall Grade 
for GSK Scale for 
this eye 
 
Date of 
Assessment
/Visit 
Time 
Since 
1st 
Dose/ 
Last 
Dose 
 
Action(s) Taken 
with study 
treatment/ 
Related 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
Left 
Grade 2/ Moderate 
keratopathy, Grade 
3/Diffuse Epithelial 
or stromal edema 
Grade 3/ Not 
Applicable/ Grade 3 
/ 
Week 4 
  15 
d/ 
  10 d 
Dose reduced, Dose 
interrupted/delaye
d/ 
No 
 
 
 
 
 
 
 
 
 
 
Right 
Grade 3/ Diffuse 
microcysts 
Grade 3/ Grade 1/ 
Grade 3 
/ 
Week 4 
 
  30 
d/ 
   0 d  
Dose 
interrupted/delaye
d/ 
Yes 
 
 
 
 
 
 
 
 
 
 
Left 
Grade 1/Mild 
superficial 
keratopathy 
Grade 1/ Not 
Applicable/ Grade 1 
/ 
Week 7 
  32 
d/ 
   0 d 
Dose 
interrupted/delaye
d / 
No 
 
 
Right 
Grade 1/Mild 
superficial 
keratopathy 
Grade 1/ Not 
Applicable/ Grade 1 
/ 
Week 7 
  32 
d/ 
   0 d 
Dose 
interrupted/delaye
d /No 
Treatment Group B 
…………………………….. 
Treatment Group C  
……………….. 
PPD
PPD
PPD
PPD
PPD
PPD