Clinical trial NCT06160609
Conditions: Relapsed/Refractory Multiple Myeloma
Sponsor: GlaxoSmithKline
Start date: 2019-10-07; Completion date: 2023-01-09
Enrollment: 9 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The primary purpose is to determine the safety and tolerability of belantamab mafodotin in combination with other anti-cancer treatments (in each sub-study), and to establish the recommended Phase 2 dose for each combination treatment to explore in the cohort expansion phase. This study is the sub study of the Master protocol (NCT04126200).

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: Belantamab Mafodotin intervention 2: GSK3174998
Intervention descriptions: intervention 1: Belantamab Mafodotin will be administered. intervention 2: GSK3174998 will be administered.

Protocol documents:
Prot_002.pdf: 
Protocol Amendment 4
Study ID:  208887 Sub Study 1
Official Title of Sub Study 1: A Phase I/II, Randomized, Open-label Platform 
Study 
Utilizing 
a 
Master 
Protocol 
to 
Study 
Belantamab 
Mafodotin 
(GSK2857916) 
as 
Monotherapy 
and 
in 
Combination 
With 
Anti-Cancer 
Treatments in Participants With Relapsed/Refractory Multiple Myeloma (RRMM)-
DREAMM5. Sub-study 1 - Belantamab Mafodotin and aOX40 (GSK3174998) in 
Combination
NCT ID of Sub Study 1: NCT06160609
Date of Document: 14-DEC-2020 
NCT ID of Master Protocol: NCT04126200


2020N453267_00 
CONFIDENTIAL 
 
GlaxoSmithKline group of companies 
 
208887 Sub-study 1 
 
1 
 
TITLE PAGE 
Protocol Title: A Phase I/II, Randomized, Open-label Platform Study Utilizing a Master 
Protocol to Study Belantamab Mafodotin (GSK2857916) as Monotherapy and in 
Combination with Anti-Cancer Treatments in Participants with Relapsed/Refractory 
Multiple Myeloma (RRMM)–DREAMM5. Sub-study 1 – Belantamab Mafodotin and 
aOX40 (GSK3174998) in Combination 
Protocol Number: 208887 Sub-study 1 / Amendment 04 
Compound Number 
or Name: 
Belantamab mafodotin (GSK2857916), GSK3174998 
Short Title: Platform Sub-study of belantamab mafodotin (GSK2857916) in 
combination with aOX40 (GSK3174998) in participants with RRMM 
Acronym: DREAMM-5 Sub-study 1 
Study Phase: Phase I/II 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Medical Director Name and Contact Information  
, MD 
 Clinical Oncology BCMA 
GSK, Oncology R&D 
1250 South Collegeville Rd 
Upper Providence, PA, 19426 
Tel: 
 
Email: 
 
Regulatory Agency Identifying Number(s):  
IND number: 136133 
EudraCT number: 2019-001138-32 
Approval Date: 14-DEC-2020 
Copyright 2020 the GlaxoSmithKline group of companies.  All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
 
PPD
PPD
PPD
PPD


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
DNG Number 
Amendment 4 (Sub-study 1) 
14-DEC-2020 
2020N453267_00 
Amendment 3 
08-JUL-2020 
2017N352487_03 
Amendment 2  
16-DEC-2019 
2017N352487_02 
Amendment 1 
24-JUN-2019 
2017N352487_01 
Original Protocol 
12-MAR-2019 
2017N352487_00 
 
Amendment 04 (Sub-study 1) 14-DEC-2020 
Overall Rationale for the Amendment:  
The 208887 protocol has been amended to convert to a modular document format with 
separate Master Protocol (MP) and sub-study modules.  The organizational changes for 
Sub-study 1 are administrative and are mapped in the table below.   
Section # for Prot-Amend 3 and Name 
Section # for Prot-Amend 4 and Name 
11.1 
Protocol Amendment 3 Summary of 
Changes Specific to Sub-study 1 
12.13.1 
Protocol Amendment 3 
11.2 
Schedule of Activities (SoA) for Belantamab 
mafodotin + GSK’998 (aOX40) 
1.3 
Schedule of Activities (SoA) 
11.3 
Background of GSK’998 (aOX40) 
(GSK3174998) 
2.2 
Background for GSK’998 (aOX40) 
(GSK3174998) 
11.4 
Rationale for combination of Belantamab 
mafodotin with GSK’998 (aOX40) 
2.1 
Rationale for combination of Belantamab 
mafodotin with GSK’998 (aOX40) 
11.5 
Dose justification for GSK’998 (aOX40) 
4.3 
Justification for Dose 
11.6 
Dose Exploration of Combination Treatment 
Belantamab mafodotin Co-Administered with 
GSK’998 (aOX40) 
4.1 
Overall Design 
11.7 
Study Interventions Administered 
6.1 
Study Intervention(s) Administered 
11.8 
Administration of Belantamab mafodotin and 
GSK’998 (aOX40) 
6.2 
Administration of Belantamab mafodotin and 
GSK’998 
11.9 
Preparation/Handling/Storage/Accountability 
6.3 
Preparation/Handling/Storage/Accountability 
– content deleted as it was identical to the 
208887 MP 
11.10 
Adverse Events of Special Interest for 
GSK’998 (aOX40) 
8.3.9 
Disease-Related Events and/or Disease-
Related Outcomes Not Qualifying as SAEs 
11.11 
Benefit/Risk 
2.3 
Benefit/Risk Assessment 
11.12 
Additional Inclusion/Exclusion Criteria for 
Sub-study 1 
5.1 
Inclusion Criteria for Participants 
5.2 
Exclusion Criteria 
11.13 
Specific GSK’998 (aOX40)-Related Dose 
Reduction and Delay Guidance 
6.6 
Dose Modification 
11.13.1 
Management of Pregnancy 
8.3.7 
Management of Pregnancy 
11.14 
Protocol Amendment History for Changes 
Specific to Sub-study 1 
12.13 
Appendix 13: Protocol Amendment History 
 
 


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Changes listed in the table below are for the Sub-study 1 protocol only. Changes for 
Protocol Amendment 4 that are related to the 208887 Master Protocol and specific sub-
studies are tabulated at the beginning of each relevant Sub-study module. 
Section # and Name 
Description of Change 
Brief Rationale 
Administrative Changes 
1.1 Synopsis 
Added language to state that Sub-study 1 has 
been closed to enrollment 
Due to current data (observed lack of 
efficacy); investigators and sites 
have already been notified 
Changes in Assessments and SoAs 
1.3 Schedule of 
Activities 
Clarified FISH assessments that are to be 
completed at Screening (Table 2) based on 
availability on previous results 
In line with other protocols in the 
program. 
Clarified footnote on Single ECG at Screening 
(Table 3) 
Clarified based on prior edits 
(Protocol Amendment 03) 
Clarified language on definition of resolution of 
ophthalmic findings (to baseline instead of 
Grade 1) 
To align with GSK belantamab 
mafodotin program language 
Protocol Clarification and Alignment 
Section 12.11. 
Appendix 11: Home 
Healthcare and 
Telemedicine 
Approaches 
Heading added for this Appendix 
Added to match new Appendix 
added to the 208887 Master Protocol 
Editing, format, style changes 
Throughout 
Correction of typos and technical document 
aspects 
Minor changes with no impact on 
content 
 
 


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TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 2 
1. 
PROTOCOL SUMMARY .......................................................................................... 7 
1.1. 
Synopsis ....................................................................................................... 8 
1.2. 
Schema ........................................................................................................ 8 
1.3. 
Schedule of Activities (SoA) .......................................................................... 8 
2. 
INTRODUCTION .................................................................................................... 23 
2.1. 
Rationale for combination of Belantamab mafodotin with GSK’998 ............. 23 
2.2. 
Background for GSK’998 (GSK3174998) .................................................... 24 
2.2.1. 
Clinical pharmacology data with GSK’998 .................................... 25 
2.2.2. 
Safety Data for GSK’998 (GSK3174998) monotherapy ................ 25 
2.2.3. 
Clinical Activity of GSK’998 Monotherapy .................................... 26 
2.3. 
Benefit/Risk Assessment ............................................................................ 26 
2.3.1. 
Risk Assessment ......................................................................... 27 
2.3.2. 
Benefit Assessment ..................................................................... 29 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 29 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 29 
4. 
STUDY DESIGN .................................................................................................... 29 
4.1. 
Overall Design ............................................................................................ 29 
4.2. 
Scientific Rationale for Study Design .......................................................... 30 
4.3. 
Justification for Dose .................................................................................. 30 
4.4. 
Participant Completion and End of Study Definition .................................... 31 
4.4.1. 
Participant Completion Definitions: .............................................. 31 
4.4.2. 
Study Completion: ....................................................................... 31 
5. 
STUDY POPULATION ........................................................................................... 31 
5.1. 
Inclusion Criteria for Participants ................................................................ 32 
5.2. 
Exclusion Criteria ........................................................................................ 32 
5.3. 
Lifestyle Considerations .............................................................................. 32 
5.4. 
Screen Failures........................................................................................... 32 
6. 
STUDY INTERVENTION ........................................................................................ 32 
6.1. 
Study Intervention(s) Administered ............................................................. 33 
6.2. 
Administration of Belantamab mafodotin and GSK’998 ............................... 33 
6.3. 
Preparation/Handling/Storage/Accountability .............................................. 34 
6.4. 
Measures to Minimize Bias: Randomization and Blinding ........................... 34 
6.5. 
Concomitant Therapy.................................................................................. 34 
6.6. 
Dose Modification ....................................................................................... 34 
6.6.1. 
Permitted Dose Reductions for Belantamab Mafodotin 
when in combination with GSK’998 .............................................. 34 
6.6.2. 
Permitted Dose Modifications of GSK’998 when in 
combination with Belantamab mafodotin ...................................... 35 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
WITHDRAWAL FROM THE STUDY ...................................................................... 36 
7.1. 
Discontinuation of Study Intervention .......................................................... 36 


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7.2. 
Participant Withdrawal from the Study ........................................................ 36 
7.3. 
Lost to Follow Up ........................................................................................ 36 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 36 
8.1. 
Efficacy Assessments ................................................................................. 36 
8.2. 
Safety Assessments ................................................................................... 36 
8.3. 
Adverse Events and Serious Adverse Events ............................................. 36 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 36 
8.3.2. 
Method of Recording AE and SAE Information ............................ 36 
8.3.3. 
Method of Detecting AEs and SAEs ............................................. 36 
8.3.4. 
Follow-up of AEs and SAEs ......................................................... 36 
8.3.5. 
Reporting of Potentially Life-Threatening AEs to the GSK 
Medical Director ........................................................................... 36 
8.3.6. 
Regulatory Reporting Requirements for SAEs ............................. 36 
8.3.7. 
Management of Pregnancy .......................................................... 36 
8.3.8. 
Cardiovascular and Death Events ................................................ 37 
8.3.9. 
Disease-Related Events and/or Disease-Related 
Outcomes Not Qualifying as SAEs............................................... 37 
8.3.10. 
Adverse Events of Special Interest .............................................. 37 
8.4. 
Treatment of Overdose ............................................................................... 38 
8.5. 
Pharmacokinetics ....................................................................................... 39 
8.6. 
Genetics ..................................................................................................... 39 
8.7. 
Immunogenicity Assessments ..................................................................... 39 
8.8. 
Biomarkers ................................................................................................. 39 
8.9. 
Health-Related Quality of Life ..................................................................... 39 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 39 
9.1. 
Statistical Hypotheses................................................................................. 39 
9.2. 
Sample Size Determination ........................................................................ 39 
9.3. 
Populations for Analyses ............................................................................ 39 
9.4. 
Statistical Analyses ..................................................................................... 39 
9.5. 
Interim Analysis .......................................................................................... 39 
9.6. 
Sample Size Sensitivity ............................................................................... 39 
10. REFERENCES ....................................................................................................... 40 
11. GUIDELINES FOR DOSE MODIFICATION AND OTHER PARTNER 
COMBINATION TREATMENTS FOR ALL SUBSTUDIES ...................................... 41 
12. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 41 
12.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 41 
12.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 41 
12.3. 
Appendix 3: AEs: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................... 41 
12.4. 
Appendix 4: ECOG Performance Status ..................................................... 41 
12.5. 
Appendix 5: NYHA Functional Classification System .................................. 41 
12.6. 
Appendix 6: Modified Diet in Renal Disease ............................................... 41 
12.7. 
Appendix 7: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................. 41 


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12.8. 
Appendix 8: Genetics .................................................................................. 41 
12.9. 
Appendix 9: Liver Safety: Required Actions and Follow-up 
Assessments and Study Treatment Rechallenge Guidelines ...................... 41 
12.10. Appendix 10: Eye Care Specialist- Qualifications and Requirements .......... 41 
12.11. Appendix 11: Home Healthcare and Telemedicine Approaches .................. 41 
12.12. Appendix 12: Abbreviations and Trademarks .............................................. 42 
12.13. Appendix 13: Protocol Amendment History ................................................. 45 
 


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1. 
PROTOCOL SUMMARY 
Please refer to the 208887 Master Protocol (MP) for the overall Protocol Summary for 
the study. 
Information and details specific to Sub-study 1 are in the subsections below.  These are 
summarized in Table 1.  Please refer to the 208887 MP for other sections and content. 
Table 1 
Location of Sub-study 1-specific Content 
Section 
Heading title 
Brief description of content 
1.3 
Schedules of Activities 
Comprehensive SoA tables specific for Sub-study 1 
2.1 
Rationale for combination of 
Belantamab mafodotin with 
GSK’998 (aOX40) 
Explanation why treatment with belantamab 
mafodotin and aOX40 is expected to be 
complementary 
2.2 
Background for GSK’998 
(aOX40) (GSK3174998) 
Available data on clinical pharmacology, safety and 
clinical activity 
2.3 
Benefit/Risk Assessment 
Risk assessments for aOX40 treatment; benefit 
assessment summary 
4.1 
Dose Exploration of 
Combination Treatment 
Belantamab mafodotin Co-
Administered with GSK’998 
(aOX40) 
Description of dose escalation design for the 
combination treatment  
4.3 
Dose justification for GSK’998 
(aOX40) 
Data for the basis of the planned aOX40 dosing 
5.2 
Exclusion Criteria 
Two additional exclusion criteria were defined for 
Sub-study 1 
6.1 
Study Intervention(s) 
Administered 
Specifications for belantamab mafodotin and aOX40 
IP 
6.2 
Administration of Belantamab 
mafodotin and aOX40 
Specifications for administration of belantamab 
mafodotin and aOX40 
6.6 
Dose Modification for 
Belantamab Mafodotin When 
in Combination with GSK’998 
Detailed directions guidance for dose modifications 
of combination treatment 
8.3.7 
Management of Pregnancy 
Timeframes for on data collection 
8.3.9 
Disease-Related Events 
and/or Disease-Related 
Outcomes Not Qualifying as 
SAEs 
Information on aOX40 AESI 
8.4 
Treatment of Overdose of 
aOX40 (GSK3174998) 
Guidance for potential drug overdose of aOX40 
12.13 
Appendix 13: Protocol 
Amendment History 
Summary of Changes Tables for Sub-study 1 
specific amendments 
 


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1.1. 
Synopsis 
Enhanced antigen presentation through ICD and resulting T cell-mediated durable 
immunity, suggests that additional therapeutic benefit can be obtained from combination 
treatment of belantamab mafodotin with immune-enhancing agents such as GSK’998 
(aOX40).  Murine aOX40 (OX86) in combination with belantamab mafodotin provided 
with survival benefit in mice over GSK’916 single agent activity, although, it did not 
reach statistical significance.  In addition, the combination of OX86 at 0.2, 1 and 5 mg/kg 
with belantamab mafodotin resulted in 7, 4 and 5 (out of 10 mice) tumor free survivors. 
This is a randomized Phase I/II, open-label, platform-design study of belantamab 
mafodotin in combination with GSK’998 (aOX40) treatment compared to belantamab 
mafodotin monotherapy in participants with RRMM.  Overall design is in relation to the 
dose exploration of combination treatment. 
There will be a dose exploration (DE) phase which will evaluate the safety and 
tolerability profile of belantamab mafodotin when administered in combination with 
other anti-cancer treatments. The number of dose levels explored will vary per sub-study, 
and up to 10 participants per dose level will evaluated for safety and preliminary efficacy. 
A recommended Phase 2 dose (RP2D) for each combination treatment will be identified 
based on the safety and preliminary efficacy in DE. This will be followed by a cohort 
expansion (CE) phase which will evaluate the clinical activity of the combination 
treatment in comparison to monotherapy belantamab mafodotin in additional participants 
with RRMM at the RP2D in sub-studies.   
A total of 3 dose levels can be potentially evaluated, so there could potentially be a 
maximum of 3 dosing cohorts running simultaneously in the dose exploration (DE) 
phase.  The starting dose of belantamab mafodotin will be 1.9 mg/kg and the starting 
dose of GSK’998 (aOX40) will be 8 mg every 3 weeks.  Please see 208887 MP Section 
4.1.1 for details of decision making during the DE phase. 
Sub-study 1 has been closed to enrollment. 
1.2. 
Schema 
1.3. 
Schedule of Activities (SoA) 
• The timing and number of planned study assessments, including [safety, 
pharmacokinetic, ADA, biomarker or others] assessments may be altered during 
the course of the study based on newly available data (e.g., to obtain data closer to 
the time of peak plasma concentrations) to ensure appropriate monitoring.  
• Note: belantamab mafodotin is referred to as GSK’916 only for the purposes of 
Laboratory assessments and samples. 
• Note: GSK’998 (aOX40) is referred to as GSK’998 only for the purposes of 
Laboratory assessments and samples 
 


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Table 2 
SoA – Screening for DE and CE Phases: Belantamab Mafodotin and GSK’988 (aOX40) 
Screening Study Assessments 
Screening 
Notes 
Note: All Screening assessments must be performed within 30 days prior to Cycle 1 Day 1 (C1D1) unless otherwise specified. Informed Consent must be signed before any study-
specific assessments are performed. Screening Assessment do not need to be repeated on C1D1 unless otherwise specified.  All other assessments can be done ≤3 days prior to 
treatment unless otherwise specified. 
Informed Consent 
X 
1. 
Screening/baseline ocular examination will be performed by a qualified eye-care specialist 
(ophthalmologist/optometrist) within 30 days prior to C1D1 (see 208887 MP Section 8.2.7 for list of 
ophthalmic exam procedures). Screening assessment does not need to be repeated on C1D1 unless 
otherwise specified. (see 208887 MP Section 8.2.7 for list of ophthalmic exam procedures). 
2. 
Perform only in women of child-bearing potential. Two serum pregnancy tests should be performed at 
screening.  The first test should be performed at least 10 days prior to C1D1 and the second test 
within 72 hours prior to administration of C1D1.   
3. 
Refer to 208887 MP Appendix 2 for a comprehensive list of lab tests that must be collected for all 
participants. 
4. 
TSH, free T3 and T4. 
5. 
eGFR as calculated by Modified Diet in Renal Disease (MDRD) formula (208887 MP Appendix 6). 
6. 
Urine dipstick for protein may be used to assess for presence of urine protein. Albumin/creatinine ratio 
needs to be done in any participant with urine dipstick result of ≥1+ at screening, or with positive 
protein if urine dipstick protein quantification is not available. Albumin/creatinine will be performed at a 
local lab.(first void). 
7. 
Complete at screening or within 12 weeks prior to C1D1.  
8. 
Hep C RNA testing is optional, but it may be performed to determine participant eligibility if Hep C 
antibody positive. If negative, patient is eligible (see exclusion criteria 12 for details). 
9. 
Single ECG at Screening. 
10. ECHO may be performed within 30 days C1D1. 
11. SPEP and UPEP will include M protein calculations. 
12. Serum Free Light Chain assay will include kappa/lambda ratio and quantification of involved and 
uninvolved light chains. 
13. IgD/IgE testing is only required for patients with IgD/IgE myeloma.  
14. Skeletal Survey: Imaging of bones for lytic lesions by a method aligned with the institutional guidance 
(X-ray, CT, or MRI). X-Ray is acceptable for lytic disease, but other methods are needed (CT, MRI, 
PET/CT) for assessment of extramedullary disease. Skeletal survey results within 30 days prior to 
C1D1 may be used for screening. Same modality used at Screening should be used throughout study. 
15. In participants with known or suspected extramedullary plasmacytoma, a whole-body scan (i.e., CT, 
MRI, or PET-CT) should be performed within 30 days prior to C1D1.  The same method should be 
Demography 
X 
Medical History (includes substance abuse) 
X 
Full Physical Exam 
X 
Throughout the trial, participants are 
educated about in life style considerations 
(208887 MP Section 5.3) for the study and 
the need of maintaining adequate urinary 
output (208887 Section 2.3.1). 
X 
Inclusion/Exclusion criteria  
X 
Past and current medical conditions 
X 
Concomitant Medication review  
X 
Screening Safety Assessments 
 
Ocular Exam 
X1 
ECOG Performance Status  
X 
Vital Signs (BP, HR, Body Temperature) 
X 
Weight and Height 
X 
Serum Pregnancy Test (WOCBP only) 
X2 
Hematology (CBC) 
X3 
Clinical chemistry  
X3 
Thyroid Function Tests 
X4 
Estimated Glomerular Filtration (eGFR) 
X5 
Urinalysis (dipstick) OR Spot Urine 
(albumin/creatinine ratio) 
X6 
HBsAg, HBcAb, HCV8 tests 
X7 
12-lead ECG 
X9 
ECHO LVEF 
X10 
Screening Disease Evaluation 
 


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Screening Study Assessments 
Screening 
Notes 
Note: All Screening assessments must be performed within 30 days prior to Cycle 1 Day 1 (C1D1) unless otherwise specified. Informed Consent must be signed before any study-
specific assessments are performed. Screening Assessment do not need to be repeated on C1D1 unless otherwise specified.  All other assessments can be done ≤3 days prior to 
treatment unless otherwise specified. 
Beta2 microglobulin 
X 
used throughout the study (i.e., if a PET-CT scan was used as baseline scan than participants needs 
to be followed by PET-CT scans).  Selected target lesion needs to be measured and followed over 
time.  Whole body MRI is also acceptable, as long as it is able to be repeated over the duration of the 
study until confirmed disease progression. Note: Germany: no PET/CT to confirm CR or sCR will be 
performed until approval by the German Federal Office for Radiation Protection. 
16. Immunohistochemistry (IHC) of bone marrow core biopsy is preferred for quantitative assessment of 
malignant plasma cells.  However, bone marrow aspirate is acceptable and should be performed 
within 60 days of C1D1.  Archival tissue from up to 60 days prior to C1D1 is acceptable. 
17. FISH testing at least for: t(4;14), t(14;16), amp(1q), del(1p), del(17p13). ). If participant is known to 
have tested positive for t(4;14) or t(14/16) on previous tests, FISH for those translocations does not 
need to be repeated, but results from previous tests are acceptable regardless of when those tests 
were performed. For amp(1q), del(1p) and del(17p13), FISH results from samples taken within 60 
days prior to C1D1 are acceptable. 
18. These assessments will be performed by a central laboratory.  
19. Minimal residual disease (MRD) testing to be performed by the central lab at screening, at the time of 
first achieving VGPR or CR. Repeat MRD testing every 6 months after achieving VGPR or CR 
(provided VGPR/CR is maintained). 
 
 
UPEP 24 hr urine collection 
X11 
Urine immunofixation 
X11 
SPEP 
X11 
Serum Immunofixation 
X 
Serum FLC assay 
X12 
IgG, IgM, IgA 
X 
IgD or IgE, if applicable 
X13 
Calcium corrected for albumin (serum) 
X 
Skeletal Survey 
X14 
Extramedullary Plasmacytoma Assessment 
(by whole body CT or whole body MRI or 
CT/PET) 
X15 
Bone Marrow (BM) Aspiration/Biopsy 
 
BM (biopsy and/or aspirate) for local disease 
assessment  
X16 
BM aspirate for local FISH testing  
X17 
BM aspirate for BCMA expression and 
immune cell characterization/profiling  
X18 
BM aspirate for MRD testing 
X18,19 
ADA = Anti-drug Antibody; ALP = alkaline phosphatase; NT-proBNP = N-terminal pro B-type natriuretic peptide; D1 = Day 1, etc.; CBC Complete Blood Count, cfDNA = Circulating free DNA; CK = 
creatinine kinase; CT = computed tomography; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; EM = extramedullary;  EOI = End of Infusion; FISH = Fluorescence in situ 
hybridization; FLC = free light chain; IgD/IgE = Immunoglobulin D or E; LVEF = left ventricular ejection fraction; MRI = magnetic resonance imaging; PET = positron emission tomography; PFS = 
progression-free survival; PD = progressive disease; PK = pharmacokinetics; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis. 
 


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Table 3 
SoA – Treatment Period for DE and CE Phases: Belantamab mafodotin and GSK’988 (aOX40) Study Assessments 
to be carried every 3 weeks regardless of whether participant is dosed 
Study Assessments 
regardless of whether 
participant is dosed 
Day 1 
(Week 1) 
 
Treatment Period: Q3W 
from Week 4 until EoT 
Notes 
Note: All assessments will apply to both the DE and CE Phases unless stated otherwise. Assessments scheduled on days of dosing should be done prior to drug administration, 
unless otherwise specified.  All assessments from Week 4 can be performed ≤3 days prior to the scheduled date unless otherwise specified. 
Adverse Events 
Ongoing1  
1. 
AEs/SAEs will be collected up to 70 days after the last dose of study treatment and 
immune-related AEs/SAEs will be collected up to 90 days post last dose.  All SAEs 
related to study participation (e.g., protocol mandated procedures, tests, or change 
in existing therapy) are to be collected from consent through OS follow-up. All 
AE’s/SAE’s will be followed until the event is resolved, stabilized, otherwise 
explained, or the participant is lost t follow-up. 
2. 
Informed consent for optional sub studies (e.g. genetic research) must be obtained 
before collecting a sample. The sample will be collected on C1D1 prior to infusion. 
3. On-study ocular exams to be performed by a qualified eye-care specialist Q3W prior 
to dosing up to the sixth dose of belantamab mafodotin (assessment window up to 
5 days prior to dosing, but all effort should be made to schedule as close to 
belantamab mafodotin dosing as possible). See 208887 MP Section 8.2.7 for list of 
ophthalmic exam procedures. If there are no significant ocular examination findings, 
change in patient symptoms or vision at the time of the sixth dose exam, participants 
may have their ophthalmologic exams decreased to once every 3 months. If a 
participant subsequently develops vision changes or other ocular symptoms, the 
participant should be promptly evaluated by a qualified eye care specialist. In case of 
persistent ophthalmic exam findings, newly developed ocular symptoms or vision 
changes, the participants will have further ophthalmologic exams at least every cycle 
until resolution (to baseline), or more frequently as clinically indicated by the qualified 
eye care specialist.    
4. 
If completed within 72 hrs prior to the dose, this assessment does not need to be 
repeated on Day 1 of Cycle 1. Day 8 Cycles 1-6 only and Day 15 Cycles 1 and 2 
only. CBC may be done more frequently as clinically indicated. Refer to 208887 MP 
Appendix 2 for comprehensive list of lab tests. 
5. 
eGFR every dose as calculated by Modified Diet in Renal Disease (MDRD) formula 
(208887 MP Appendix 6). 
Concomitant 
Medications 
Ongoing 
Throughout the trial, 
participants are 
educated about in life 
style considerations 
(208887 MP Section 5.3) 
for the study and the 
need of maintaining 
adequate urinary output 
(208887 MP Section 
2.3.1). 
X 
Genetics 
X2 
 
 
ECOG Performance 
Status  
 
 
X 
Safety 
Ocular Exam 
 
 
X3 
Hematology (CBC) 
X4 
 
X4 
Clinical chemistry  
X4 
 
X4 
eGFR 
X5 
 
X5 
Urinalysis (dipstick) OR 
Spot Urine 
(albumin/creatinine ratio) 
X6 
 
X6 
ECHO 
 
 
X7 
Disease Evaluation (every 3 weeks even if a dose is delayed) 
UPEP 24 hr urine 
collection  
 
 
X 


2020N453267_00 
CONFIDENTIAL 
 
 
 
208887 Sub-study 1 
 
12 
 
Study Assessments 
regardless of whether 
participant is dosed 
Day 1 
(Week 1) 
 
Treatment Period: Q3W 
from Week 4 until EoT 
Notes 
Note: All assessments will apply to both the DE and CE Phases unless stated otherwise. Assessments scheduled on days of dosing should be done prior to drug administration, 
unless otherwise specified.  All assessments from Week 4 can be performed ≤3 days prior to the scheduled date unless otherwise specified. 
Urine immunofixation 
 
 
X8 
6. 
Urine dipstick for protein may be used to assess for presence of urine protein. 
Albumin/creatinine ratio needs to be done in any participant with urine dipstick result 
of ≥2+, or with positive protein if urine dipstick protein quantification is not available. 
Albumin/creatinine will be performed at a local lab be performed (first void). 
7. 
ECHOs to be done if clinically indicated.  
8. 
At time of first achieving serum and urine M protein ~ 0g/dl (suspected CR) and until 
suspected PD after CR or sCR. 
SPEP 
 
 
X 
Serum Immunofixation 
 
 
X8 
Serum FLC assay 
 
 
X9,10 
IgG, IgM, IgA 
 
 
X 
9. 
Every 3 weeks and at time of sCR assessment. 
10. Serum Free Light Chain assay will include kappa/lambda ratio and quantification of 
involved and uninvolved light chains. 
11. IgD/IgE testing is only required for participants with IgD/IgE myeloma.   
12. Skeletal Survey (at the time of suspected disease progression or as clinicall 
indicated): Imaging of bones for lytic lesions by a method aligned with the 
institutional guidance (X-ray, CT, or MRI). X-Ray is acceptable for lytic disease, but 
other methods are needed (CT, MRI, PET/CT) for assessment of extramedullary 
disease. Same modality used at Screening should be used throughout study. 
13. As clinically indicated, or to confirm PD. To be performed by the same method 
throughout the study as was done at baseline (i.e. if CT/PET scan was used as 
baseline, participant needs to be followed by CT/PET scans).  Selected target lesion 
needs to be measured and followed over time (every 12 weeks). 
14. Note: Germany: no PET/CT to confirm CR or sCR will be performed until approval 
by the German Federal Office for Radiation Protection. 
15. Bone marrow aspirate sample should be collected at time of Progressive Disease. 
Central laboratory assessment.  
16. Optional bone marrow aspirate samples to be collected at one of the following 
timepoints: C1D8 or C1D15 during any 3 week period for biomarker assessments 
and, if possible as part of the same BM draw whenever MRD is assessed. BM 
aspirate clot is preferred for BCMA assay.  Central laboratory assessment.  
IgD orIgE 
 
 
X11 
Calcium corrected for 
albumin (serum) 
 
 
X 
Skeletal Survey 
 
 
X12 
Extramedullary 
Plasmacytoma 
Assessment (by whole 
body CT or whole body 
MRI or CT/PET) 
 
 
X13 
MRI, CT or PET/CT 
upon achieving CR or 
sCRr 
 
 
Once after CR or sCR14 
Bone Marrow (BM) Aspiration/Biopsy 
BM aspirate for BCMA 
expression and immune 
cell 
characterization/profiling 
 
 
X15,16 
MRD testing bone 
marrow aspirate 
 
 
X17 
BM aspirate/core biopsy 
for local Disease 
assessment 
 
 
X18 


2020N453267_00 
CONFIDENTIAL 
 
 
 
208887 Sub-study 1 
 
13 
 
Study Assessments 
regardless of whether 
participant is dosed 
Day 1 
(Week 1) 
 
Treatment Period: Q3W 
from Week 4 until EoT 
Notes 
Note: All assessments will apply to both the DE and CE Phases unless stated otherwise. Assessments scheduled on days of dosing should be done prior to drug administration, 
unless otherwise specified.  All assessments from Week 4 can be performed ≤3 days prior to the scheduled date unless otherwise specified. 
BM core biopsy to 
assess sCR (local)  
 
 
X18 
17. MRD testing to be performed by a central lab at the time of first achieving VGPR or 
CR. Repeat MRD testing every 6 months after achieving VGPR or CR (provided 
VGPR/CR is maintained). 
18. At the time of suspected CR for confirmation of PC% <5% (always) or at time of 
suspected PD (only if not evident otherwise). IHC to confirm sCR on BM biopsy 
when CR is achieved.  Absence of clonal cells in BM biopsy by IHC is required to 
determine sCR. 
19. Assessed in CE Phase only. 
20. OSDI will be performed at C1D1, C4D1 and EoT only. Additional assessments may 
be conducted for those participants who are experience a worsening in visual 
function. 
21. Collected pre-dose every 6 weeks from Cycle1 until EoT. 
 
Health Outcomes19 
PRO-CTCAE 
X 
 
X 
OSDI 
X20 
 
X20 
EORTC-QLQ-C30, and 
EORTC-QLQ-IL52 
X21 
 
X21 
ADA = Anti-drug Antibody; ALP = alkaline phosphatase; D1 = Day 1, etc.; cfDNA = Circulating free DNA; CK = creatinine kinase; CT = computed tomography; ECG = 
electrocardiogram; eGFR = estimated glomerular filtration rate; EM = extramedullary;  EOI = End of Infusion; EORTC QLQ-C30 = European Organisation for Research and Treatment 
of Cancer Quality of Life Questionnaire 30-item Core module; EORTC QLQ-IL52 = European Organisation for Research and Treatment of Cancer Item Library 52; FLC = free light 
chain; IgE/D = Immunoglobulin E/D; LVEF = left ventricular ejection fraction; MRI = magnetic resonance imaging; OSDI = Ocular Surface Disease Index; PET = positron emission 
tomography; PFS = progression-free survival; PRO-CTCAE = Patient Reported Outcome version of the Common Term Criteria for Adverse Events; PD = progressive disease; PK = 
pharmacokinetics; RRMM = relapsed/refractory MM; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis 
 


2020N453267_00 
CONFIDENTIAL 
 
 
 
208887 Sub-study 1 
 
14 
 
Table 4 
SoA – Treatment Period on Dosing Days or After Dosing Only: regarding Belantamab mafodotin and GSK’998 
(aOX40) 
Study Assessments 
Cycle 1 
Day 1 
(Week 1) 
Day 4 (±1 
day) 
(Cycle 1) 
 
Cycle 1 
Day 8 
(Cycles 
1-6) 
Day 15 
(Cycles1 
& 2 only) 
(Week 2) 
Day 1 of Cycle 2 
– last 
Cycle/participant 
 
Notes 
All assessments will apply to both the DE and CE Phases unless stated otherwise. Assessments should be done prior to drug administration, unless otherwise specified.  From 
Dose 2, assessments can be performed ≤3 days prior to the scheduled date unless otherwise specified. 
Safety 
1. 
Vital signs must be assessed for each infusion belantamab mafodotin at: pre-dose (within 
30 minutes prior to SOI); post each infusion (EOI); and 1 hour post EOI. Measured after 
resting for at least 5 minutes. For first infusion, must be monitored at pre-dose (within 30 
minutes prior to start of each infusion), and at the end of each infusion, and 1 hour post 
end of infusions. For subsequent infusions, vital signs must be monitored at pre-dose 
(within 30 minutes prior to start of each infusion) and at the end of each infusion, and 30 
min post the end of infusion. On dosing days with PK sampling time points, vital signs 
should be assessed prior to PK samples being drawn. Single vital sign assessment 
measured after resting for at least 5 minutes required on Day 8 (Dose1-6) and Day 15 
(Doses 1&2). 
2. 
Perform only in women of child-bearing potential.  Pregnancy tests may be either pre-
dose serum or urine and should be performed within 72 hours prior to each dose.  
3. 
Only if clinically indicated, at the local lab (troponin I or T) and a central lab if required 
(troponin I).   
4. 
Urine dipstick for protein may be used to assess for presence of urine protein. 
Albumin/creatinine ratio needs to be done in any participant with urine dipstick result of 
≥2+, or with positive protein if urine dipstick protein quantification is not available. 
Albumin/creatinine will be performed at a local lab (first void). 
5. 
If completed within 72 hours prior to the dose, this assessment does not need to be 
repeated on Day 1 of each Cycle. Day 8 Cycles1-6 only and Day 15 Cycles 1 and 2 only 
Physical Exam (Full 
exam on treatment 
days Day 1 of each 
cycle, and D8 Cycle 1 
only) 
X 
 
X 
X 
Vital Signs (BP, HR, 
Body Temperature) 
X1 
X1 
X1 
X1 
Weight 
X 
 
X 
X 
ECOG Performance 
Status 
X 
 
 
X 
Pregnancy Test  
X2 
 
 
X2 
Troponin 
 
 
 
X3 
Urinalysis (dipstick) 
OR Spot Urine 
(albumin/creatinine 
ratio) 
X4 
 
 
X4 
Hematology (CBC) 
X5 
 
X5 
X5 
Clinical chemistry  
X5 
 
X5 
X5 
eGFR 
X6 
 
X6 
X6 


2020N453267_00 
CONFIDENTIAL 
 
 
 
208887 Sub-study 1 
 
15 
 
Study Assessments 
Cycle 1 
Day 1 
(Week 1) 
Day 4 (±1 
day) 
(Cycle 1) 
 
Cycle 1 
Day 8 
(Cycles 
1-6) 
Day 15 
(Cycles1 
& 2 only) 
(Week 2) 
Day 1 of Cycle 2 
– last 
Cycle/participant 
 
Notes 
Thyroid Function 
Tests 
X7 
 
 
X7 
CBC may be done more frequently as clinically indicated. Refer to Appendix 2 for 
comprehensive list.  
6. 
eGFR as calculated by Modified Diet in Renal Disease (MDRD) formula (208887 MP 
Appendix 6). 
7. 
Every 6 weeks while on GSK’998 therapy: TSH, free T3 and free T4. 
8. 
PK samples to be taken in all participants for GSK’998: Dose1 D1 - predose anytime prior 
to GSK’916 SOI, GSK’998 EOI (0 – 5 min after EOI), 2-4 h after GSK’998 SOI, 24 hr 
(±2h) after SOI; Dose1 D4 – anytime; Dose1 D8 – anytime;  Not required on Dose 1 Day 
15; Dose2 D1 – predose anytime prior to GSK’916 SOI (or Dose1 D22 if Dose 2 is 
delayed) and GSK’998 EOI (0 – 5 min after EOI); Doses 4, 6, 9, and 12 - predose (prior 
to GSK’916 SOI) and GSK’998 EOI (0 – 5 min after EOI);  every 6 doses thereafter  - 
predose (prior to GSK’916 SOI). 
9. 
ADA serum samples will be collected predose (within 30 min prior to GSK’916 SOI) at: 
Doses 1, 2, 4, 6, 9, 12 and every 6 does thereafter.  
10. PK samples to be taken in all participants for GSK’916: Dose1 D1 - predose (within 30 
minutes prior to GSK’916 SOI), EOI (0 – 5 min after GSK’916 EOI); at Dose 1 2 hours 
(±15 min) after GSK’916 SOI; Dose 1 24 hours (±2 hours) after GSK’916 SOI; Dose1 D4 
- anytime, Dose1 D8 – anytime;  Not required on Dose 1 Day 15;  Dose 2 D1 – predose 
(within 30 min prior to GSK’916 or Dose1 D22 if Dose 2 is delayed); Dose 2 D1 EOI (0 – 
5 min after GSK’916  EOI); Doses 4, 6, 9, and 12 - predose (within 30 minutes prior to 
GSK’916 SOI) and EOI (0 – 5 min after GSK’916 EOI);  every 6 doses thereafter  - 
predose (within 30 minutes prior to GSK’916 SOI). 
PK and ADA 
Plasma PK for 
GSK’998  
X8 
X8 
X8 
X8 
Serum 
immunogenicity (ADA) 
for GSK’998  
X9 
 
 
X9 
Plasma PK GSK’916  
X10 
X10 
X10 
X10 
Serum 
Immunogenicity (ADA) 
for GSK’916  
X9 
 
 
X9 
Biomarkers 
Serum (soluble 
BCMA) for GSK’916  
X11 
 
X11 
X11 
Plasma-cfDNA  
X12 
 
 
 
Cytokines/chemokines 
X13 
 
X13 
X13 


2020N453267_00 
CONFIDENTIAL 
 
 
 
208887 Sub-study 1 
 
16 
 
Study Assessments 
Cycle 1 
Day 1 
(Week 1) 
Day 4 (±1 
day) 
(Cycle 1) 
 
Cycle 1 
Day 8 
(Cycles 
1-6) 
Day 15 
(Cycles1 
& 2 only) 
(Week 2) 
Day 1 of Cycle 2 
– last 
Cycle/participant 
 
Notes 
Whole blood RNA 
X14 
 
X14 
 
11. Collect a sBCMA serum sample every time a GSK’916 PK sample is collected and at 
additional timepoints, as indicated: at Dose 1 D1 predose (within 30 minutes prior to 
GSK’916 SOI), EOI (0 – 5 min after GSK’916 EOI), at 2 hours (±15 min) and 24 hours 
(±2 hours) after GSK’916 SOI, Dose1 D4 – anytime, Dose 1 D8 – anytime, Dose 1 D15 - 
anytime, Dose 2 D1 – predose GSK’916 (within 30 minutes prior to SOI or Dose1 D22 if 
Dose 2 is delayed), Dose 2 D1 EOI (0 – 5 min after GSK’916 EOI); Doses 4, 6, 9, and 12 
- predose (within 30 minutes prior to GSK’916 SOI) and EOI (0 – 5 min after GSK’916 
EOI); every 6 doses thereafter predose (within 30 minutes prior to GSK’916 SOI). Also 
collect sBCMA at every MRD assessment and at EoT.    
12. Plasma cfDNA samples should be collected prior to the first GSK’916 infusion, at Dose 1 
D1, every 12 weeks thereafter, at the end of treatment, and at every MRD assessment 
timepoint, regardless of dosing. 
13. To be collected at Dose 1 predose, Dose 1 - 4 hours (±30 min after EOI), Dose 1 - D8 
anytime, Dose 1 Day 15 – anytime and Dose 2 and Dose 4 predose. 
14. Relevant to GSK’916 and sub-study combination treatments. Collection (Pax gene tube) 
at Dose 1 Day 1 predose, Dose 1 Day 8 – anytime, Dose 1 Day 15 – anytime, and Dose 
2 Day 1 and Dose 4 Day 1- predose. 
15. Relevant to GSK’916 and sub-study combination treatments. Collection at Dose 1 Day 1 
predose, Dose 1 - 4 hours (±30 min after EOI), Dose 1 Day 8 – anytime Dose 1 Day 15 – 
anytime, and Dose 2 Day 1 and Dose 4 Day 1 - predose. 
16. Collect prior to GSK’916 infusion at Dose 1 D1, Dose 2 D1, Dose 3 D1, at first MRD 
assessment, and at EoT.  
17. Please refer to 208887 MP Section 6.6.3 and Section 6.6 of the protocol for guidance on 
dose delays, reduction and modification. The next scheduled dose must be administered 
every 21 days (+3-day window) since last dose. If in the judgment of the investigator, 
Cryopreserved 
PBMCs 
X15 
 
X15 
 
Peripheral blood for 
CMMC analysis 
X16 
 
 
X16 
Treatment with Belantamab mafodotin 
Administration of 
belantamab mafodotin 
X 
 
 
Day 1 of each 
dose17 


2020N453267_00 
CONFIDENTIAL 
 
 
 
208887 Sub-study 1 
 
17 
 
Study Assessments 
Cycle 1 
Day 1 
(Week 1) 
Day 4 (±1 
day) 
(Cycle 1) 
 
Cycle 1 
Day 8 
(Cycles 
1-6) 
Day 15 
(Cycles1 
& 2 only) 
(Week 2) 
Day 1 of Cycle 2 
– last 
Cycle/participant 
 
Notes 
Premedication if 
needed 
- 
 
 
X (at the start of 
each dose)18 
treatment needs to be initiated prior to the next planned scheduled dose, in cases where 
clinical toxicity has resolved, please discuss with the Medical Director. All assessments 
should remain on schedule with the exception of those associated with dosing. 
Belantamab mafodotin will be administered as an IV infusion (see Section 6.1 for details).  
18. Premedication should be considered in any participant who experienced an infusion 
related reaction at first or any subsequent infusion with belantamab mafodotin or partner 
combination see relevant sub-study Section 6.2. 
19. Supportive care information:  
a. 
Prophylactic preservative-free artificial tears should be administered in each eye at 
least 4-8 times daily beginning on Dose 1 Day 1 until end of treatment. In the event 
of ocular symptoms (e.g., dry eyes), the use of artificial tears may be increased up to 
every 2 hours as needed. Corticosteroid eye drops are not required but can be used 
if clinically indicted per the discretion of the eye-care specialist. Allow at least 5-10 
minutes between administration of artificial tears and steroid eye drops (if 
administered). 
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. 
c. 
For participants with history of dry eyes, or participants who develop dry eye during 
study treatment, the eye-care specialist should consider use of additional 
products/treatments as per local institutional guidance.  
20. Administration to occur at least 1 hour after administration of belantamab mafodotin. 
 
Treatment prophylaxis 
and management of 
preservative-free 
artificial tears and 
cooling masks 
X19 
 
 
X19 
Treatment with GSK’998 (aOX40) 
Administration of 
GSK’998 (aOX40) 
X 
 
 
Day 1 of each 21-
day cycle20 
 
ADA = Anti-drug Antibody; ALP = alkaline phosphatase; D1 = Day 1, etc.; cfDNA = Circulating free DNA; CK = creatinine kinase; CT = computed tomography; ECG = 
electrocardiogram; eGFR = estimated glomerular filtration rate; EM = extramedullary;  EOI = End of Infusion; EORTC QLQ-C30 = European Organisation for Research and Treatment 
of Cancer Quality of Life Questionnaire 30-item Core module; EORTC IL52 = European Organisation for Research and Treatment of Cancer Item Library 52; FLC = free light chain; 
IgE/D = Immunoglobulin E/D; LVEF = left ventricular ejection fraction; MRI = magnetic resonance imaging; OSDI = Ocular Surface Disease Index; PET = positron emission 


2020N453267_00 
CONFIDENTIAL 
 
 
 
208887 Sub-study 1 
 
18 
 
tomography; PFS = progression-free survival; PRO-CTCAE = Patient Reported Outcome version of the Common Term Criteria for Adverse Events; PD = progressive disease; PK = 
pharmacokinetics; QID = 4 times a day; RRMM = relapsed/refractory MM; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis 
 


2020N453267_00 
CONFIDENTIAL 
 
 
 
208887 Sub-study 1  
 
19 
 
Table 5 
SoA: End of Treatment (EoT) and Follow-up for Sub-study 1: Belantamab mafodotin and GSK’998 (aOX40) 
Study Assessments 
End of  
Treatment 
Visit1 
 
PFS Follow-
up2 
OS 
Follow-
up3 
Notes 
All assessments will apply to both the DE and CE Phases unless stated otherwise. 
Physical Exam 
X 
 
X 
 
1. 
EoT visit safety assessments to occur within 30 days from the last dose, or prior 
to the new anti-MM treatment (whichever occurs first). 
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. Once participant progresses, move to OS Follow-
up. 
3. 
The survival for MM will be documented in medical charts. No visit necessary. 
Contacts will be made via phone calls, emails or other means of communications 
every 12 weeks (±14 days) until end of study.  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. 
AEs/SAEs will be collected up to 70 days after the last dose of study treatment 
and immune-related AEs/SAEs will be collected up to 90 days post last dose.  All 
SAEs related to study participation (e.g., protocol mandated procedures, tests, or 
change in existing therapy) are to be collected from consent through OS follow-
up. All AE’s/SAE’s will be followed until the event is resolved, stabilized, 
otherwise explained, or the participant is lost to follow-up. 
5. 
End of treatment ophthalmic exam to be performed by a qualified eye-care 
specialist. See 208887 MP Section 8.2.7 for list of exams. 
6. 
Participants with a treatment-related change in vision at the End of Treatment 
Visit will be followed every 6 weeks (±7 days) until return to baseline, deemed 
clinically stable by the eye-care specialist, or up to 12 months (whichever comes 
first). Clinically stable is defined as changes ≤Grade 1.  See 208887 MP Section 
8.2.7 for list of exams 
7. 
CBC may be done more frequently as clinically indicated. Refer to 208887 MP 
Appendix 2 for comprehensive list of lab tests. 
8. 
Final pregnancy test (serum or urine) must be performed in women of 
childbearing potential 90 days (±7 days) after last dose of study treatment. For 
Vital Signs (BP, HR, Body 
Temperature) 
X 
 
X 
 
Adverse Events 
X4 
 
Related 
SAEs only4 
Related 
SAEs 
only4 
Concomitant Medications 
X 
 
X 
 
Safety 
Ocular Exam 
X5 
 
X6 
X6 
ECOG Performance 
Status  
X 
 
X 
 
Hematology (CBC) 
X7 
 
X7 
 
Clinical chemistry  
X7 
 
X7 
 
Pregnancy Test  
X8 
 
X8 
X8 
eGFR 
X9 
 
 
 
Urinalysis (dipstick) OR 
Spot Urine 
(albumin/creatinine ratio) 
X10 
 
 
 
ECHO 
X11 
 
 
 
Disease Evaluation every 3 weeks 
UPEP 24 hr urine 
collection  
X 
 
X 
 
Urine immunofixation 
X12 
 
X12 
 
SPEP 
X 
 
X 
 
Serum Immunofixation 
X12 
 
X12 
 
Serum FLC assay 
X 
 
X 
 


2020N453267_00 
CONFIDENTIAL 
 
 
 
208887 Sub-study 1  
 
20 
 
Study Assessments 
End of  
Treatment 
Visit1 
 
PFS Follow-
up2 
OS 
Follow-
up3 
Notes 
All assessments will apply to both the DE and CE Phases unless stated otherwise. 
IgG, IgM, IgA 
X 
 
X 
 
questionable cases Follicle Stimulating Hormone (FSH) and estradiol (as needed 
in women of non-child bearing potential only). A follow up pregnancy assessment 
by telephone (for WOCBP only) should be performed 8 months after the last 
dose of study treatment. 
9. 
eGFR as calculated by Modified Diet in Renal Disease (MDRD) formula (208887 
MP Appendix 6). 
10. Urine dipstick for protein may be used to assess for presence of urine protein. 
Albumin/creatinine ratio needs to be done in any participant with urine dipstick 
result of ≥2+, or with positive protein if urine dipstick protein quantification is not 
available. Albumin/creatinine will be performed at a local lab (first void). 
11. ECHO only done as clinically indicated. 
12. At time of first achieving SPEP and UPEP M protein ~ 0g/dl (suspected CR) and 
until suspected PD after CR or sCR. 
13. IgD/IgE testing is only required for patients with IgD or IgE myeloma.  
14. Imaging of bones for lytic lesions by a method aligned with the institutional 
guidance (X-ray, CT, or MRI). X-Ray is acceptable for lytic disease. 
15. At the time of suspected disease progression or as clinically indicated. Same 
modality used at Screening should be used throughout study.  
16. In participants with extramedullary MM, if the last radiographic assessment 
occurred ≥8 weeks prior withdrawal from study treatment, and PD has NOT been 
documented otherwise, a new assessment should be obtained at the time the 
patients withdrew from study treatment. To be performed by the same method 
throughout the study as was done at baseline (i.e. if CT/PET scan was used as 
baseline, participant needs to be followed by CT/PET scans).  Selected target 
lesion needs to be measured and followed over time (every 12 weeks). 
17. Collect one ADA at least 8 weeks post last dose. 
18. Collect one PK at least 8 weeks post last dose. 
19. MRD testing to be performed by a central lab at the time of first achieving VGPR 
or CR, repeat MRD testing every 6 after achieving VGPR or CR (provided 
VGPR/CR is maintained).   
20. Only to confirm CR/sCR or suspected PD (if not shown by other methods) at this 
visit for plasma cell assessment by IHC or aspiration. For stringent CR in 
IgD or IgE 
X13 
 
X13 
 
Calcium corrected for 
albumin (serum) 
X 
 
X 
 
Skeletal Survey 
X14,15 
 
X14,15 
 
Imaging for 
Extramedullary 
Plasmacytoma 
Assessment (by whole 
body CT or whole body 
MRI or CT/PET 
X15,16 
 
X15,16 
 
PK and ADA 
Plasma PK for GSK’916  
X 
 
 
 
Serum Immunogenicity 
(ADA) for GSK’916 and 
GSK’998. 
X 
 
X17 for 
GSK’998 
ONLY 
 
Plasma PK for GSK’998  
X 
 
X18 
 


2020N453267_00 
CONFIDENTIAL 
 
 
 
208887 Sub-study 1  
 
21 
 
Study Assessments 
End of  
Treatment 
Visit1 
 
PFS Follow-
up2 
OS 
Follow-
up3 
Notes 
All assessments will apply to both the DE and CE Phases unless stated otherwise. 
Biomarkers 
participants achieving a CR, bone marrow core biopsy is required to confirm sCR 
by IHC for light chain restriction (clonality). Only 1 marrow procedure required for 
CR and sCR assessment.  
21. Optional bone marrow aspirate sample to be collected at one of the following 
timepoints: C1D8, C1D15 or during any 3 week period for biomarker 
assessments. If possible, whenever MRD is assessed a further BM aspirate 
sample may be taken as part of the same BM draw.  Central laboratory 
assessment. 
22. Assessed in CE Phase only. 
23. Participants with ocular signs at the end of study treatment visit will have follow-
up OSDI questionnaires every 3 months (±7 days) until resolution of ocular signs 
or up to 1 year post treatment discontinuation, whichever is soonest.  
24. Must be conducted via telephone within approximately 21 days of the end of 
study visit. 
25. Optional interview to be conducted via telephone approximately 6 months after 
EoT. 
Serum (soluble BCMA) 
X 
 
 
 
Plasma-cfDNA  
X 
 
 
 
Peripheral blood for 
CMMC analysis 
X 
 
 
 
Bone Marrow (BM) Aspiration/Biospy 
MRD testing bone marrow 
aspirate 
X19,21 
 
X19 
 
BM aspirate/core biopsy 
for Disease assessment 
X20 
 
X20 
 
BM core biopsy to assess 
sCR 
X20 
 
X20 
 
BM aspirate for BCMA 
expression and immune 
cell 
characterization/profiling 
X21 
 
 
 
Health Outcomes 
PRO-CTCAE 
X22 
 
 
 
OSDI 
X22,23 
 
X22,23 
X22,23 
EORTC-QLQ-C30 and 
EORTC-IL52 
X22 
 
 
 
Qualitative interview 
X22,24 
 
X25 
X25 
Schedule survival Status 
phone call 
X3 
 
 
X3 


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ADA = Anti-drug Antibody; BP = Blood pressure; cfDNA = Circulating free DNA; CR = Complete response; CT = Computed tomography; eGFR = Estimated glomerular filtration rate; 
ECG = Electrocardiogram; ECHO = Echocardiogram; EOI = End of Infusion; EORTC-QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life 
Questionnaire 30-item Core Module; EORTC-IL52 = European Organisation for Research and Treatment of Cancer Item Library 52; FLC = Free light chain; Ig = Immunoglobulin; IHC = 
Immunohistochemistry; HR = Heart rate; MRD = Minimal residual disease; MRI = Magnetic resonance imaging; OS = Overall survival; OSDI = Ocular Surface Disease Index; PBMC 
Periferal Blod Mononuclear Cells: PD = Progressive disease; PET = Positron emission tomography; PFS = Progression free survival; PK = Pharmacokinetics; PRO-CTCAE = Patient-
Reported Outcomes Version of the Common Term Criteria for Adverse Events;; sCR = Stringent complete response; SOI = start of infusion; SPEP = Serum protein electrophoresis; T3 
= Triiodothyronine 3; T4 = Triiodothyronine 4; TSH = Thyroid Stimulating Hormone; UPEP = Urine protein electrophoresis; VGPR = Very good partial response 
 
 


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2. 
INTRODUCTION 
Please refer to the 208887 master Protocol for the overall Introduction to belantamab 
mafodotin for the study. 
Information and details specific to Sub-study 1 are in Section 2.1, Section 2.2 and Section 
2.3 below. 
2.1. 
Rationale for combination of Belantamab mafodotin with 
GSK’998 
Immunogenic cell death (ICD) is triggered by apoptotic cell death, where Damage-
Associated Molecular Pattern (DAMP) molecules either released from the dying cell into 
the extracellular microenvironment or translocated from the endoplasmic reticulum to the 
cell surface, engage the adaptive immune response and activate antigen presenting cells, 
contributing to T cell-mediated anti-tumor activity and leading to durable immunity. 
ADC-induced apoptosis by belantamab mafodotin produced DAMPs, including cell 
surface externalization of calreticulin (CRT) and secretion of high mobility group box 1 
protein (HMGB1) and ATP. ICD induced by belantamab mafodotin resulted in activation 
of dendritic cells in vitro and in vivo. In vivo, studies using a syngeneic lymphoma 
mouse model engineered to express human BCMA (EL4-hBCMA) demonstrated durable 
tumor regression, and resistance to re-challenge upon treatment with belantamab 
mafodotin. Therefore, enhanced antigen presentation through ICD, and resulting T cell-
mediated durable immunity suggests that additional therapeutic benefit can be obtained 
from combination treatment of belantamab mafodotin with immune-enhancing agents 
such as GSK’998 (aOX40). 
Pre-clinical studies in combination with belantamab mafodotin were not conducted with 
GSK’998 (aOX40) as this humanized IgG1 anti-OX40 agonistic monoclonal antibody 
does not cross-react with the mouse OX40 receptor. Therefore, a surrogate monoclonal 
antibody to murine OX40 (OX86) was used in combination with GSK’916 in non-clinical 
in vivo experiments. The experimental evidence from the combination of GSK’916 and 
OX86 in mice is described below. 
Belantamab mafodotin at 10 mg/kg combined with an IgG2a isotype control at 5 mg/kg 
resulted in no tumor-free mice at end of study. OX86 (IgG2a) monotherapy at 1 and 
5 mg/kg with an IgG1-MMAF control antibody resulted in 80% and 50% tumor-free 
mice, respectively. The change in durable tumor regressions in combination therapy 
compared to monotherapy were dependent upon the OX86 dose. In the combination 
cohorts, GSK’916 dosed at 10 mg/kg in combination with 1 mg/kg OX86 resulted in 50% 
tumor-free mice, a decrease from the 80% tumor-free mice observed with the 1 mg/kg 
OX86 alone, although this decrease was not statistically significant. Belantamab 
mafodotin in combination with 5 mg/kg OX86 resulted in 90% tumor-free mice, an 
increase from the 50% tumor-free mice observed with the 5 mg/kg OX86 alone, although 
this was also not statistically significant. In summary, OX86 in combination with 
belantamab mafodotin provided with survival benefit in mice over GSK’916 single agent 
activity; however, it did not reach statistical significance.  


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A second efficacy study was performed to verify the dose dependent effects of combining 
OX86 IgG2a (0.2, 1 or 5 mg/kg, biweekly x 3) with belantamab mafodotin (10 mg/kg, bi-
weekly x 3), n=10 female tumor-bearing mice/group. In this study, the combination of 
belantamab mafodotin with OX86 at 0.2, 1 and 5 mg/kg provided additional benefit 
compared to each single agent, by significantly increasing survival and tumor growth 
inhibition or tumor growth delay. The combination of OX86 at 0.2, 1 and 5 mg/kg with 
belantamab mafodotin resulted in 7, 4 and 5 (out of 10 mice) tumor free survivors, 
respectively, at the end of the study (Day 60). In contrast, in the monotherapy groups, 
there were no tumor free mice treated with GSK’916 or 0.2 mg/kg OX86, and only one 
tumor free mouse in each of the 1 and 5 mg/kg anti-OX86 groups. 
Changes in pharmacodynamic markers were analysed in EL4-hBCMA tumors following 
treatment with OX86 IgG2a (1 mg/kg or 5 mg/kg) and GSK’916 (10 mg/kg) dosed 
intraperitoneally biweekly x 3 in the EL4-hBCMA model. The dosing was started when 
the tumors were approximately 200 mm3 and the tissues were harvested 48 hours 
following the first or second dose. Plasma was analysed for cytokine changes, draining 
lymph nodes and tumors were analysed for changes in pharmacodynamic markers 
following the treatments. Belantamab mafodotin alone and the combination treatment 
resulted in an increase in the proportion of dendritic cells (DC) compared to the isotype 
controls. There was also a significant increase in regulatory T cells following belantamab 
mafodotin treatment. Flow cytometric analysis was carried out on the tumors obtained 
after first dose. Belantamab mafodotin alone and the combination treatment with OX86 
IgG2a resulted in an increase in the expression of the immunogenic cell death marker 
calreticulin in live tumor cells. An increase in a type I interferon gene signature was 
observed primarily in the group treated with belantamab mafodotin alone and in the 
combination with OX86 IgG2a (1 mg/kg) after one dose of treatment [GSK Internal 
Data]. 
Evidence to date does not indicate that overlapping toxicities would be expected between 
belantamab mafodotin and GSK’998 (aOX40). 
 
2.2. 
Background for GSK’998 (GSK3174998) 
GSK’998 (aOX40) is a humanized wild-type IgG1 anti-OX40 agonistic mAb. OX40 is a 
potent costimulatory receptor expressed primarily on activated CD4+ and CD8+ T-cells. 
OX40 signalling promotes effector T-cell activation and proliferation, while blocking the 
suppressive function of regulatory T cells (Tregs).  A surrogate mAb to murine OX40 
(OX86) has been shown to increase antitumor immunity and to improve tumor-free 
survival in nonclinical models.  GSK’998 (aOX40) is currently under investigation in a 
FTIH study in solid tumors, in combination with pembrolizumab in participants in solid 
tumors (Study 201212; ENGAGE-1; NCT02528357) and in combination with TLR4 
(Study 204686; NCT03447314).  Additional information on the effects of GSK’998 
(aOX40) can be found in the IB [GlaxoSmithKline Document Number 
2014N212091_05, 2018]. 


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2.2.1. 
Clinical pharmacology data with GSK’998 
As of a clinical data cut-off date of 13 Aug 2017, a total of 82 participants with advanced 
solid tumors have been treated in the ongoing FTIH study 201212. Forty-five received 
monotherapy GSK’998 (aOX40) at doses between 0.003-10 mg/kg intravenously (IV) 
once every 3 weeks  
In Study 201212, the PK of GSK’998 (aOX40) administered as single-agent 
monotherapy was evaluated after IV administration at doses of 0.003 mg/kg to 10 mg/kg 
every 3 weeks in patients with solid tumors.   
The GSK’998 (aOX40) concentration-time profiles [GlaxoSmithKline Document 
Number 2014N212091_05, 2018] initially exhibited a bi-exponential decline typical for 
IV-administered mAbs. At lower GSK’998 (aOX40) concentrations, faster elimination 
and shorter half-lives were observed, indicating target-mediated disposition.  
Consequently, AUC and trough concentrations were increasing more than proportionally 
with dose.  GSK’998 (aOX40) Cmax values normalized by dose for Cycle 1 indicated 
dose-proportionality for Cmax and Cmax values were typical for mAbs. 
At a data cut-off date of 22 Jun 2017, 49% of participants with available post-treatment 
data tested positive for anti- GSK’998 (aOX40) anti-drug antibodies (ADA) across dose 
levels 0.003–10 mg/kg GSK’998 (aOX40) in Part 1A (monotherapy) and 0.003–
0.1 mg/kg in Part 2A (combination therapy).  Positive ADA titers were detectable as 
early as 3 weeks after the first dose of GSK’998 (aOX40).  Of the 30 participants with 
positive ADA titres, two participants experienced infusion related reactions beginning 
with administration of the third dose of GSK’998 (aOX40); no other infusion reactions 
have been reported in the study to date. 
Receptor occupancy (RO) was assessed for peripheral blood CD3+ T cells in study 
201212.  Preliminary data indicated that a high degree (≥80%) of receptor occupancy is 
achieved initially (≤1 day after dosing) even for the lowest dose of 0.003 mg/kg 
GSK’998 (aOX40). For doses of 0.1 mg/kg or smaller, receptor occupancy subsequently 
declines towards the end of the dosing cycle.  At doses of GSK’998 (aOX40) 0.3 mg/kg 
or greater, continuously high receptor occupancy levels are observed over the whole 21-
day dosing cycle.  
2.2.2. 
Safety Data for GSK’998 (GSK3174998) monotherapy 
No dose-limiting toxicities, or treatment-related Grade 4, or Grade 5 toxicities were 
reported for doses from 0.003mg/kg to 10mg/kg. One event of Grade 3 asthenia and 
lymphocytopenia were reported independently in a single patient and attributed to study 
treatment.  A single event led to treatment discontinuation, Grade 5 stroke manifested as 
aphasia, attributed to disease progression.  
The most common AEs reported with GSK’998 (aOX40) monotherapy included fatigue 
(11, 24%), back pain (9, 20%), diarrhea (9, 20%), nausea (9, 20%), asthenia (8, 18%), 
vomiting (8, 18%), anemia, (7, 16%), headache (6, 13%), dyspnoea (5, 11%), myalgia (5, 
11%), pain in extremity (5, 11%), and pyrexia (5, 11%).  The most common treatment 


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related AEs included diarrhea (5, 11%) and fatigue (5, 11%) [GlaxoSmithKline 
Document Number 2014N212091_05, 2018]. 
2.2.3. 
Clinical Activity of GSK’998 Monotherapy 
At the time of the clinical data cut-off (13 Aug 2017), one confirmed PR was reported in 
a participant with soft tissue sarcoma (STS), who subsequently discontinued treatment for 
PD at Week 30.  A second participant with NSCLC was reported to have SD for 
24 weeks, and discontinued treatment with PD after 39 weeks.  Both of these participants 
received a GSK’998 dose of 0.3 mg/kg (equivalent to 24 mg) administered once every 
3 weeks.  An additional 5 participants were reported to have SD at Week 12, but 
subsequently discontinued treatment for PD prior the next imaging assessment. 
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and 
reasonably expected adverse events of GSK’998 may be found in the Investigator’s 
Brochure (IB) [GlaxoSmithKline Document Number 2014N212091_05, 2018]. . 
 


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2.3.1. 
Risk Assessment 
Table 6 outlines the risk assessment and mitigation strategy for GSK’998 (aOX40).  Belantamab mafodotin risk assessment and 
mitigation strategies are in the 208887 MP (see Section 2.3.1).  
Table 6 
Risks related to GSK’998 (aOX40) 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Risk related to GSK’998 (aOX40) 
Infusion-related reactions (IRRs) and 
hypersensitivity 
Risk for IRRs and hypersensitivity is inherent to 
many mAbs [Brennan, 2010]. 
 
FTIH study of GSK’998 (aOX40) observed a 6% rate 
of IRR. Most IRRs observed in the clinic to date 
have been Grade 1 to 2, manageable with medical 
treatment.  
Participants with history of severe hypersensitivity to 
another mAb ineligible for this study  
Refer to 208887 MP Section 11 for further details on 
management of infusion reactions.  
Immune-related AEs 
Monoclonal antibodies which affect the acquired 
immune system and promote the killing of tumor 
cells (e.g., ipiliumumab, pembrolizumab and 
nivolumab) have been associated with inflammatory 
AEs such as diarrhea/colitis, pneumonitis, nephritis, 
hypophysitis, adrenalitis, thyroiditis, severe skin 
reactions, uveiitis, myocarditis and hepatotoxicity. 
These are well established after treatment with 
checkpoint modulators, and are consistent with the 
immune-stimulatory mechanism of action of these 
agents. Currently, data are insufficient to fully 
appreciate the characteristics of GSK’998 (aOX40) 
in this regard; however, surveillance for events of 
this nature is warranted. 
Participants with the following medical history are 
ineligible for this study 
o Toxicity (Grade ≥3) related to prior 
immunotherapy leading to study treatment 
discontinuation  
o Active autoimmune disease  
o Severe hypersensitivity to another mAb 
Established management algorithms for irAEs: Refer 
to 208887 MP Section 11 for further details on the 
identification, evaluation, and management of 
toxicities including cumulative effects, with a 
potential immune etiology. 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Belantamab mafodotin preclinical data indicate a 
potential for systemic inflammation and may 
potentiate any immune or inflammatory related AEs 
in combination with OX40. 
Severe cytokine release syndrome (sCRS) 
OX40 is a co-stimulatory receptor that can stimulate 
proliferation and activation of T-cells. 
GSK’998 (aOX40) is an OX40 agonist that can co-
stimulate T-cell activation in the context of TCR 
signal and CD28 co-signal and could potentially 
cause severe cytokine release syndrome. No CRS 
has been observed in the clinic in the OX40 FTIH 
study as of the data cutoff. 
Management guidelines have been included in 
208887 MP Section 11. 
 
 


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2.3.2. 
Benefit Assessment 
Study participants may benefit from medical tests and screening performed during the 
study.  Any potential benefit of the addition of GSK’998 (aOX40) to belantamab 
mafodotin is unknown.  Data obtained in this study may help identify individuals more 
likely to benefit or have side-effects from GSK’998 (aOX40) plus belantamab mafodotin. 
OX40 agonists have been shown to increase antitumor immunity and improve tumor-free 
survival in non-clinical models and OX40 agonist monoclonal antibodies (mAbs) are 
currently being evaluated in Phase I clinical trials. 
2.3.3. 
Overall Benefit: Risk Conclusion 
This is the first study testing the combination of GSK’998 (aOX40) plus belantamab 
mafodotin in participants with relapsed/refractory multiple myeloma that have been 
treated with standard therapies.   
Considering the measures taken to minimize risks to subjects participating in the Phase I 
clinical trial, the potential risks identified in association with GSK’998 (aOX40) as a 
monotherapy or combination therapy are justified by the anticipated benefits that may be 
afforded to subjects with relapsed/refractory solid tumors. 
3. 
OBJECTIVES AND ENDPOINTS 
The primary, secondary and, exploratory objectives, along with the corresponding 
endpoints for both Dose Exploration and for Cohort Expansion are identical to those 
listed in the 208887 MP Section 3. 
4. 
STUDY DESIGN 
Please refer to the 208887 Master Protocol for the overall Study Design for the study. 
Information and details specific to Sub-study 1 are in Section 4.1 and Section 4.3 below. 
4.1. 
Overall Design  
Overall design is in relation to the dose exploration of combination treatment Belantamab 
mafodotin co-administered with GSK’998 (aOX40) being described in this Sub-study. 
A total of 3 dose levels can be potentially evaluated (Table 7).  Therefore, in the aOX40 
sub-study, there could potentially be a maximum of 3 dosing cohorts running 
simultaneously in the dose exploration (DE) phase.  At Dose Level 1, the starting dose of 
belantamab mafodotin will be 1.9 mg/kg and the starting dose of GSK’998 (aOX40) will 
be 8 mg. From the emergent safety data at Dose Levels 1 and 2, the 8 mg dose of 
GSK’998 (aOX40) can be escalated to 24 mg in combination with 2.5 mg/kg belantamab 
mafodotin.  At Dose Level 3, the maximum dose of belantamab mafodotin will be 
2.5 mg/kg and the maximum dose of GSK’998 (aOX40) will be 24 mg.  Sponsor may 
decide not to evaluate all dose levels based on data external to this study.  Please see 
208887 MP Section 4.1.1 for details of decision making during the DE phase. 


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Table 7 
Dose Exploration Schema Belantamab mafodotin in combination 
with GSK’998 (aOX40)  
Dose level 
Belantamab mafodotin 
dose 
GSK’998 (aOX40) dose 
1 (starting dose level) 
1.9 mg/kg 
8 mg 
2 
2.5 mg/kg 
8 mg 
3 
2.5 mg/kg 
24 mg 
 
4.2. 
Scientific Rationale for Study Design 
4.3. 
Justification for Dose 
GSK’998 (aOX40) will initially be administered at a flat dose of 8 mg IV Q3W on Day 1 
of each 21-day cycle after the infusion with belantamab mafodotin. Please refer to 
208887 MP Section 4.3 for starting dose of belantamab mafodotin. 
Previous clinical experience for GSK’998 (aOX40) in Study 201212 [NCT02528357] 
was based on weight-proportional dosing. The 8 mg dose to be tested in this study is 
considered equivalent to the 0.1 mg/kg dose in the ongoing FTIH trial [NCT02528357], 
assuming a median participant weight of 80 kg.  
The 8-mg dose of GSK’998 (aOX40) is considered an appropriate dose for combination 
therapy with belantamab mafodotin based on the following: According to currently 
available data, the starting dose of 8 mg was well tolerated and did not result in excessive 
toxicity in advanced solid tumor patients.  Doses up to 10 mg/kg (800 mg equivalent) 
GSK’998 (aOX40) monotherapy tested in the ongoing FTIH trial [NCT02528357] did 
not result in DLTs and an MTD was not established. To date, there is no apparent dose-
toxicity response with GSK’998 monotherapy. The starting dose of 8 mg results in 
exposure approximately 100-fold lower than the 10 mg/kg dose. 
In the ongoing FTIH trial in participants with advanced solid tumors [NCT02528357] the 
GSK’998 dose level of 0.1 mg/kg (equivalent to 8 mg) represents one dose level below 
the dose (0.3 mg/kg, equivalent to 24 mg) that demonstrated linear PK, saturation of 
peripheral OXO40 RO across the dosing interval, and clinical activity. No clinical 
activity was observed for GSK’998 monotherapy 0.1 mg/kg in participants with solid 
tumors; however, evidence of some pharmacological target engagement was observed, 
with ~30% RO by Week 3 post-dose compared ~85% RO for the 0.3 mg/kg dose level. 
GSK’998 0.1 mg/kg trough plasma concentrations dropped below the level of 
quantification by Week 3, whereas 0.3 mg/kg trough concentrations remained 
measurable. Thus, an 8 mg (0.1 mg/kg equivalent) dose of GSK’998 is considered to 
balance appropriate tolerability with the potential for exposing participants to 
subtherapeutic doses.   


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Based on the large capacity, non-specific clearance, and recycling mechanisms for mAbs, 
no DDI related to non-specific IgG turnover is expected between belantamab mafodotin 
and GSK’998 (aOX40) for the dose ranges considered.  
Because the ligands of belantamab mafodotin and GSK3174998 are expressed on 
different target cell populations, no DDI related to target mediated disposition is expected 
between belantamab mafodotin and GSK’998 (aOX40). 
The safety profiles of both antibodies currently do not suggest overlapping toxicity. 
Therefore, a starting dose of 8 mg (0.1 mg/kg equivalent) IV Q3W is anticipated to be 
well tolerated without excessive, treatment-related toxicity in this RRMM participant 
population. 
4.4. 
Participant Completion and End of Study Definition 
There is no change in this section from the 208887 MP. 
4.4.1. 
Participant Completion Definitions: 
A participant is considered to have completed the study if they received at least 1 cycle of 
combination study treatment, and the participant is followed until death (even after 
starting a new anti-cancer treatment) or until the end of the study. 
4.4.2. 
Study Completion: 
Sub-study completion: For the DE and CE phases, a sub-study is considered to have 
completed if all participants have been followed up for 36 months, withdrawn consent, 
are lost to follow up, or died.  A sub-study may close after or during DE for safety or 
tolerability reasons or if an insufficient number of responders have been observed.  
The end of study (EOS) is the last visit of the last participant in the last sub-study. This 
will occur when the last participant has been followed up for 36 months, died, withdrawn 
consent or is lost to follow-up. Any patient who has not reached PD at this time will be 
treated in a separate study roll over study or at the investigators’ discretion.  
5. 
STUDY POPULATION 
Please refer to the 208887 MP for the overall planned Study Population details for the 
study. 
Information and details specific to Sub-study 1 are in Section 5.2 below. 
Participants are eligible to be included in the study only if all of the criteria in Section 
5.2, and in 208887 MP Section 5.1 and Section 5.2 apply.  Prospective approval of 
protocol deviations to recruitment and enrollment criteria, also known as protocol 
waivers or exemptions, is not permitted. 


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5.1. 
Inclusion Criteria for Participants 
There are no additional inclusion criteria for Sub-study 1.   
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
The exclusion criteria #26 and #27 below are in addition to the exclusion criteria already 
defined in 208887 MP Section 5.2.   
26. Autoimmune disease (current or history) or syndrome that required systemic 
treatment within the past 2 years.  Replacement therapies which include, 
physiological doses of corticosteroids for treatment of endocrinopathies (for 
example, adrenal insufficiency) or treatment of hypothyroidism is allowed on study. 
27. In addition, exclusion for a recent (within the past 6 months) history of symptomatic 
pericarditis. 
5.3. 
Lifestyle Considerations 
5.4. 
Screen Failures 
 
6. 
STUDY INTERVENTION 
Please refer to the 208887 MP for the overall Study Intervention for the study. 
Information and details specific to Sub-study 1 are in Section 6.1, Section 6.2 and Section 
6.6 below. 
Study intervention is defined as belantamab mafodotin administered with GSK’998 
treatment and administered to a study participant according to the study protocol. 


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6.1. 
Study Intervention(s) Administered 
Specifications for belantamab mafodotin and GSK’998 IP in this study are given (Table 
8).   
Table 8 
Belantamab mafodotin and GSK’998 
Intervention Name 
Belantamab mafodotin 
GSK’998 (OX40) 
Type  
Drug  
Drug 
Dose Formulation 
Powder for solution for infusion 
Powder for solution for infusion 
Unit Dose Strength(s) 
100 mg/vial  
40 mg/vial  
Route of Administration 
Delivered as IV solution, infused over 30-
60 minutes 
Delivered as IV solution over 30 minutes 
IMP  
GSK2857916 (belantamab mafodotin) 
GSK3174998 
Sourcing 
GSK 
GSK 
Packaging and Labelling 
 
Study Intervention will be provided in 
vials. Each vial will be labeled as required 
per country requirement. 
Study Intervention will be provided in vials. 
Each vial will be labeled as required per 
country requirement. 
 
6.2. 
Administration of Belantamab mafodotin and GSK’998 
• 
Belantamab mafodotin will be administered before administration of GSK’998 
(aOX40). 
• 
GSK’998 (aOX40) will be administered via IV infusion on D1 of every 21 day cycle 
• 
Belantamab mafodotin will be administered to subjects intravenously as mg/kg 
calculated dose at the study site.  The dose to be administered is based on actual 
body weight calculation and may be reduced for toxicity according to protocol 
guidelines.  
• 
Administration will be documented in the source documents (208887 MP Section 
12.1.8) and reported in the eCRF.  The time of start and end of infusion will be 
documented in eCRF. 
• 
Belantamab mafodotin (Section 6.1) will be administered on Day 1 of each cycle at 
the assigned dose as an IV infusion.  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.  In case of infusion related 
reactions related to belantamab mafodotin the rules outlined in 208887 MP Section 
7.1.6 and Section 11 should be followed.  
• 
After the infusion of belantamab mafodotin has been completed subjects will be 
required to enter at least 1-hour rest period before starting GSK’998 (aOX40) 
infusion where appropriate.  
• 
The intended cycle time of GSK’916 BCMA as a monotherapy is 21 days (+3-day 
window) and cannot occur more frequently than this.  
 


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Table 9 
Route of Administration and Dose Timing for Belantamab mafodotin 
and GSK’998 in the DE phase 
 
Belantamab mafodotin 
GSK’998 (aOX40) 
Route of 
administration 
IV infusion (see Section 6.1 for details) 
IV infusion (see Section 4.1 for details) 
Timing 
Administer first, on day 1 of 21 day 
cycles 
Start 1 h after belantamab mafodotin EOI 
on day 1 of 21 day cycles. For guidance 
about dosing if an infusion related reaction 
(IRR) occurs please see 208887 MP 
Section 11. 
Participants enrolled in the DE phase and the CE phase will be treated until disease 
progression, intolerable toxicity, informed consent withdrawal, the end of the sub-study, 
study or death.   
6.3. 
Preparation/Handling/Storage/Accountability 
6.4. 
Measures to Minimize Bias: Randomization and Blinding 
6.5. 
Concomitant Therapy 
6.6. 
Dose Modification  
Dose modification is for Belantamab Mafodotin when in Combination with GSK’998.  
For information related to overall dose modification refer to the 208887 Master Protocol.  
Also see 208887 MP Section 11 for guidelines on dose modification and management of 
events for belantamab mafodotin and other partner combination treatments. 
6.6.1. 
Permitted Dose Reductions for Belantamab Mafodotin when in 
combination with GSK’998 
• 
For further details regarding dose modifications see Section 6.6 for belantamab 
mafodotin and 208887 MP Section 11. 
 
Table 10 
Permitted dose reductions for Belantamab mafodotin when in 
combination with GSK’998 (aOX40) 
Belantamab mafodotin Dose 
Level 
1st Dose Reduction 
2.5 mg/kg 
1.9 mg/kg 
1.9 mg/kg 
- 
 
• 
The dose of GSK’998 (aOX40) will not be modified. Please refer to Section 2.3. 
• 
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 one dose reduction of belantamab mafodotin (to 1.9 mg/kg) is permitted from 
any 2.5 mg/kg belantamab mafodotin dose level in Table 10. 


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• 
No dose reduction of belantamab mafodotin is permitted from the starting dose level 
of 1.9 mg/kg as lower doses are likely to be inefficacious based on findings from 
Part 1 of the FTIH trial (GSK Study BMA117159). 
• 
In case of full resolution of symptoms which lead to dose reduction, further 
treatment with belantamab mafodotin at the initially-assigned dose may be 
considered by the investigator.  
• 
Resuming treatment with belantamab mafodotin may be possible after the toxicity 
has resolved to Grade 1 or less.   
• 
If GSK’998 (aOX40) is permanently withdrawn the participant can remain on 
belantamab mafodotin, if belantamab mafodotin is permanently withdrawn the 
participant will be withdrawn from all study treatment. 
6.6.2. 
Permitted Dose Modifications of GSK’998 when in combination 
with Belantamab mafodotin 
There are no dose modifications allowed for GSK’998 (aOX40).  Fixed (flat) dosing of 
GSK’998 (aOX40) will be used during the study for all participants receiving GSK’998 
(aOX40), regardless of participant weight. 
Dosing of GSK’998 (aOX40) may be delayed if needed, but this will not affect the 
dosing schedule for belantamab mafodotin.  GSK’998 may only be administered with 
GSK’916 with the possibility of GSK’998 administration 1 day later than GSK’916 in the 
case of an IRR on the date of GSK’916 infusion.  The maximum treatment delay to 
GSK’916 treatment is 16 weeks and therefore the maximum treatment delay to GSK’998 
is 16 weeks +1 day, unless agreed in writing by the Medical Director.  Please refer to 
208887 MP Section 11 for details on management of adverse events requiring delay or 
discontinuation of GSK’998 (aOX40) dosing. 
If belantamab mafodotin is delayed for any reason, then GSK’998 (aOX40) will also 
be delayed.  
If participants develop toxicity which would preclude additional dosing with GSK’998 
(aOX40), they can continue with belantamab mafodotin only.  For drug-related toxicities 
not listed in these tables, the general rule of withholding the dose for Grade ≥3 toxicity 
should be followed.  Resuming treatment will be possible with or without dose reduction 
after the toxicity has resolved to Grade ≤1 and with agreement between the principal 
investigator (PI) and GSK Medical Director.  
Investigators must contact the GSK Medical Director for all Grade ≥3 clinically 
significant non-hematological drug-related toxicities where interruption or permanent 
discontinuation of study treatment may be warranted according to the guidelines provided 
in 208887 MP Section 11. Otherwise, investigators are encouraged to contact the GSK 
Medical Director as needed to discuss any case that warrants separate discussion outside 
of the scope of current guidelines. 
 


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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT WITHDRAWAL FROM THE STUDY 
Please refer to the 208887 MP for the information contained in the Level 2 headings 
below. 
7.1. 
Discontinuation of Study Intervention 
7.2. 
Participant Withdrawal from the Study 
7.3. 
Lost to Follow Up 
 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
Please refer to the 208887 MP for the overall Study Assessments and Procedures for the 
study. 
Information and details specific to Sub-study 1 are in Section 8.3.7, Section 8.3.10 and 
Section 8.4 below. 
8.1. 
Efficacy Assessments 
8.2. 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA tables (Section 
1.3).   
8.3. 
Adverse Events and Serious Adverse Events  
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information 
8.3.2. 
Method of Recording AE and SAE Information 
8.3.3. 
Method of Detecting AEs and SAEs 
8.3.4. 
Follow-up of AEs and SAEs 
8.3.5. 
Reporting of Potentially Life-Threatening AEs to the GSK Medical Director 
8.3.6. 
Regulatory Reporting Requirements for SAEs 
8.3.7. 
Management of Pregnancy 
Details of all pregnancies in female participants will be collected after the start of study 
treatment and for 8 months following last dose of belantamab mafodotin. 
Details of all pregnancies for female partners of male participants will be collected after 
the start of study treatment and 5 months following last dose of belantamab mafodotin. 


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8.3.8. 
Cardiovascular and Death Events 
8.3.9. 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
SAEs 
8.3.10. 
Adverse Events of Special Interest 
Information on belantamab mafodotin AESI are contained in the 208887 MP Section 
8.3.10. 
Adverse Events of Special Interest for GSK’998 
The list of terms and reporting requirements for GSK AESI are provided below.  These 
are selected non-serious AEs and SAEs that must be reported to GSK regardless of 
relationship to study treatment.  For participants who experience signs or symptoms that 
may be consistent with an AESI, sites are strongly encouraged to immediately notify the 
GSK Medical Director of the event via email and/or phone.  Documentation of potential 
AESIs should occur after discussion between the investigator and the sponsor/Medical 
Director. Even events without clear confirmation of their immunologic etiology may 
qualify as AESIs. Many of these events may also qualify as SAEs.  Details are available 
in the SRM. Any event that meets the criteria described below must be reported 
regardless of investigator-determined relationship to study treatment or if considered 
immune-related (unless otherwise specified).  Investigators/study coordinators/designated 
site personnel are required to record these experiences in the eCRF (as described in the 
eCRF completion guidance document) and to provide supplemental information (such as 
medical history, concomitant medications, investigations, etc.) about the event.  Please 
note this table lists known AESI, additional events may be identified during the course of 
the study. 
Table 11 
Immune-related AEs for GSK’998 Treatment 
Pneumonitis (reported as AESI if Grade ≥2) 
Acute interstitial pneumonitis 
Interstitial lung disease 
Pneumonitis 
Colitis (reported as AESI if Grade ≥2 or any grade resulting in dose modification or use of 
systemic steroids to treat the AE) 
Intestinal Obstruction 
Colitis 
Colitis microscopic 
Enterocolitis 
Enterocolitis hemorrhagic 
Gastrointestinal perforation 
Necrotizing colitis 
Diarrhea 
 
Endocrine (reported as AESI if Grade ≥3 or Grade ≥2 and resulting in dose modification or use 
of systemic steroids to treat the AE) 
Adrenal Insufficiency 
Hyperthyroidism 
Hypophysitis 
Hypopituitarism 
Hypothyroidism 
Thyroid disorder 
Thyroiditis 
Hyperglycemia, if Grade ≥3 and associated with ketosis or 
metabolic acidosis (DKA) 


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Endocrine (reported as AESI) 
Type 1 diabetes mellitus (if new 
onset) 
 
 
Hematologic (reported as AESI if Grade ≥3 or any grade resulting in dose modification or use of 
systemic steroids to treat the AE) 
Autoimmune hemolytic anemia  
Aplastic anemia  
Thrombotic 
Thrombocytopenic Purpura 
(TTP) 
Idiopathic (or immune) 
Thrombocytopenia Purpura (ITP) 
Disseminated Intravascular 
Coagulation (DIC) 
Hemolytic Uremic Syndrome 
(HUS) 
Any Grade 4 anemia regardless of underlying mechanism 
Hepatic (reported as AESI if Grade ≥2, or any grade resulting in dose modification or use of 
systemic steroids to treat the AE) 
Hepatitis  
Autoimmune hepatitis  
Transaminase elevations 
(ALT and/or AST) 
Infusion Reactions (reported as AESI for any grade) 
Allergic reaction 
Anaphylaxis 
Cytokine release syndrome 
Serum sickness 
Infusion reactions 
Infusion-like reactions 
Neurologic (reported as AESI for any grade) 
Autoimmune neuropathy 
Guillain-Barré syndrome 
Demyelinating 
polyneuropathy 
Myasthenic syndrome 
 
 
Ocular (report as AESI if Grade ≥2 or any grade resulting in dose modification or use of 
systemic steroids to treat the AE) 
Uveitis 
Iritis 
 
Renal (reported as AESI if Grade ≥2)  
Nephritis 
Nephritis autoimmune 
Renal Failure 
Renal failure acute 
Creatinine elevations (report as AESI if Grade ≥3 or any 
grade resulting in dose modification or use of systemic 
steroids to treat the AE) 
Skin (reported as AESI for any grade) 
Dermatitis exfoliative 
Erythema multiforme 
Stevens-Johnson syndrome 
Toxic epidermal necrolysis 
 
 
Skin (reported as AESI if Grade ≥3) 
Pruritus 
Rash 
Rash generalized 
Rash maculo-papular 
 
 
Any rash considered clinically significant in the physician’s judgment  
Other (reported as AESI for any grade) 
Myocarditis 
Pancreatitis 
Pericarditis 
Any other Grade 3 event which is considered immune-related by the physician 
 
8.4. 
Treatment of Overdose  
Guidelines for management of belantamab mafodotin overdose are contained in the 
208887 MP Section 8.4. 


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There is no specific antidote for overdose with GSK3174998 (aOX40).  In the event of a 
suspected overdose, it is recommended that the appropriate supportive clinical care 
should be instituted, as dictated by the subject’s clinical status. 
8.5. 
Pharmacokinetics 
8.6. 
Genetics 
8.7. 
Immunogenicity Assessments 
8.8. 
Biomarkers 
8.9. 
Health-Related Quality of Life 
 
9. 
STATISTICAL CONSIDERATIONS 
Please refer to the 208887 MP for the overall Statistical Considerations for the study. 
9.1. 
Statistical Hypotheses 
9.2. 
Sample Size Determination 
9.3. 
Populations for Analyses 
9.4. 
Statistical Analyses 
9.5. 
Interim Analysis 
9.6. 
Sample Size Sensitivity 
 


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10. 
REFERENCES 
Brennan FR, Morton LD, Spindeldreher S, Kiessling A, Allenspach R, Hey A, et al. 
Safety and immunotoxicity assessment of immunomodulatory monoclonal antibodies. 
mAbs. 2010; 2:233-255. 
GlaxoSmithKline Document Number 2014N212091_05 version 4.  GSK3174998 
Investigator's Brochure. Report Date 11 December 2018. 
GSK Internal Data Report 2018N384579, IND119333 Sequence No. 0114. 
 


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11. 
GUIDELINES FOR DOSE MODIFICATION AND OTHER 
PARTNER COMBINATION TREATMENTS FOR ALL 
SUBSTUDIES 
Please refer to the 208887 MP for the overall Guidelines for Dose Modification for the 
study. 
 
12. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
Please refer to the 208887 MP for the overall Supporting documentation and operational 
considerations for the study. 
Any information and details specific to Sub-study 1 are in Section 12.12 and Section 
12.13 below. 
12.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
12.2. 
Appendix 2: Clinical Laboratory Tests 
12.3. 
Appendix 3: AEs: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting 
12.4. 
Appendix 4: ECOG Performance Status 
12.5. 
Appendix 5: NYHA Functional Classification System 
12.6. 
Appendix 6: Modified Diet in Renal Disease 
12.7. 
Appendix 7: Contraceptive Guidance and Collection of Pregnancy Information 
12.8. 
Appendix 8: Genetics 
12.9. 
Appendix 9: Liver Safety: Required Actions and Follow-up Assessments and 
Study Treatment Rechallenge Guidelines 
12.10. 
Appendix 10: Eye Care Specialist- Qualifications and Requirements 
12.11. 
Appendix 11: Home Healthcare and Telemedicine Approaches 


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12.12. 
Appendix 12: Abbreviations and Trademarks 
 
ADA 
Anti-drug antibody 
ADC 
Antibody drug conjugate 
ADCC 
Antibody dependent cellular cytotoxicity 
AE 
Adverse event 
AESI 
Adverse events of Special Interest 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration-time curve 
BCMA 
B cell maturation antigen 
BCVA 
Best corrected visual acuity 
CBC 
Complete blood count 
CBR 
Clinical benefit rate 
CE 
Cohort Expansion phase 
cfDNA 
Cell-free deoxyribonucleic acid 
CI 
Confidence interval 
CK 
Creatine kinase 
CL 
Clearance 
Cmax 
Maximum plasma drug concentration 
CMMC 
Circulating multiple myeloma cells 
CPMS 
Clinical Pharmacology Modeling and Simulation 
CR 
Complete response 
CRP 
C-reactive protein 
CRT 
Calreticulin  
CT 
Computer tomography 
CTCAE 
Common Toxicity Criteria for Adverse Events 
Cys-mcMMAF 
cys Monomethyl auristatin F  
DAMP 
Damage-Associated Molecular Pattern 
DC 
Dendritic cells 
DE 
Dose Exploration phase 
DIC 
Disseminated intravascular coagulation 
DoR 
Duration of response 
DLBCL 
Diffuse large B-cell lymphoma 
DLT 
Dose limiting toxicity 
DNA 
Deoxyribonucleic acid 
EC 
Ethics committee 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
eGFR 
Estimated Glomerular Filtration (eGFR) 
EOI 
End of infusion 


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EORTC QLQ 
European Organisation for Research and Treatment of Cancer 
Quality of Life Questionnaires 
FISH 
Fluorescence in situ hybridization; 
FLC 
Free light chain 
FSH 
Follicle stimulating hormone 
FTIH 
First time in human 
GFR 
Glomerular filtration rate 
GSK 
GlaxoSmithKline 
GSK2857914 
GlaxoSmithKline anti-BCMA antibody (CA8 J6M0 Potelligent) 
GSK2857916 
GlaxoSmithKline anti-BCMA antibody drug conjugate (CA8 J6M0 
Potelligent MMAF) 
HBs-Ag 
Hepatitis B surface antigen 
HBc 
Hepatitis B core 
HbcAb 
Hepatitis B core antibody 
HBV 
Hepatitis B 
HCV 
Hepatitis C 
HMGB1 
High mobility group box 1 
ICD 
Immunogenic cell death 
ICF 
Informed consent form 
ICH 
International Council on Harmonization 
IEC 
Institutional ethics committee 
Ig 
Immunoglobulin 
IHC 
Immunohistochemistry 
IMWG 
International Myeloma Working Group 
IP 
Investigational Product 
IRB 
Institutional review board 
IRR 
Infusion-related reaction 
ITT 
Intent-to-treat 
IV 
Intravenous 
LBCL 
Large B-cell lymphoma 
LFT 
Liver function test 
LLN 
Lower limit of normal 
LVEF 
Left ventricular ejection fraction 
mAb 
Monoclonal antibody 
MDRD 
Modified diet in renal disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
MM 
Multiple Myeloma 
MMAF 
Monomethyl auristatin F 
MoA 
Mechanism of action 
MP 
Master Protocol 
MR 
Minimal response 
MRD 
Minimal residual disease 
MRI 
Magnetic resonance Imaging 
MTD 
Maximum Tolerated Dose 
NCI-CTCAE 
National Cancer Institute – Common Toxicity Criteria for Adverse 
Events 


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NT-proBNP 
N-terminal B-type natriuretic peptide 
NK 
Natural killer 
NYHA 
New York Heart Association 
ORR 
Overall response rate 
OS 
Overall survival 
OSDI 
Ocular Surface Disease Index 
PBMC 
Peripheral blood mononuclear cells 
PD 
Progressive disease 
PET 
Probability of early termination 
PFS 
Progression-free survival 
PI 
Proteasome inhibitor 
PK 
Pharmacokinetic(s) 
PR 
Partial response 
PRO 
Patient reported outcome 
Q3W 
Every 3 week 
QoL 
Quality of life 
RAP 
Reporting and analysis plan 
RNA 
Ribonucleic acid 
RO 
Receptor occupancy 
RP2D 
Recommended Phase 2 dose 
RRMM 
Relapsed/refractory multiple myeloma 
SAE 
Serious adverse event 
sBCMA 
Soluble B-cell maturation antigen 
sCR 
Stringent complete response 
SD 
Stable disease 
SoA 
Schedule of Activities 
SoC 
Standard of care 
SOI 
Start of infusion 
SPEP 
Serum protein electrophoresis 
SRM 
Study research manual 
t½  
Half-life 
TTP 
Time to progression 
TTR 
Time to response 
ULN 
Upper limit of normal 
UPEP 
Urine protein electrophoresis 
VGPR 
Very good partial response 
WOCBP 
Women of childbearing potential 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
None 
 
None 
 
 
 
 


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12.13. 
Appendix 13: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current Amendment 04 is 
located directly before the Table of Contents (ToC). 
Protocol Amendment 3 (08-JUL-2020) 
Germany Participation 
Sub-study 1 is not applicable for Germany at this time and centers in Germany will not 
participate in Sub-study 1. 
Protocol Amendment 3 Summary of Changes Specific to Sub-study 1 
The protocol has been amended to introduce a new sub-study into Section 14 of the 
protocol.  In addition, changes were made in line with comments from regulators, 
program level changes and safety updates, which include the following: 
• Removal of post-baseline ECG assessments 
• Modifications to the Dose Escalation Plan (DEP) 
• Revised guidance added for belantamab mafodotin overdose 
• Revisions to statistical projections and analyses due to addition of Sub-study 4 
• Replaced asset number or abbreviations with generic name belantamab 
mafodotin 
• Included reference Lonial, 2020 to support 2.5 mg/kg starting dose and removal 
of references to 3.4 mg/kg dose 
• Guidance on dose modifications modified to include/change management of 
IRRs, urine dipstick results, thrombocytopenia, neutropenia without fever, 
pneumonitis 
• Modified text on Risk Assessment for thrombocytopenia, potential 
cardiotoxicity, immunosuppression 
• Minor editorial and document formatting revisions 
Section # and Name 
Description of Change 
Brief Rationale 
Revised Study Design 
Section 11.6 
Change from 4 to 3 dose levels 
See Lonial, 2020 reference for 
monotherapy recommended dose  
Section 11.12.1 
Added exclusion for recent symptomatic 
pericarditis 
To better define appropriate study 
population 
Safety Changes 
Section 11.8.2 
Change dose reduction table 
As above, see Lonial, 2020 
reference for monotherapy 
recommended dose. 
Section 11.8.4 
Added section on aOX40 overdose 
To provide available guidance on 
overdose 
Changes in Assessments and SoAs 
Section 11.2 
Specified follow-up ADA assessment for aOX40 
Clarified immunogenicity 
assessments 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 11.2 
Revised assessments and descriptions, 
including: 
Urinalysis assessment and description 
Removal of post-baseline ECG assessments, 
NT-proBNP, troponin 
Description of MRI, CT, PET/CT scans for 
disease assessment in Germany 
Provide clarifications and more 
specific guidance, as with Master 
Protocol 
Section 11.2 
Added optional follow-up Qualitative phone 
interview 
Clarified timepoint assessment for 
qualitative phone interview 
Protocol Clarification and Alignment 
Section 11.2 
Replace ophthalmologist and optometrist with 
eye-care specialist term and define same  
Simplify and define provider 
terminology 
Section 11.2,  
Revisions to QoL assessments to include IL52 
(symptom assessment) portion of EORTC QLQ-
My20 and revise timepoints  
Clarify assessments and 
timingUpdated QoLassessment 
reflects disease symptom portion of  
Throughout 
Asset numbers/abbreviations replaced with 
generic names except for laboratory sampling 
For consistency throughout 
document 
Editing, format, style changes 
Throughout 
Correction of typos and technical document 
aspects 
Minor changes with no impact on 
content 
 
Protocol Amendment 2 (16-DEC-2019) 
Protocol Amendment 2 Summary of Changes Specific to Sub-study 1 
Section # and Name 
Description of Change 
Brief Rationale 
Revised Study Design 
Section 11.2, 11.13.1 
Updated pregnancy wording: follow up timing 
and management of pregnancy. 
Program level changes 
Safety Changes 
Section 11.2 
Ophthalmology wording updated throughout the 
protocol. Changes in the frequency of 
assessments. The GSK scale removed, steroid 
eye drops not mandatory and corneal images no 
longer required. Updated stopping criteria based 
on ocular examination findings 
Updated in line with program level 
changes. 
Section 11.2 SoA 
tables 
Updated timing of SAE assessments. 
Updated timing of SAE assessments 
in line with program. 
Changes in Assessments and SoAs 
Section 11.2,Table 21, 
Table 22 
CRP assessment removed from SoA tables 
 
Section 11.2 
Removed physical exam and vital sign 
assessment from SoA table of assessments to 
be done regardless of dosing (and updated 
footnote numbering)  
These evaluations are done with 
dosing  
Section 11.2, Table 23 
and 24 
Removed AESI assessment. 
This is covered under AE’s and 
SAEs. This is still being collected. 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 11.2, Table 23 
Clarification around timings for biomarker 
samples. 
Clarifications 
Protocol Clarification and Alignment 
Section 11.6 
Added wording that “Sponsor may decide not to 
evaluate all dose levels based on data external 
to this study…” 
Clarity of wording around when a 
sub-study can be closed 
Section 11.7, Table 26  Infusion timing of belantamab mafodotin and 
GSK’998 (OX40) added 
Regulatory Agency request. Infusion 
timings added 
Section 11.4 
Rationale for combination of belantamab 
mafodotin with GSK’998 (aOX40) preclinical 
wording clarified 
Regulatory Agency request for 
clarified wording 
Section 11.13 
Clarification around wording for the 
administration of GSK’998 only to be 
administered with GSK’916 with the possibility of 
GSK’998 administration 1 day later than 
GSK’916 in the case of an IRR on the date of 
GSK’916 infusion and the maximum treatment 
delay for GSK’998. 
Regulatory Agency request for 
clarified wording 
 
Protocol Amendment 1 (24-JUN-2019) 
The protocol was amended in line with comments from the regulatory agency which 
included the following: 
• 
More preclinical data included to provide the biological rationale for the use of 
belantamab mafodotin in combination GSK’988 (aOX40). 
• 
Lower starting doses for GSK’988 (aOX40). 
• 
Note: belantamab mafodotin is referred to as GSK’916 only for the purposes of 
Laboratory samples. 
• 
Note: GSK’998 (aOX40) is referred to as GSK’998 only for the purposes of 
Laboratory samples. 
 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Revised Study Design 
Section 11. 3 
Rationale for 
combination of 
belantamab mafodotin 
with GSK’998 (aOX40) 
Additional pre-clinical data added, and wording 
clarified 
 Amended to include further details 
regarding the preclinical studies that 
were conducted to support the 
investigation of specific combinations 
in patients with multiple myeloma. As 
requested by the FDA 
Section 11.4 Dose 
justification for 
GSK’998 (aOX40) 
Starting dose of GSK’998 (aOX40) lowered from 
24 mg IV to 8 mg IV Q3W considered equivalent 
to the 0.1 mg/kg dose in the ongoing FTIH trial 
[NCT02528357], assuming a median participant 
weight of 80 kg. 
As requested by the FDA to include a 
lower starting dose 
Section 11.4.1 Clinical 
Activity of GSK’998 
(aOX40) monotherapy 
Added dose of GSK’998 administered. 
As requested by the FDA 
Section 11.5 Dose 
Exploration of 
Combination 
Treatment belantamab 
mafodotin Co-
Administered with 
GSK’998 (aOX40) 
Updated the dose exploration schema for 
belantamab mafodotin in combination with 
GSK’998 (aOX40). 
As requested by the FDA 
Section 11.7.2 
Permitted Dose 
Reductions for 
belantamab mafodotin 
when in combination 
with GSK’998 (aOX40) 
Modified permitted dose reductions for 
belantamab mafodotin when in combination with 
GSK’998 (aOX40) in Table 26 and text. 
Clarification in line with FDA request 
11.7.3 Permitted Dose 
Modifications of 
GSK’998 (aOX40) 
when in combination 
with belantamab 
mafodotin 
Revised text on permitted dose modifications. 
Clarification 
Changes in Assessments and SoAs 
Section 11.1 
Table 19 
Clarified timings 
Added screening thyroid function tests 
Clarification of wording and timings, 
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Section # and 
Name 
Description of Change 
Brief Rationale 
Section 11.1 
Table 20 
Clarified timings/wording 
Clarified AE/SAE timings to agree with text in the 
protocol:  
“AEs will be assessed up to 45 days post the last 
dose. SAEs will be assessed up to 90 days post 
last dose, or 45 days post last dose if the 
participant initiates a new anticancer therapy 
(whichever is shorter). All related SAEs are to be 
collected from first dose through OS follow-up” 
Spot urine (albumin/creatinine ratio) removed 
Clarification of wording and timings 
and removal of tests 
Section 11.1 
Table 21 
Clarified timings/wording of PK, ADA, GSK’916, 
sBCMA samples 
Day 4 Cycle 1 column added for clarity 
“Ocular Examination” removed (to avoid 
confusion, this is carried out every 3 weeks 
regardless of dosing). 
ECOG performance status added  
Deleted reference to EDTA tube & PAXgene 
tube 
Clarification of wording and timings, 
removal/addition of tests and other 
edits for consistency between the 
SoA tables 
 
 
 

SAP_001.pdf: 
Statistical Analysis Plan
Study ID:  208887 Sub-study 1
Official Title of Sub-Study: Platform Sub-study of Belantamab Mafodotin 
(GSK2857916) in Combination with aOX40 (GSK3174998) in Participants with 
RRMM
Date of Document: 24-AUG-2022


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
208887 Sub-study 1 
 
XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021  
Page 1 of _ 
Information Type: 
Statistical Analysis Plan (SAP) 
 
TITLE PAGE 
Protocol Title: 
A Phase I/II, Randomised, Open-label Platform Study Utilising a 
Master Protocol to Study Belantamab Mafodotin (GSK2857916) as 
Monotherapy and in Combination with Anti-Cancer Treatments in 
Participants with Relapsed/Refractory Multiple Myeloma (RRMM). 
Sub-study 1 – Belantamab Mafodotin and aOX40 (GSK3174998) in 
Combination 
 
 
Study Number: 
208887 Sub-study 1  
Compound Number: 
GSK2857916; GSK3174998 
Abbreviated Title: 
Platform Sub-study of Belantamab Mafodotin (GSK2857916) in 
Combination with aOX40 (GSK3174998) in Participants with 
RRMM  
Acronym: 
DREAMM-5 Sub-study 1 
 
Sponsor Name: GlaxoSmithKline Research & Development Limited  
Regulatory Agency Identifier Number(s)  
 
Registry 
 
ID 
IND Number 
EudraCT Number 
 
 
 
 
 
Copyright 2022 the GlaxoSmithKline group of companies. All rights reserved.  Unauthorised 
copying or use of this information is prohibited. 
 


CONFIDENTIAL 
 
XBU Statistical Analysis Plan (SAP) Template v1.0  24 March 2021  
Page 2 of _ 
TABLE OF CONTENTS 
PAGE 
 
1 
TITLE PAGE ................................................................................................................... 1 
TABLE OF CONTENTS .................................................................................................. 2 
1. 
INTRODUCTION ...................................................................................................... 4 
1.1. 
Changes to Protocol Defined Analyses ......................................................... 4 
1.2. 
Objectives, Estimands and Endpoints ........................................................... 4 
1.3. 
Study Design ................................................................................................ 6 
2. 
STATISTICAL HYPOTHESES ................................................................................. 6 
2.1. 
Multiplicity Adjustment .................................................................................. 6 
3. 
ANALYSIS SETS ..................................................................................................... 7 
4. 
STATISTICAL ANALYSES ....................................................................................... 7 
4.1. 
General Considerations ................................................................................ 7 
4.1.1. 
Final Analysis ................................................................................ 7 
4.1.2. 
General Methodology .................................................................... 7 
4.1.3. 
Baseline Definition ......................................................................... 7 
4.1.4. 
Examination of Covariates, Other Strata and Subgroups ............... 7 
4.2. 
Primary Endpoint(s) Analyses ....................................................................... 7 
4.3. 
Secondary Endpoint(s) Analyses .................................................................. 8 
4.3.1. 
Key Secondary Endpoint ............................................................... 8 
4.3.2. 
Secondary Endpoints ..................................................................... 8 
4.4. 
Exploratory Endpoints Analyses ................................................................... 8 
4.5. 
Safety Analyses ............................................................................................ 8 
4.5.1. 
Extent of Exposure ........................................................................ 8 
4.5.2. 
Adverse Events.............................................................................. 9 
4.5.3. 
Other Safety Assessments .......................................................... 10 
4.6. 
Other Analyses ........................................................................................... 11 
4.6.1. 
Pharmacokinetic Analysis ............................................................ 11 
4.6.2. 
Immunogenicity Analysis ............................................................. 11 
4.7. 
Interim Analyses ......................................................................................... 11 
5. 
SAMPLE SIZE DETERMINATION ......................................................................... 11 
6. 
SUPPORTING DOCUMENTATION ....................................................................... 11 
Trademarks ................................................................................................ 12 
 
REFERENCES ....................................................................................................... 13 
7. 
ERROR! BOOKMARK NOT DEFINED. 
 


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Version history  
SAP 
Version 
Approval Date 
Protocol 
Version (Date) 
on which SAP 
is Based 
Change 
Rationale 
SAP 
 
PA5 (21-JAN-
2022) 
Not 
Applicable 
Original version 
 


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1. 
INTRODUCTION 
The purpose of this SAP is to describe the planned analyses to be included in the CSR for 
Study 208887 sub-study 1. For more details about the statistical analysis and plan for the 
overall study refer to the Master SAP. This sub-study was terminated early in the Dose 
Exploration (DE) phase; therefore, this sub-study SAP will focus only on this DE phase.  
1.1. 
Changes to Protocol Defined Analyses 
Effective October 2020, GSK made the decision to close this sub-study at the DE phase. 
The data demonstrate that the participants in the aOX40 sub-study had negligible benefit 
from the combination, which could not be explained by known factors. As a result, all 
analyses corresponding to the Cohort Expansion (CE) phase, as well as the analysis of 
exploratory endpoints will not be performed. 
Changes from the originally planned statistical analysis specified in the protocol are 
detailed in Table 1. 
Table 1 Changes to Protocol Defined Analysis Plan 
Protocol Defined Analysis 
SAP Defined Analysis 
Rationale for Changes 
• Exploratory analyses  
o Biomarker analysis 
• Interim analysis for DE phase 
• All analysis related to CE 
phase  
 
The listed protocol defined 
analyses will not be included 
in this sub-study.  
This sub-study was 
terminated during DE phase 
due to observed lack of 
efficacy.  
 
1.2. 
Objectives, Estimands and Endpoints 
The primary and secondary objectives, along with the corresponding endpoints for Dose 
Exploration are listed in Table 2. 
 
Table 2  Dose Exploration (DE) 
Objectives 
Endpoints 
Primary 
To determine the safety and tolerability of 
belantamab mafodotin in combination with aOX40 
and to establish the recommended Phase 2 dose 
for the combination treatment to explore in the CE 
Phase in participants with RRMM. 
• 
Percentage (number) of participants with 
dose limiting toxicities (DLTs) 
• 
Percent of subjects with AEs, changes in 
clinical signs and laboratory parameters 
 
Key Secondary 


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Objectives 
Endpoints 
To evaluate the clinical measures of efficacy of 
belantamab mafodotin and aOX40 in participants 
with RRMM 
• 
Clinical activity measured as Overall 
Response Rate (ORR) according to the 
International Myeloma Working Group 
(IMWG) Response Criteria (Kumar, et al., 
2016) 
Secondary 
To further evaluate the clinical measures of efficacy 
of belantamab mafodotin and aOX40 in participants 
with RRMM 
Rates of:  
• 
Partial Response (PR);  
• 
Very Good Partial Response (VGPR);  
• 
Complete Response (CR);  
• 
Stringent Complete Response (sCR) 
To describe the exposure of belantamab mafodotin 
when administered in combination with aOX40 in 
participants with RRMM 
• 
Belantamab mafodotin observed 
concentration  
To describe the exposure of aOX40 when 
administered in combination with belantamab 
mafodotin. 
• 
Combination of belantamab mafodotin with 
aOX40 treatment’s observed concentration. 
To assess anti-drug antibodies (ADAs) against 
belantamab mafodotin and against combination 
treatments (biologics) that are administered by IV 
infusion. 
• 
Incidence and titers of ADAs against 
belantamab mafodotin and its combination 
with aOX40, when measured. 
To further determine the safety and tolerability of 
belantamab mafodotin in combination with aOX40 
• 
AEs of special interest for belantamab 
mafodotin  
• 
AEs of special interest for belantamab 
mafodotin in combination with aOX40 
• 
Ocular findings on ophthalmic exam 
 
 
 
 


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1.3. 
Study Design 
Overview of Study Design and Key Features 
Please refer to the 208887 Master SAP for overall Study Design for the study 
Design 
Features 
• Refer to the 208887 Master SAP for the key design feature for the study 
Dosing 
• The Starting Dose (SD) for belantamab mafodotin in study 208887 will be 1.9 mg/kg 
Q3W in combination with aOX40 
• GSK’998 (aOX40) will initially be administered at a flat dose of 8 mg IV Q3W on 
Day 1 of each 21-day cycle after the infusion with belantamab mafodotin. 
 
Dose level 
Belantamab 
mafodotin dose 
GSK’998 (aOX40) 
dose 
1 (starting dose 
level) 
1.9 mg/kg 
8 mg 
2 
2.5 mg/kg 
8 mg 
3 
2.5 mg/kg 
24 mg 
 
Note: Dose level 3 was not initiated in this sub-study due to the study being terminated 
early in the DE phase.  
Time & 
Events 
• Refer to Section 1.3: Schedule of Activities (SoA) in Sub-study 1 modular protocol 
Treatment 
Assignment 
• In DE phase, treatments will be assigned to participants with predefined algorithm.  
Interim 
Analysis 
• The Interim Analysis (IA) planned in the DE will not be carried out.  
Blinding 
• This is an open label study.  
• In DE phase, participants will be assigned to available treatment slots by a 
predetermined algorithmic approach.  
 
2. 
STATISTICAL HYPOTHESES  
In the DE Phase, the primary objective is to determine the safety and tolerability of belantamab 
mafodotin and aOX40. No formal statistical hypothesis will be tested.  
2.1. 
Multiplicity Adjustment 
Analyses of any efficacy endpoints will not be subject to any multiplicity adjustment since each 
sub-study is analysed separately. 


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3. 
ANALYSIS SETS 
Refer to the 208887 Master SAP Section 3 for the complete list of analysis sets for this study. 
4. 
STATISTICAL ANALYSES 
4.1. 
General Considerations 
4.1.1. 
Final Analysis  
GSK decided that no further enrolment will take place on this sub-study. As a result, all analyses 
corresponding to the CE phase, as well as the exploratory endpoints for both the DE and CE 
phase will not be performed.  
The final analyses will be performed after all required database cleaning activities have been 
completed on available DE data and final database release (DBR) and database freeze (DBF) has 
been declared by Data Management. 
4.1.2. 
General Methodology 
Confidence intervals will use 95% confidence levels unless otherwise specified.  
Unless otherwise specified, continuous data will be summarized using descriptive statistics: n, 
mean, standard deviation (std), median, minimum and maximum. Categorical data will be 
summarized as the number and percentage of participants in each category. 
4.1.2.1. 
Study Treatment & Sub-group Display Descriptors 
Phase 
Description 
DE 
1.9mg/kg GSK916+8mg aOX40 
2.5mg/kg GSK916+8mg aOX40 
2.5mg/kg GSK916+24mg aOX40¹ 
¹ Note that this dose level was not used due to early termination 
4.1.3. 
Baseline Definition 
Refer to the Master SAP section 4.1.4 for details on baseline definitions. 
4.1.4. 
Examination of Covariates, Other Strata and Subgroups 
As this sub-study was terminated during the DE phase, covariates, other strata, and subgroups 
are not applicable as these would have been used in the CE phase only.  
4.2. 
Primary Endpoint(s) Analyses 
Primary analysis for the DE phase involves summaries of the number and percentages of 
participants with DLTs and AEs. Both DLTs and AEs will be summarised and listed. All 
analyses for the DE phase will be based on the Safety population, unless otherwise specified.  


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4.3. 
Secondary Endpoint(s) Analyses 
Due to this sub-study being terminated early during the DE phase, there will be no primary 
efficacy analysis for the CE phase as these data were not collected.  
4.3.1. 
Key Secondary Endpoint 
For the definition of the key secondary endpoint, ORR, along with the derivation of confirmed 
response table please refer to Section 4.2.2.1 of the MSAP.  
A summary of investigator assessed best response with confirmation will be produced, using the 
Safety population.  
4.3.2. 
Secondary Endpoints  
Best Overall Response (BOR) rates (i.e Partial Response (PR) rate, Very Good Partial Response 
(VGPR) rate, Complete Response (CR) rate and Stringent Complete Response (sCR) rate) will 
be reported within the summary table described in Section 4.3.1.  
The derivation of confirmed response table in Section 4.2.2.1 of the MSAP, will be used confirm 
the secondary endpoints.  
BOR and corresponding response rates will be summarized using descriptive statistics and listed. 
The corresponding 95% exact CI 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. 
 
Other secondary endpoints, PK, ADAs, and AESIs can be found in the sections below.  
4.4. 
 Exploratory Endpoints Analyses 
Analysis of exploratory endpoints will be performed for neither the DE nor the CE phase, due to 
the early termination of aOX40.  
4.5. 
Safety Analyses 
The safety analyses will be based on the Safety population, unless otherwise specified. Similarly, 
unless otherwise specified, on-treatment AE’s will be reported. 
4.5.1. 
Extent of Exposure 
Refer to the Master SAP Section 4.5.1 for details on the extent of exposure for this study. The 
cycle length term Q3W is equivalent to a cycle length in days of 21 days, to be used in 
calculations for treatment exposure.  
Extent of exposure to belantamab mafodotin monotherapy and combination therapy will be 
summarized. For the combination therapy, extent of exposure will be summarized. 


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A ‘by participant’ summary listing of data on exposure to all study treatments will be produced. 
Dose reductions will be summarised by number of reduction and reasons for reductions. Dose 
delays/interruptions will be summarised by number of delays, and delay duration (days). All the 
dose reductions and dose delays/interruptions will be listed. 
 
4.5.2. 
Adverse Events 
Summaries of all AEs, all drug-related AEs, common non-SAEs, SAEs, and AEs leading to 
permanent discontinuation of study treatment will be reported by system organ class, preferred 
term and maximum grade.  
Listings of all AEs, fatal SAEs, non-fatal SAEs, reasons for considering as a SAE and AEs 
leading to permanent discontinuation will be reported.  
Dose limiting toxicities (DLTs) will also be summarised and listed.  
 
4.5.2.1. 
Adverse Events of Special Interest 
The list of terms and reporting requirements for GSK AESI, and the known list of AESIs for 
GSK’998 can be found in section 8.3.10 of the Sub-Study 1 protocol.  
A summary of corneal events by grade will be provided using the GSK scale for all those 
participants who has an event under protocol amendment 1; using CTCAE scale for all those 
participants who had an event under protocol amendment 2, and using KVA scale for those 
patients who had an event under protocol amendment 4. Corresponding listings for ocular events 
will also be reported, along with a listing of visual acuity by grade. 
The grading scales for the GSK and KVA scale for corneal events can be found in Table 6 and 
Table 7 in the MSAP respectively. For guidance of grading based on changes in visual acuity 
refer to Table 8 in the MSAP.  
4.5.2.1.1. Inmune-related Adverse Events (irAEs) 
irAEs will be graded by the investigator according to the National Cancer Institute-Common 
Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5. irAE will be coded using 
the standard Medical Dictionary for Regulatory Affairs (MedDRA dictionary, version 25.0) and 
grouped by SOC. 
A summary of all immune-related adverse events by system organ class, preferred term and 
maximum grade, and a listing containing all immune-related adverse events will be produced.  


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4.5.2.2. 
COVID-19 Assessment and COVID-19 AEs 
A Standardised MedDRA Query (SMQ) will be used to identify all COVID-19 AEs.  
The impact of COVID-19 on DLTs during the DE phase of any sub-study will be monitored 
during the study conduct through review of protocol deviations. DLTs will be reported according 
to the DLT evaluable population in Section 3 of the MSAP.  
The incidence of AEs and SAEs (Fatal and Non-Fatal) of COVID-19, COVID-19 AEs leading to 
study drug discontinuation, and COVID-19 AEs leading to study withdrawal, and COVID-19 
AEs by severity, will be obtained from standard AE and SAE summaries and listings. 
 
4.5.2.3. 
Deaths and Serious Adverse Events 
Refer to Section 4.5.2.4 of the MSAP. 
4.5.2.4. 
Adverse Events Leading to Discontinuation of Study Treatments and Other 
Significant Adverse Events  
The following categories of AEs will be summarized separately by individual treatment 
component and combination (belantamab mafodotin monotherapy and GSK’998 (aOX40) + 
belantamab mafodotin) as collected in descending order of total incidence by SOC and PT and 
separate supportive listings will be generated with participant level details for those participants: 
• 
AEs Leading to Permanent Discontinuation of Study Treatment  
• 
AEs Leading to Dose Interruptions or Delays  
• 
AEs Leadings to Dose Reductions  
4.5.2.5. 
Pregnancies 
Refer to Section 4.5.2.6 of the Master SAP.  
4.5.2.6. 
Clinical Laboratory Analysis 
Refer to Section 4.5.2.7 of the MSAP for more details on the clinical laboratory analysis 
including the analysis of liver function tests.  
Summaries of chemistry changes from baseline, hematology changes from baseline, and 
hematology/chemistry results by maximum grade increase post-baseline relative to baseline will 
be produced. Supporting listings of laboratory data and urinalysis data for participants with any 
value of potential clinical importance will be provided.  
4.5.3. 
Other Safety Assessments 
The analyses of non-laboratory safety test results including ECGs and vital signs will be based 
on GSK Core Data Standards, unless otherwise specified. LVEF and Performance status will be 
summarized and listed based on GSK Oncology Data Standard. The details of the planned 


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displays are presented in the OPS document. For more detail please refer to Section 4.5.3 of the 
Master SAP.  
4.6. 
Other Analyses 
No POPPK, exploratory biomarker, or PD analyses will be conducted. For this sub-study there 
will also be no health-related quality of life analysis due to early termination. 
4.6.1. 
Pharmacokinetic Analysis 
PK samples will be collected for belantamab mafodotin and/or aOX40 in Cycle 1 as well as later 
cycles as indicated in the SoA tables of protocol. PK analyses will be done for each analyte 
measured in the DE phase, as data permit. For more details on these analyses refer to the Master 
SAP Section 4.6.1.  
4.6.2. 
Immunogenicity Analysis 
Refer to section 4.6.5 of the Master SAP for more details on the analysis of incidence and titers 
of ADAs against belantamab mafodotin and its combination with aOX40, when measured. 
4.7. 
Interim Analyses 
The planned interim analysis can be found in more detail in Section 4.7 of the Master SAP.  
An interim analysis for ORR would have been performed at the end of the DE phase, after 10 
participants had been treated. However, due to the early termination of this sub-study neither of 
the 2 dose levels explored in this sub-study reached the 10-participant goal. Hence, no interim 
analysis will be performed.  
5. 
SAMPLE SIZE DETERMINATION 
In the DE phase, approximately up to 10 participants will be assigned to the combination dose 
level. However, the study was terminated early due to lack of efficacy; therefore only 6 
participants were enrolled onto dose 1 and 3 participants were enrolled onto dose 2.  
 
6. 
SUPPORTING DOCUMENTATION 
For supporting documentation for this overall study please refer to Section 6 of the Master SAP 
for more details.  
 
 


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Trademarks 
Trademarks of the GlaxoSmithKline Group 
of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
Blenrep 
 
MedDRA 
 
 
 


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7. 
REFERENCES     
Kumar, S., Paiva, B., Anderson, K. C., Durie, B., Landgren, O., Moreau, P., ... & Avet-Loiseau, 
H. (2016). International Myeloma Working Group consensus criteria for response and minimal 
residual disease assessment in multiple myeloma. The lancet oncology, 17(8), e328-e346.