Clinical trial NCT06655818
Conditions: Relapsed/Refractory Multiple Myeloma
Sponsor: GlaxoSmithKline
Start date: 2021-03-09; Completion date: 2024-02-14
Enrollment: 4 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 a sub study of the Master protocol (NCT04126200).

Detailed description:

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

Protocol documents:
Prot_000.pdf: 
Protocol Amendment 5
Study ID:  208887 Sub Study 4
Official Title of Sub Study 4: 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 
4 
- 
Belantamab Mafodotin and Dostarlimab (GSK4057190) in Combination
NCT ID of Sub Study 4: NCT06655818
Date of Document: 21-Jan-2022
NCT ID of Master Protocol: NCT04126200


TMF-13844075 
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Protocol Amendment 05 
GlaxoSmithKline group of companies 
 
208887 Sub-study 4 
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 4 – Belantamab mafodotin and 
Dostarlimab (GSK4057190) in Combination 
Protocol Number: 208887 Sub-study 4 / Amendment 05 
Compound Number 
or Name: 
Belantamab mafodotin (GSK2857916), dostarlimab 
(GSK4057190) 
Study Phase: I/II 
Brief Title: Sub-study of belantamab mafodotin (GSK2857916) as monotherapy and in 
combination with dostarlimab (GSK4057190) in participants with RRMM 
Acronym: DREAMM 5 Sub-study 4 
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 
 
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: 21-Jan-2022 
Copyright 2022 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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SPONSOR SIGNATORY: 
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 4 – Belantamab mafodotin and 
Dostarlimab (GSK4057190) in Combination 
Protocol Number: 208887 Sub-study 4 / Amendment 05 
Compound 
Number: 
Belantamab mafodotin (GSK2857916) 
 
 
 
 
 
 
 
 
Brandon Kremer, MD, PhD 
Clinical Development Leader 
 
Date 
 
The signed page is a separate document. 
 
 
Medical Monitor Name and Contact Information is provided on the protocol title page  


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
DNG Number 
Amendment 05  
21-Jan-2022 
TMF-13844075 
Amendment 04 (Sub-study 4) 
14-DEC-2020 
2020N453224_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 05 (Sub-study 4): 21-Jan-2022 
Overall Rationale for the Amendment: 
Changes listed in the table below are for the Sub-study 4 protocol only. Changes for 
Protocol Amendment 5 that are related to the 208887 Master Protocol and specific sub-
studies are tabulated at the beginning of each relevant Sub-study module. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Throughout 
document 
Updated reference to GSK2857916/ 
belantamab mafodotin Investigator’s 
Brochure 
To refer to the most recent version of the IB 
Minor editorial and document formatting 
revisions 
To improve overall clarity and typographical 
corrections 
Renumbering of Tables and Footnotes  
As a result of changes within the document  
For more information of certain sections 
mentioned the reference to master 
protocol 
To align with program level updates and for clarity 
1.3. Schedule of 
Activities (SoA) 
Added multiple gated acquisition 
(MUGA) scan 
Clarified text for the Treatment Period for 
belantamab mafodotin and dostarlimab 
for DE and CE phase, for performing the 
same procedure (ECHOs or MUGA 
scans for LEVF) used at screening 
throughout the study, and during end of 
treatment (EoT) and Follow-up 
Updated in line with cardiac monitoring 
requirements across belantamab mafodotin 
program, based on emerging safety data 
Updated guidance on bone marrow/core 
biopsy sample collection 
To clarify language 
Updated text to reflect the serum protein 
electrophoresis (SPEP) to be performed 
at Q3W and the urine protein 
electrophoresis [UPEP]) to be performed 
to confirm objective response (PR or 
better) or if there is concern for disease 
progression, during the Treatment 
Period. 
Clarified the text suggesting the Serum 
Immunofixation to be perfumed when 
SPEP or UPEP are negative; and 
performed to confirm objective response 
(PR or better). 
To clarify language 
Removed the single vital signs 
assessment on Day 4 (Cycle 1 only), 
Day 8 (Cycles 1-6) and Day 15 (Cycles 1 
and 2). 
To reduce patient burden 
 
Added additional procedures for 
participants who were HBcAb positive 
during screening 
Added Table 7 for additional procedures 
for participants with a history of 
Hepatitis B 
To align with the latest regulatory guidance 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Revised the ocular exam follow-up time 
period for participants with a treatment-
related change in vision at the end of 
treatment visit from every 6 weeks to 
every 3 months 
To align with program level updates  
Removed biomarker assessments 
To reduce patient burden 
Removed PK and ADA assessments 
(Also removed previous Table 7 
Pharmacokinetic and ADA- Belantamab 
mafodotin and Dostarlimab; sBCMA 
blood sampling times) 
To reduce patient burden 
Section 2.3. 
Benefit/Risk 
Assessment 
For more information of benefit and risk 
of belantamab mentioned reference to IB 
and master protocol 
To clarify language 
Section 4.1 
Overall Design 
Removed Previous Table 9 “Dose 
Exploration Schema- Belantamab 
mafodotin in combination with 
Dostarlimab (GSK’190)” 
To clarify language 
Section 6.2 
Administration of 
Belantamab 
mafodotin and 
Dostarlimab 
Updated the text for belantamab 
mafodotin administration 
To clarify language 
Section 10 
References 
Some new references were added and 
some references were updated 
Addition and update of references were because 
of changes in the main text. 
Appendix 11 
Decentralized and 
Remote 
Assessment 
Approaches 
Updated the heading from ‘Home 
Healthcare and Telemedicine 
Approaches’. 
To align with Master protocol 
Appendix 12. 
Abbreviations and 
Trademarks 
Updated the new abbreviations used in 
the document. 
To reflect new changes  
Appendix 13: 
Protocol 
Amendment 
History 
Addition of summary of changes from 
amendment 04 in the appendix as per 
the template requirement 
Template alignment  


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TABLE OF CONTENTS 
PAGE 
TITLE PAGE ................................................................................................................... 1 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3 
TABLE OF CONTENTS .................................................................................................. 6 
1. 
PROTOCOL SUMMARY .......................................................................................... 9 
1.1. 
Synopsis ....................................................................................................... 9 
1.2. 
Schema ...................................................................................................... 10 
1.3. 
Schedule of Activities (SoA) ........................................................................ 10 
2. 
INTRODUCTION .................................................................................................... 25 
2.1. 
Rationale for Combination of Belantamab mafodotin with 
Dostarlimab ................................................................................................ 25 
2.2. 
Background for Dostarlimab........................................................................ 28 
2.2.1. 
Clinical Experience ...................................................................... 28 
2.2.2. 
Pharmacokinetic Summary .......................................................... 30 
2.2.3. 
Safety .......................................................................................... 31 
2.3. 
Benefit/Risk Assessment ............................................................................ 32 
2.3.1. 
Risk Assessment ......................................................................... 32 
2.3.2. 
Benefit Assessment ..................................................................... 34 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 34 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 35 
4. 
STUDY DESIGN .................................................................................................... 35 
4.1. 
Overall Design ............................................................................................ 35 
4.2. 
Scientific Rationale for Study Design .......................................................... 35 
4.3. 
Justification for Dose .................................................................................. 35 
4.4. 
Participant Completion and End of Study Definitions .................................. 36 
4.4.1. 
Participant Completion Definitions: .............................................. 36 
4.4.2. 
Study Completion: ....................................................................... 36 
5. 
STUDY POPULATION ........................................................................................... 36 
5.1. 
Inclusion Criteria for Participants ................................................................ 37 
5.2. 
Exclusion Criteria ........................................................................................ 37 
5.3. 
Lifestyle Considerations .............................................................................. 37 
5.4. 
Screen Failures........................................................................................... 37 
6. 
STUDY INTERVENTION ........................................................................................ 37 
6.1. 
Study Intervention(s) Administered ............................................................. 37 
6.2. 
Administration of Belantamab mafodotin and Dostarlimab .......................... 38 
6.3. 
Preparation/Handling/Storage/Accountability .............................................. 40 
6.4. 
Measures to Minimize Bias: Randomization and Blinding ........................... 40 
6.5. 
Concomitant Therapy.................................................................................. 40 
6.6. 
Dose Modification ....................................................................................... 40 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
WITHDRAWAL FROM THE STUDY ...................................................................... 41 


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7.1. 
Discontinuation of Study Intervention .......................................................... 41 
7.2. 
Participant Withdrawal from the Study ........................................................ 41 
7.3. 
Lost to Follow Up ........................................................................................ 41 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 41 
8.1. 
Efficacy Assessments ................................................................................. 41 
8.2. 
Safety Assessments ................................................................................... 41 
8.3. 
Adverse Events and Serious Adverse Events ............................................. 41 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 41 
8.3.2. 
Method of recording AE and SAE information .............................. 41 
8.3.3. 
Method of Detecting AEs and SAEs ............................................. 41 
8.3.4. 
Follow-up of AEs and SAEs ......................................................... 42 
8.3.5. 
Reporting of Potentially Life-Threatening AEs to the GSK 
Medical Director ........................................................................... 42 
8.3.6. 
Regulatory Reporting Requirements for SAEs ............................. 42 
8.3.7. 
Management of Pregnancy .......................................................... 42 
8.3.8. 
Cardiovascular and Death Events ................................................ 42 
8.3.9. 
Disease-Related Events and/or Disease-Related 
Outcomes Not Qualifying as SAEs............................................... 42 
8.3.10. 
Adverse Events of Special Interest .............................................. 42 
8.4. 
Treatment of Overdose ............................................................................... 42 
8.5. 
Pharmacokinetics ....................................................................................... 43 
8.6. 
Genetics ..................................................................................................... 43 
8.7. 
Immunogenicity Assesments ...................................................................... 43 
8.8. 
Biomarkers ................................................................................................. 43 
8.9. 
Health-Related Quality of Life ..................................................................... 43 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 43 
9.1. 
Statistical Hypotheses................................................................................. 43 
9.2. 
Sample Size Determination ........................................................................ 43 
9.3. 
Populations for Analyses ............................................................................ 43 
9.4. 
Statistical Analyses ..................................................................................... 43 
9.5. 
Interim Analysis .......................................................................................... 43 
9.6. 
Sample Size Sensitivity ............................................................................... 43 
10. REFERENCES ....................................................................................................... 44 
11. GUIDELINES FOR DOSE MODIFICATION AND OTHER PARTNER 
COMBINATION TREATMENTS FOR ALL SUBSTUDIES ...................................... 48 
12. APPENDICES: SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 49 
12.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 49 
12.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 50 
12.3. 
Appendix 3: AEs: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ......................................................... 51 
12.4. 
Appendix 4: ECOG Performance Status ..................................................... 52 
12.5. 
Appendix 5: NYHA Functional Classification System .................................. 53 
12.6. 
Appendix 6: Modified Diet in Renal Disease ............................................... 54 


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12.7. 
Appendix 7: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................. 55 
12.8. 
Appendix 8: Genetics .................................................................................. 56 
12.9. 
Appendix 9: Liver Safety: Required Actions and Follow-up 
Assessments and Study Treatment Rechallenge Guidelines ...................... 57 
12.10. Appendix 10: Eye Care Specialist- Qualifications and Requirements .......... 58 
12.11. Appendix 11: Decentralized and Remote Assessment Approaches ............ 58 
12.12. Appendix 12: Abbreviations and Trademarks .............................................. 59 
12.13. Appendix 13: Protocol Amendment History ................................................. 65 
 


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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 4 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 4-specific Content 
Section 
Heading title 
Brief description of content 
1.3 
Schedules of Activities 
Comprehensive SoA tables specific for Sub-study 4 
2.1 
Rationale for Combination of 
Belantamab mafodotin with 
Dostarlimab (GSK4057190) 
Explanation why treatment with belantamab 
mafodotin and dostarlimab is expected to be 
complementary 
2.2 
Background for Dostarlimab 
(GSK4057190) 
Available data on clinical pharmacology, safety and 
clinical activity 
2.3 
Benefit/Risk Assessment 
Risk assessments for dostarlimab treatment; benefit 
assessment summary 
4.1 
Overall Design 
Description of dose escalation design for the 
combination treatment  
4.3 
Justification for Dose 
Data for the basis of the planned dostarlimab dosing 
5.2 
Exclusion Criteria 
Three additional exclusion criteria were defined for 
Sub-study 4 
6.1 
Study Intervention(s) 
Administered 
Specifications for belantamab mafodotin and 
dostarlimab IP 
6.2 
Administration of Belantamab 
mafodotin and Dostarlimab 
Specifications for administration of belantamab 
mafodotin and dostarlimab 
6.6 
Dose Modification 
Detailed directions guidance for dose modifications 
of combination treatment 
8.3.7 
Management of Pregnancy 
Timeframes for on data collection 
8.3.10 
Adverse Events of Special 
Interest 
Information on dostarlimab AESI 
8.4 
Treatment of Overdose 
Guidance for potential drug overdose for 
dostarlimab 
8.8 
Biomarkers 
Summary of the biomarker research being 
conducted for sub-study 4 
12.13 
Appendix 13: Protocol 
Amendment History 
Summary of Changes Tables for Sub-study 4 
specific amendments 
 
1.1. 
Synopsis 
Protocol Title:  A PhaseI/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 4 – Belantamab mafodotin and 
Dostarlimab (GSK4057190) in Combination 


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Belantamab mafodotin causes auristatin-induced immunogenic cell death (ICD) on target 
multiple myeloma (MM) tumor cells and therefore, belantamab mafodotin is a good 
candidate for combining with immune checkpoint inhibitors. 
Many tumors, including MM, use various escape mechanisms to evade immune control 
and promote tumor growth.  One of those mechanisms is the expression of PD-1 ligands 
(PD-L1). Recent advances in cancer treatment include successful checkpoint blockade by 
using antibodies binding to PD-1 or PD-L1.  The anti-PD-1 and anti-PD-L1 antibodies 
have a favorable safety profile and have resulted in durable responses in a variety of 
cancers, including melanoma, kidney cancer, lung cancer, and Hodgkin lymphoma.  The 
agents continue to be evaluated in various solid tumors and hematological malignancies, 
alone or in combination with other therapies.  There is also a growing body of data 
demonstrating broad expression of PD-1 and its ligands in the microenvironment of MM, 
indicating an important role of the PD-1 pathway.  Although thus far, anti-PD-1 treatment 
alone has not been effective in MM, there is a recent report of a stringent Complete 
Response (sCR; ongoing for 27 months at time of publication) achieved in a patient with 
high-risk smoldering MM following pembrolizumab monotherapy. 
Based on the scientific rationale of checkpoint blockade combination with agents such as 
belantamab mafodotin, which leads to ICD, the GSK205207 combination clinical trial of 
belantamab mafodotin and pembrolizumab in patients with RRMM initiated enrollment 
and there have been no safety concerns towards pembrolizumab in 12 treated patients. 
This Sub-study will evaluate the safety and anti-myeloma activity of belantamab 
mafodotin in combination with GSK’s PD-1 inhibitor dostarlimab (GSK4057190).  
Evidence to date does not indicate that overlapping toxicities would be expected between 
belantamab mafodotin and dostarlimab. 
The starting dose of belantamab mafodotin will be 1.9 mg/kg to be evaluated in Dose 
Level 1, with the highest dose of Belamaf of 2.5 mg/kg planned for dose level 2.  The 
dose of dostarlimab will be identical across the dose level groups and will be 500 mg 
Q3W for 4 cycles followed by 1000 mg Q6W for subsequent cycles. 
1.2. 
Schema 
Please refer to the 208887 MP. 
1.3. 
Schedule of Activities (SoA) 
• 
The timing and number of planned study assessments (including safety, 
pharmacokinetic, biomarker or other 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 of study treatments administered) to ensure appropriate 
monitoring. 
• 
Note: belantamab mafodotin is referred to as GSK’916 and dostarlimab is referred to 
as GSK’190 only for the purposes of Laboratory assessments and samples. 
 


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Table 2 
SoA – Screening for Dose Expansion and Cohort Expansion Phases: Belantamab Mafodotin + Dostarlimab  
Screening Study Assessments1 
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 Assessments do not need to be repeated at C1D1 unless otherwise specified.  All other assessments can be done ≤3 days prior to 
treatment unless otherwise specified.  If C1D1 Hem/Chem results are below eligibility threshold required at Screening, GSK Medical Director to be contacted for review 
prior to dosing. 
Informed Consent 
X 
1. 
Screening/baseline ocular examination will be performed by a qualified eye-care specialist 
(ophthalmologist/optometrist, see 208887 MP Appendix 10) 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. 
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 C1D1and the second test within 
72 hours prior to administration of C1D1.   
3. 
Refer to the 208887 MP Appendix 2 for a comprehensive list of lab tests that must be collected for all 
participants. 
4. 
eGFR as calculated by MDRD formula (208887 MP Appendix 6) 
5. 
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). 
6. 
Complete at screening or within 12 weeks prior to C1D1. 
7. 
If a participant tested hepatitis B core antibody positive, refer to Table 7 for additional procedures 
throughout the study. Hep C RNA testing is optional, but it may be performed to determine participant 
eligibility if Hep C antibody positive. If negative, participant is eligible (see exclusion criteria 12) for 
details). 
8. 
Single ECG at Screening. 
9. 
ECHO or MUGA scan for LVEF may be performed at baseline or within 30 days of C1D1. 
10. SPEP and UPEP will include M protein levels. 
11. Serum Free Light Chain assay will include kappa/lambda ratio and quantification of involved and 
uninvolved light chains. 
12. 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. 
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 for 
maintaining adequate urinary output (208887 
MP 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 
Haematology 
X3 
Clinical chemistry  
X3 
Estimated Glomerular Filtration Rate (eGFR) 
X4 
Urinalysis (dipstick) OR Spot Urine 
(albumin/creatinine ratio) 
X5 
HBsAg7, HBcAb7, HCV tests7 
X6,7 
12 Lead ECG 
X8 
ECHO or MUGA scan LVEF 
X9 


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Screening Study Assessments1 
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 Assessments do not need to be repeated at C1D1 unless otherwise specified.  All other assessments can be done ≤3 days prior to 
treatment unless otherwise specified.  If C1D1 Hem/Chem results are below eligibility threshold required at Screening, GSK Medical Director to be contacted for review 
prior to dosing. 
Screening Disease Evaluation 
 
13. In participants with known or suspected extramedullary plasmacytoma, a whole-body scan (i.e., CT, 
MRI, or PET-CT) may be performed within 30 days prior to C1D1.  The same method should be used 
throughout the study (i.e., if a PET-CT scan was used as baseline scan then participant 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. 
14. Only required for participants with IgD/IgE myeloma. 
15. Please refer to Table 6 for scheduled BM collection procedures to include aspirate and biopsy.  
16. If FISH testing cannot be performed at a local lab the samples can be sent to the central lab. 
 
Beta-2 microglobulin 
X 
UPEP 24 hr urine collection 
X10 
Urine immunofixation 
X 
SPEP 
X10 
Serum Immunofixation 
X 
Serum FLC assay 
X11 
IgG, IgM, IgA 
X 
IgD or IgE, if applicable 
X14 
Calcium corrected for albumin (serum) 
X 
Skeletal Survey 
X12 
Extramedullary Plasmacytoma Assessment 
(by whole body CT or whole body MRI or 
CT/PET) 
X13 
Bone Marrow (BM) Aspiration/Biopsy 
BM aspirate and/or core biopsy for local 
disease assessment  
X15 
BM aspirate for FISH testing  
X16 
ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; D1 = Day 1, etc.; CK = creatinine kinase;  CRP = C-reactive protein; CT = 
computed tomography; ECG = electrocardiogram; eGFR = estimated glomerular filtration rate; EM = extramedullary;  EOI = End of Infusion; FLC = free light chain; IgD/IgE = 
Immunoglobulin D or E; LVEF = left ventricular ejection; MDRD = Modified Diet in Renal Disease; MP = Master Protocol; MRI = magnetic resonance imaging; MUGA = multiple gated 
acquisition; PET = positron emission tomography; PFS = progression-free survival; PD = progressive disease; PK = pharmacokinetics; QID = 4 times a day; RRMM = 
relapsed/refractory MM; sBCMA = soluble B cell maturation antigen; 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 Regardless of Dosing: Belantamab Mafodotin + Dostarlimab  
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.  
• 
From Dose 2, assessments can be delayed or brought forward by a maximum of 5 days to be aligned with the next dosing date. If administration of study treatment is 
delayed ≤7 days, assessments indicated to occur at the dosing visit can be scheduled to occur when dosing occurs. If administration of study treatment is delayed >7 
days, assessments indicated at the dosing visit are to be performed at the next expected weekly visit. 
• 
All assessments from Dose 2 can be performed ≤3 days prior to the scheduled date unless otherwise specified. 
Adverse Events1 
Ongoing  
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 70 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  
2. 
Informed consent for optional sub studies (e.g. genetic research) must be obtained before collecting 
a sample. The sample will be collected on C1D1prior to infusion. 
3. 
On study ocular exams to be performed by a qualified eye-care specialist (see 208887 MP 
Appendix 10) 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 Section 208887 MP Section 8.2.7 for list of 
ophthalmic exam procedures. If there are no significant KVA Grade 2 or above) treatment 
related  ocular examination findings ocular 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 h prior to the dose, this assessment does not need to be repeated on Day 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 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 ≥2+, or with positive protein if 
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 
Haematology (CBC) 
X4 
X4 
Clinical chemistry 
X4 
X4 
eGFR5 
X 
X 
Urinalysis (dipstick) OR Spot 
Urine (albumin/creatinine 
ratio) 
X6 
X6 
ECHO or MUGA scan for 
LVEF 
 
X7 
Disease Evaluation (every 3 weeks even if a dose is delayed) 
UPEP 24 hr urine collection  
 
X8 


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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.  
• 
From Dose 2, assessments can be delayed or brought forward by a maximum of 5 days to be aligned with the next dosing date. If administration of study treatment is 
delayed ≤7 days, assessments indicated to occur at the dosing visit can be scheduled to occur when dosing occurs. If administration of study treatment is delayed >7 
days, assessments indicated at the dosing visit are to be performed at the next expected weekly visit. 
• 
All assessments from Dose 2 can be performed ≤3 days prior to the scheduled date unless otherwise specified. 
Urine immunofixation 
 
X9 
urine dipstick protein quantification is not available. Albumin/creatinine will be performed at a local 
lab (first void). 
7. 
ECHOs or MUGA scans for LEVFto be done if clinically indicated. The same procedure used at 
screening should be used throughout the study.  
8. 
SPEP must be performed Q3W. UPEP must be performed to confirm objective response (PR or 
better) or if there is concern for disease progression. 
9. 
To be performed when SPEP and UPEP are negative. Also to be performed to confirm objective 
response (PR or better).  
10. Serum Free Light Chain assay will include kappa/lambda ratio and quantification of involved and 
uninvolved light chains; to be done every 3 weeks. 
11. Only required for participants with IgD/IgE myeloma 
12. Skeletal Survey (at the time of suspected disease progression or as clinically 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  
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. Please refer to Table 6 for scheduled BM collection procedures to include aspirate and biopsy.  
16. Assessed in CE Phase only. 
17. OSDI will be performed at C1D1, at or directly after C4D1 and at EOT only. Additional assessments 
may be conducted for those participants who are experience a worsening in visual function. 
18. Collected pre-dose Q6W from Cycle 1 until EOT. 
SPEP 
 
X8 
Serum Immunofixation 
 
X9 
Serum FLC assay 
 
X10 
IgG, IgM, IgA 
 
X 
IgD or IgE 
 
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 sCR 
 
Once after CR or sCR14 
Bone Marrow (BM) Aspiration/Biopsy 
BM aspirate and/or core 
biopsy for local Disease 
assessment 
 
X15 
BM core biopsy to assess 
sCR (local)  
 
X15 
Health Outcomes17 
PRO-CTCAE 
X 
X 
OSDI 
X17 
 X17 
EORTC QLQ-C30 and 
EORTC IL52 
X18 
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AE = Adverse Event; ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; D1 = Day 1, etc.; CK = creatinine kinase;  CRP = C-reactive 
protein; 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; MDRD = Modified Diet in Renal Disease; MP = Master Protocol; MRI = 
magnetic resonance imaging; MUGA = multiple gated acquisition; NEI-VFQ-25 = National Eye Institute Visual Functioning Questionnaire 25; 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; QID = 4 times a day; RRMM = relapsed/refractory MM; SAE = Serious Adverse Event; SOI = start of infusion; SPEP = serum protein 
electrophoresis; UPEP = urine protein electrophoresis 


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Table 4 
SoA –Treatment Period on Dosing Days or After Dosing Only: Regarding Belantamab Mafodotin + Dostarlimab  
Study Assessments 
Cycle 1 Day 
1 (Week 1) 
Cycle 1 
Day 8 
Day 15 
Cycle 2 to EoT 
 
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 dose unless otherwise specified. From Dose 2, assessments can be delayed or brought forward by a 
maximum of 5 days to be aligned with the next dosing date. If administration of study treatment is delayed ≤7 days, assessments indicated to occur at the dosing visit can be 
scheduled to occur when dosing occurs. If administration of study treatment is delayed >7 days, assessments indicated at the dosing visit are to be performed at the next expected 
weekly visit. 
If C1D1 Hem/Chem results are below eligibility threshold required at Screening, GSK Medical Director to be contacted for review prior to dosing. 
Safety 
1. 
Measured after resting for at least 5 minutes. For the first infusion, vital 
signs must be monitored for each study drug infusion at: pre-dose (within 
30 min prior to SOI); at the end of infusion (EOI) (+0-10 min); and 1 hr 
post EOI (+0-10 min). For subsequent infusions, vital signs must be 
monitored for each study drug infusion: at pre-dose (within 30 min prior to 
SOI); at EOI (+0-10 min), and 30 min post EOI (+0-10 min) and as 
clinically indicated. 
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. 
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). 
4. 
If completed within 72 hours prior to the dose, this assessment does not 
need to be repeated on Day 1 of each Cycle. CBC may be done more 
frequently as clinically indicated. Refer to 208887 MP Appendix 2 for 
comprehensive list. 
5. 
eGFR as calculated by MDRD formula (208887 MP Appendix 6). 
6. Please refer to 208887 MP Section 6.6.3 of the protocol for guidance on 
dose delays, reduction and modification. The next scheduled dose must 
be administered every 21 days (Q3W) or 42 days (Q6W) (+3-day window) 
since prior/last dose and cannot be given sooner/more frequently than 
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 
Weight 
X 
 
X 
ECOG Performance 
Status 
X 
 
X 
Pregnancy Test  
X2 
 
X2 
Troponin 
 
 
X 
Urinalysis (dipstick) OR 
Spot Urine (albumin / 
creatinine ratio) 
X3 
 
X3 
Hematology (CBC) 
X4 
X4 
X4 
Clinical Chemistry 
X4 
X4 
X4 
eGFR 
X5 
X5 
X5 
Treatment with Belantamab Mafodotin 
Administration of 
belantamab mafodotin  
X 
 
Day 1 of each dose6 
Premedication if needed 
X 
 
X (at the start of each dose)7 
Treatment prophylaxis and 
management of 
X8 
 
X8 


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preservative-free artificial 
tears and cooling masks 
this. If in the judgment of the Investigator, treatment needs to be initiated 
prior to the next planned scheduled dose following a dosing delay and 
where clinical toxicity has resolved, please discuss with the Medical 
Director.Please see Section 6.2. All assessments should remain on 
schedule with the exception of those associated with dosing. Belantamab 
Treatment with Dostarlimab 
Administration of 
dostarlimab9 
X10,11 
 
Day 1 of each dose10,11 


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mafodotin will be administered as an IV infusion (see Section 6.1 for 
details).  
7. Premedication should be considered in any participant who experienced 
an infusion related reaction at first or any subsequent infusion with 
belantamab mafodotin or dostarlimab combination see relevant sub-study 
Section 6.2. 
8. 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 indicated per the discretion of thea qualified eye-care 
specialist (see 208887 MP Appendix 10). 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. 
9. Administration to occur minimum one hour after completion of infusion of 
belantamab mafodotin. Dostarlimab to be administered as IV infusion at 
prescribed flat dose over 30 minutes. A window of +3 days is acceptable 
for both for Q3W and Q6W dosing schedule. If in the judgment of the 
Investigator, belantamab mafodotin and dostarlimab combination 
treatment needs to be initiated prior to the next planned scheduled dose 
following a dosing delay and where clinical toxicity has resolved, please 
discuss with the Medical Director.  
10. Note: If belantamab mafodotin is held or discontinued for any toxicity, 
dostarlimab is also to be held or discontinued. 
11. Dosing Schedule (Section 6.2): 500 mg every 3 weeks for the first 4 
doses, followed by then 1000 mg every 6 weeks  


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ALP = alkaline phosphatase; BCVA = best corrected visual acuity; BNP = B-type natriuretic peptide; D1 = Day 1, etc.; CK = creatinine kinase;  CRP = C-reactive protein; 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; MDRD = Modified Diet in Renal Disease; MP = Master Protocol; MRI = magnetic 
resonance imaging; NEI-VFQ-25 = National Eye Institute Visual Functioning Questionnaire 25; 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; QID 
= 4 times a day; RRMM = relapsed/refractory MM; SOI = start of infusion; SPEP = serum protein electrophoresis; UPEP = urine protein electrophoresis 
 


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Table 5 
SoA: EoT and Follow-up for Belantamab Mafodotin + Dostarlimab Sub-Study 
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 up to 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 for at least 70 days after the last dose of study treatment and immune-
related AEs/SAEs will be collected up to 70 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. Concomitant 
medications administered after the EoT visit should be recorded when given for SAEs/AESIs as 
defined in Section 8.3 and 208887 MP Section 8.3. 
5. 
End of treatment ophthalmic exam to be performed by an eye-care specialist. See 208887 MP 
Section 8.2.7 for list of exams. 
6. 
Participants with a treatment-related corneal exam findings, ocular symptoms and/or change in 
vision at the End of Treatment Visit will be followed every 3 months (7 days), or more frequently if 
clinically indicated, until return to baseline, deemed clinically stable by the qualified eye-care 
specialist (see Appendix 10 Section 12.10), 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. 
Pregnancy test (serum or urine) must be performed in women of childbearing potential at EoT and 
90 days (±7 days) after last dose of study treatment. A follow up pregnancy assessment by 
telephone (for WOCBP only) should be performed 4 months after the last dose of study treatment  
9. 
eGFR as calculated by MDRD formula (208887 MP Appendix 6). 
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 or MUGA scan 
for LVEF 
X11 
 
 
Disease Evaluation every 3 weeks2 
UPEP 24 hr urine 
collection  
X 
X12 
 
Urine immunofixation 
X 
X12 
 
SPEP 
X 
X12 
 
Serum Immunofixation 
X 
X12 
 
Serum FLC assay 
X 
X12 
 
IgG, IgM, IgA 
X 
X 
 
IgD or IgE 
X13 
X13 
 


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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. 
Calcium corrected for 
albumin (serum) 
X 
X 
 
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 or MUGA scan for LVEF  only done as clinically indicated. The same procedure used at 
screening should be used throughout the study. 
12. To be done every 3 weeks until suspected PD   
13. IgD/IgE testing is only required for participants with IgD or IgE myeloma.  
14. At the time of suspected disease progression or as clinically indicated. Same modality used at 
Screening should be used throughout study.  
15. 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. 
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 participants 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. Please refer to Table 6 for scheduled BM collection procedures to include aspirate and biopsy. 
18. Assessed in CE Phase only 
19. Participants with ocular signs at the end of study treatment visit will have follow-up questionnaires 
every 3 months (±7 days) until resolution of ocular signs or up to 1 year post treatment 
discontinuation, whichever is soonest.  
20. Must be conducted via telephone within approximately 21 days of the end of study visit. 
21. Optional interview to be conducted via telephone approximately 6 months after EOT. 
Skeletal Survey14,15 
X 
X 
 
Imaging for 
Extramedullary 
Plasmacytoma 
Assessment (by whole 
body CT or whole body 
MRI or CT/PET 
X14,16 
X14,16 
 
Bone Marrow (BM) Aspiration/Biopsy 
BM aspirate and/or core 
biopsy for Disease 
assessment 
X17 
X17 
 
BM core biopsy to 
assess sCR 
X17 
X17 
 
Health Outcomes18 
PRO-CTCAE 
X 
 
 
OSDI 
X19 
X19 
X19 
EORTC-QLQ-C30 and 
EORTC-IL52 
X 
 
 
Qualitative interview 
X20 
X21 
X21 
Schedule Survival 
Status phone call 
X3 
 
X3 
AE = Adverse Event; BP = Blood pressure; BCVA = Best corrected visual acuity; BNP = B-type natriuretic peptide; CR = Complete response; CRP = C-reactive protein; 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; MDRD = Modified Diet in Renal Disease; MP = Master Protocol; MRD = 
Minimal residual disease; MRI = Magnetic resonance imaging; MUGA = multiple gated acquisition; NEI-VFQ-25 = National Eye Institute 25-item Visual Function Questionnaire; OS = 
Overall survival; OSDI = Ocular Surface Disease Index; PBMC Peripheral Blood 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; QID = 4 times a day; SAE = 


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Serious Adverse Event; 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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Table 6 
Bone Marrow Aspiration/Biopsy Collection 
Timepoint 
BM aspirate for 
FISH testinga,b, 
c,d 
BM (core biopsy and/or aspirate) for disease 
assessmenta,c,d 
Screening 
X 
X 
Suspected 
CR/sCR 
X 
X 
PD (only if PD 
not evident 
otherwise) 
 
X 
BCMA = B-cell maturation antigen; BM = bone marrow; EoT = end of treatment; FISH = 
fluorescence in situ hybridization; MRD = minimal residual disease; PFS = progression-free 
survival; Q3W = every 3 weeks; sCR = stringent complete response.  
Note: Bone marrow assessment will be done approximately every 3 - 4 treatment cycles (~ 
every 9 - 12 weeks), in alignment with IMWG criteria/clinical practice guidelines for MM 
(208887 MP Section 8.1), and as needed based upon disease status/treatment response 
(ie, VGPR, CR) as outlined below. 
a. 
These assessments will be performed at a local laboratory. For FISH testing, if testing 
cannot be performed at a local lab the samples can be sent to the central lab. 
b. 
Screening- 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. 
c. 
At Screening, immunohistochemistry (IHC) of bone marrow core biopsy is preferred for 
quantitative assessment of malignant plasma cells (PC).  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. 
For participants who discontinue IP for reasons other than PD and have current disease 
response of PR or better, Notes f and g below are applicable: 
d. 
At EoT or /PFS, only to confirm CR/sCR or suspected PD at this visit for plasma cell 
assessment by IHC or aspiration. For stringent CR in participants achieving a CR, bone 
marrow core biopsy is required to confirm sCR by IHC for absence of clonal cells.  Only 1 
marrow procedure required for CR and sCR assessment. 
 
 
  
 
 


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Table 7 
SoA – Additional Procedures for Participants HBcAb Positive 
The procedures listed in this table apply ONLY to participants in screening or who have been 
enrolled and who have positive HBcAb; all procedures must be done in addition to the required 
procedures for all participants detailed in Table 2 to Table 6 
HBV Study 
Assessments 
During 
Screening / 
Prior to 
starting 
treatment 
During 
Treatment EOT 
Notes 
HBV-DNA testing 
X 
X 
X 
HBV-DNA testing prior to the 
start of belantamab mafodotin 
and subsequently every 3 
months, or if liver function test 
elevations requiring increased 
monitoring or stopping criteria 
occur, or for any clinical 
suspicion of Hepatitis 
reactivation. 
 
 
 


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2. 
INTRODUCTION 
2.1. 
Rationale for Combination of Belantamab mafodotin with 
Dostarlimab 
Belantamab mafodotin causes auristatin-induced immunogenic cell death (ICD) on target 
MM tumor cells [Montes De Oca, 2019; Montes De Oca, 2021] and therefore, 
belantamab mafodotin is a good candidate for combining with immune checkpoint 
inhibitors.  ICD is characterized by induction of the endoplasmic reticulum (ER) stress 
response and exposure of danger-associated molecular patterns (DAMPs), many of which 
are Toll-like receptor ligands.  Exposure of dendritic cells to tumor cells undergoing ICD 
evokes an inflammatory phenotype (innate response) including an increase in co-
stimulatory markers CD86 and MHC Class II antigens, and activation of NFB, an 
intermediate of inflammatory signaling pathways.  Mature dendritic cells (DCs) play key 
roles in priming robust immune responses in tumor-bearing hosts and ICD can induce an 
effective anti-tumor immune response through activation of DCs and consequent 
activation of specific T cell responses, by priming tumor antigen-specific T cells 
[Kroemer, 2013; Muller, 2014].  The T cell anti-tumor response can be further augmented 
by a PD-1 inhibitor, such as dostarlimab.  Programmed cell death-1 (PD-1) expressed on 
T cells is a member of the CD28 superfamily that delivers negative signals upon 
interaction with its two ligands, programmed cell death ligand 1 (PD-L1) or programmed 
cell death ligand 2 (PD-L2). Physiologically, PD-1 and its ligands are broadly expressed 
and exert a wider range of immunoregulatory roles in T cell activation and tolerance.  
Recent studies show that PD-1/PD-L1 interaction regulates the induction and 
maintenance of peripheral tolerance and protects tissues from autoimmune attack. PD-1 
and its ligands are also involved in attenuating tumor immunity and facilitating tumor 
progression.  
Many tumors, including MM, use various escape mechanisms to evade immune control 
and promote tumor growth [McLaughlin, 2016].  One of those mechanisms is the 
expression of PD-1 ligands (PD-L1).  Recent advances in cancer treatment include 
successful checkpoint blockade by using antibodies binding to PD-1 or PD-L1 (e.g., 
pembrolizumab, nivolumab).  The anti-PD-1 and anti-PD-L1 antibodies have a favorable 
safety profile and have resulted in durable responses in a variety of cancers, including 
melanoma, kidney cancer, lung cancer, and Hodgkin lymphoma.  The agents continue to 
be evaluated in various solid tumors and hematological malignancies, alone or in 
combination with other therapies [Dolan, 2014].  There is also a growing body of data 
demonstrating broad expression of PD-1 and its ligands in the microenvironment of MM, 
indicating an important role of the PD-1 pathway [Liu, 2011; Kuranda, 2010; 
Atanackovic, 2014; Benson, 2010].  Although thus far, anti-PD-1 treatment alone has not 
been effective in MM [Lesokhin, 2014; Suen, 2015], there is a recent report of a sCR 
(ongoing for 27 months at time of publication) achieved in a patient with high-risk 
smoldering MM following pembrolizumab monotherapy [Manasanch, 2019].  The 
KEYNOTE-023 study examined whether an anti-PD-1 treatment (Keytruda 
[pembrolizumab]) in combination with immunomodulatory agents, may create 
synergism, in this case with lenalidomide and dexamethasone.  Lenalidomide doses of 10 
mg and 25 mg were examined, with the 25 mg dose further explored.  Of the participants 
evaluable for efficacy (N=40), 88% of participants had a decrease in M protein.  The 


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ORR for this population was 50%, including a 38% ORR for participants who were 
lenalidomide refractory [Mateos, 2016].  Based on these findings, the KEYNOTE-183 
and KEYNOTE-185 Phase 3 studies were initiated, exploring combinations of 
pembrolizumab with IMiDs. 
Following review of both studies by data monitoring committees, KEYNOTE-183 and 
KEYNOTE-185 were placed on full clinical hold.  In both studies, it was determined that 
the benefit-risk was unfavorable for the combination of pembrolizumab with IMiDs.  The 
US FDA also placed Cohort 1 (combination with lenalidomide and dexamethasone) of 
KEYNOTE-023 on full clinical hold as a result of the data from KEYNOTE-183 and 
KEYNOTE-185.  
Keynote-183 was a randomized trial which evaluated pomalidomide and low-dose 
dexamethasone with or without pembrolizumab in participants with relapsed and 
refractory multiple myeloma.  The ORR was 34% in the pembrolizumab containing arm 
versus 40% in the control arm without pembrolizumab; however, there was no difference 
in time-to-progression between arms.  There were 29 deaths in the pembrolizumab arm 
compared to 21 in the control arm, reflecting an overall survival hazard ratio of 1.61 
(95% CI: 0.91, 2.85) [Krauss, 2018].  An analysis conducted with the removal of 
participants with high-risk disease characteristics (high-risk cytogenetics, plasmacytoma 
and quadruple refractory status) resulted in a similar number of deaths (n=13) in both 
arms [Mateos, 2018], suggesting perhaps an imbalance of patients with high risk disease 
between treatment arms.  
Keynote-185 was a randomized trial which evaluated lenalidomide and dexamethasone 
with or without pembrolizumab in participants with newly diagnosed multiple myeloma.  
The ORR was 64% in the pembrolizumab containing arm versus 62% in the control arm 
without pembrolizumab; however, there was no difference in time-to-progression 
between arms.  There were 19 deaths in the pembrolizumab arm compared to 9 in the 
control arm, reflecting an overall survival hazard ratio of 2.06 (95% CI: 0.93, 4.55) 
[Krauss, 2018].  
There were no unifying causes of death or unique adverse event patterns in both studies 
that could explain the observed effects on overall survival [Gormley, 2018]. 
Enrollment was also halted (due to pembrolizumab findings cited above) on Checkmate 
602, a randomized Phase 3 trial comparing the PD-1 inhibitor nivolumab plus 
pomalidomide–dexamethasone with pomalidomide–dexamethasone alone in patients with 
RRMM.  The trial was re-opened for enrollment in May 2018 while a concurrent early 
futility analysis was performed at FDA request based on 170 of participants enrolled. 
Enrollment was subsequently stopped in September 2018 based on the results of this 
analysis, with a median f/u of 9.3 months and HR for PFS of 1.08 (95% CI: 0.68-1.70) 
and OS of 1.19 (95% CI: 0.64-2.2) were observed with nivolumab-Pd (NPd) when 
compared to Pd alone [Gormley, 2018; Lesokhin, 2019].  
Researchers could again not find any unifying cause or distinct adverse events associated 
with the excess deaths, nor whether they are attributable solely to the PD-1 drug or to a 
drug interaction [Gormley, 2018]. 


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The safety profiles for monotherapy of pembrolizumab and nivolumab in RRMM are 
consistent with its safety profile in other cancers.  Nevertheless, the above mentioned 
findings along with results of other studies in this patient population suggest that the 
future of PD‐1 inhibition, in combination with other agents as treatment for RRMM, 
should be carefully designed.  Importantly, combinations other than those with 
immunomodulatory agents should be considered [Ribraq, 2019]. 
More recently, the Nivo-Dara study investigated efficacy and safety of nivolumab 
combined with daratumumab (ND), with or without low-dose cyclophosphamide (50 mg 
once daily) (NDc) in RRMM.  Inclusion criteria included ≥2 prior therapies, 
lenalidomide-refractory disease, and prior treatment with a PI-containing regimen.  With 
a median follow-up of 8.6 months, ORR (50%) and deaths due to progressive disease 
(25%) were similar in the treatment arms.  As expected, the infection rate and the need 
for supportive care were higher in patients treated with NDc, the ND regimen was 
selected for further evaluation in the planned part B of the study [Verkleij, 2019]. 
In addition, currently ongoing studies in relapsed MM reflect use of combination 
strategies. Included among these active/recruiting trials are: 
• 
A Study of Atezolizumab (Anti-Programmed Death-Ligand 1 [PD-L1] Antibody) 
Alone or in Combination with an Immunomodulatory Drug and/or Daratumumab in 
Participants with Multiple Myeloma (MM); Phase 1b, NCT02431208; Recruitment 
status: Active, not recruiting; First Posted April 30, 2015; Study start date July 22, 
2015; Last Update Posted February 6, 2020 
• 
NY-ESO-1c259T Alone and in Combination with Pembrolizumab for Multiple 
Myeloma; Phase 2, NCT03168438; Recruitment Status :Recruiting; First Posted 
May 30, 2017; Study start date August 18, 2017; Last Update Posted : October 29, 
2019 
• 
Isatuximab in Combination with Cemiplimab in Relapsed/Refractory Multiple 
Myeloma (RRMM) Patients; Phase 1,2, NCT03194867; Recruitment Status: Active, 
not recruiting; First Posted: June 21, 2017; Study start date February 21, 2018; Last 
Update Posted: January 13, 2020 [ClinicalTrials, 2020] 
Based on the scientific rationale of checkpoint blockade combination with agents such as 
belantamab mafodotin, which leads to ICD, the GSK205207 combination clinical trial of 
belantamab mafodotin and pembrolizumab in patients with RRMM initiated enrollment 
and there have been no safety concerns towards pembrolizumab in 12 treated patients. 
This Sub-study will evaluate the safety and anti-myeloma activity of belantamab 
mafodotin in combination with GSK’s PD-1 inhibitor dostarlimab.  Evidence to date does 
not indicate that overlapping toxicities would be expected between belantamab mafodotin 
and dostarlimab. 
Safety will be closely monitored with dose modification guidelines in Section 6.6, and 
GSK will also use an internal Safety Review Team (iSRT) as described in Section 1.1 of 
the 208887 Master Protocol (MP).  We hypothesize that given the immunogenic 
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tumor activity will be observed in MM participants when treated with the combination of 
belantamab mafodotin and dostarlimab. 
2.2. 
Background for Dostarlimab  
An overview of dostarlimab (GSK4057190; TSR-042) is provided below, a summary of 
all relevant data and information available as of 21 JAN 2020.  Detailed information 
concerning the biology, pharmacology, PK, and safety characteristics can be found in the 
Investigator’s Brochure (IB) for dostarlimab [Dostarlimab, 2021]. 
The broad spectrum of cancers amenable to PD-1 blockade supports the value of 
developing an antibody that targets PD-1 to utilize as a single agent and in combination 
with other therapeutic approaches.  Dostarlimab (also known as TSR-042) is an IgG4 
humanized monoclonal antibody that binds with high affinity to PD-1 resulting in 
inhibition of binding to PD-L1 and PD-L2.  This antibody was generated based on a 
proprietary platform that utilizes affinity maturation to select antibodies with desired 
functional characteristics.  The functional antagonist activity of dostarlimab was 
confirmed in a mixed lymphocyte reaction (MLR) assay demonstrating enhanced 
interleukin-2 production upon addition of dostarlimab. 
Dostarlimab has demonstrated an acceptable clinical and nonclinical safety profile based 
on human experience in participants with advanced or recurrent solid tumors and the 
nonclinical pharmacology and toxicology information.  As of the data cutoff date, key 
toxicities in the observed safety profile are consistent with the safety experience of other 
approved mAb PD-1 inhibitors.  Based on the observed anti-tumor activity of other 
antibodies in the same class, dostarlimab is expected to exhibit clinical activity in a broad 
spectrum of cancers. 
2.2.1. 
Clinical Experience  
As of the clinical cutoff date of 21 January 2020, there were 4 ongoing Phase 1 studies 
and 3 ongoing Phase 2 studies with dostarlimab.  The summary of safety and efficacy 
data provided below is for dostarlimab monotherapy study 4040-01-001, as remaining 
ongoing trials are evaluations of combination therapies.  
In addition, 2 double-blind Phase 3 studies with dostarlimab combination therapy are 
ongoing and, therefore, are not included in the evaluated safety population.  
Dostarlimab Monotherapy Study 4010-01-001 
Study 4010-01-001 is an ongoing, first-in-human Phase 1 study of dostarlimab to 
evaluate the safety and tolerability, PK, pharmacodynamics, and clinical activity of 
dostarlimab in participants with recurrent or advanced solid tumors.  
A total of 21 participants were dosed in the dose escalation phase of the study (Part 1).  
Dose escalation continued to a maximally administered dose of 10 mg/kg every 2 weeks 
(Q2W) and a maximum tolerated dose was not identified.  No dose limiting toxicities 
(DLTs) were observed.  The PK of dostarlimab were dose proportional across the dose 
range tested.  Receptor occupancy was measured by direct binding of dostarlimab to PD-


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1 on T cells from participants in Part 1 and by the dostarlimab induced inhibition of IL-2 
production after ex vivo stimulation of T cells from participants in Part 1.  Maximal 
receptor occupancy was achieved at all doses tested (1, 3, and 10 mg/kg) down to 
dostarlimab plasma concentrations as low as 2.435 μg/mL and was maintained for 
approximately 29 days.  
The pharmacokinetic/pharmacodynamic (PK/PD) data was used to determine the fixed 
dosing tested in Part 2A of the study. In this phase of the study, the safety and tolerability 
of dostarlimab were evaluated at 2 fixed dosing schedules: 500 mg every 3 weeks (Q3W) 
and 1,000 mg every 6 weeks (Q6W).  The recommended therapeutic dose (RTD) regimen 
was determined to be 500 mg Q3W for 4 cycles followed by 1,000 mg Q6W for all 
cycles thereafter.  
The RTD selection was based on a combination of results from a preliminary 2-
compartment population PK model, receptor occupancy data from peripheral blood cells 
of participants in Part 1, and safety data from Part 2A, wherein the 500 mg Q3W and 
1,000 mg Q6W regimens were found to have acceptable tolerability with no observed 
DLTs.  In Part 2A, the PK and pharmacodynamic data confirmed that both dosing 
regimens provided sufficient and sustained drug concentrations to allow for maximal 
receptor occupancy throughout the dosing cycle.  
The RTD is being evaluated in expansion cohorts for mismatch repair-deficient 
(dMMR)/microsatellite instability high (MSI H) and MMR proficient/microsatellite 
stable (MSS) endometrial cancer, non small cell lung cancer (NSCLC), and dMMR/MSI 
H and/or polymerase ε-mutated non endometrial cancer in Part 2B of study.  The PK/PD 
profile of participants in Part 2B of the study was similar to that of participants in Part 2A 
of the study. 
Overall, the safety and tolerability of dostarlimab has been evaluated in 535 participants 
with advanced or recurrent solid tumors who received at least one dose of dostarlimab 
monotherapy (500 mg Q3W for 4 doses followed by 1,000 mg Q6W thereafter) prior to 
the data cut-off date (January 21, 2020) in study 4010-01-001 (GARNET), the first-in-
human Phase 1 study. 
As of 10 August 2018, an irORR of 9.52% (2 of 21 participants) was observed with 
dostarlimab monotherapy in Part 1 of Study 4010-01-001.  Based on Investigator’s 
assessment using irRECIST, both participants achieved a partial response. No participant 
in Part 2A achieved a partial or complete response with dostarlimab monotherapy. 
As of 08 July 2019, efficacy results for Part 2B of the study are available for the 
following 2 cohorts: Cohort A1 (dMMR/MSI-H endometrial cancer) and Cohort F 
(dMMR/MSI-H and/or polymerase ε-mutated non-endometrial cancer).  Based on 
blinded independent central review assessments using RECIST v1.1, ORRs of 43.1% and 
44.0% were observed for the 2 cohorts respectively. 
Given this encouraging clinical activity in heavily pretreated patients with diverse tumor 
types, and the manageable safety profile of dostarlimab, the benefit-risk profile for use of 
dostarlimab for treatment of patients with advanced cancers appears positive. 


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2.2.2. 
Pharmacokinetic Summary  
The PK of dostarlimab is being evaluated in Study 4010-01-001. In Parts 1 and 2A of the 
study, 34 participants were dosed with dostarlimab and included in the PK analysis. Part 
1 included 6 participants dosed with 1 mg/kg, 3 participants dosed with 3 mg/kg, and 
12 participants dosed with 10 mg/kg of dostarlimab.  In Part 2A, 6 participants received 
dostarlimab 500 mg Q3W and 7 participants received dostarlimab 1,000 mg Q6W. In 
Part 2B, 443 participants received the RTD and had PK data available for the analysis as 
of the data cutoff date of 08 July 2019: 267 participants diagnosed with endometrial 
cancer, 67 participants diagnosed with NSCLC, and 109 participants diagnosed with 
dMMR/MSI-H and/or polymerase ε-mutated non-endometrial cancer.  Based on 
noncompartmental data, dostarlimab exhibited dose proportional PK over the dose range 
and dose regimens tested.  Dostarlimab was cleared slowly with a terminal elimination 
half-life ranging from approximately10 to 20 days.  Body weight (range 45.6 to 145.6 kg) 
was not a significant covariant for dostarlimab clearance.  Dostarlimab PK continues to 
be evaluated in Part 2B of Study 4010 01 001 through sparse sampling for all participants 
upon administration of first, fourth, fifth, eighth, and twelfth doses at predose and 0.5 and 
1.5 hours postdose.  For the first 4 doses, participants received dostarlimab at 500 mg 
with a 21-day cycle (Q3W).  Starting at dose 5, participants received dostarlimab at 1,000 
mg with a 42-day cycle (Q6W).  Following 4 cycles of dostarlimab 500 mg Q3W, steady 
state was reached, with comparable trough concentrations at the end of Cycles 3 and 4.  
An increase in dose from 500 mg Q3W to 1,000 mg Q6W resulted in an approximately 
1.7-fold increase in postdose concentrations (Cmax of Cycle 4 compared to Cycle 5).  
Similar mean trough concentrations were observed for 500 mg Q3W (mean predose 
Cycles 4 and 5: 72.85 and 82.86 µg/mL, respectively) and 1,000 mg Q6W (mean predose 
Cycles 8 and 12: 85.29 and 77.68 µg/mL, respectively).  When dosed at the RTD 
regimen, dostarlimab showed an approximate 2-fold accumulation (Cycle 4 through 
Cycle 12 based on Cmin compared to single-dose data), consistent with the terminal-
phase elimination half-life.  
A population PK model was developed using concentration-time data from 
477 participants who had at least 2 postdose evaluable concentrations, with a total of 
4,308 evaluable observations.  The model was used to simulate concentrations to evaluate 
dostarlimab Cmax, Cavg, and Cmin after 500 mg Q3W and 1,000 mg Q6W following a 
single dose and at steady state.  
A 2-compartment model with nonlinear, time-dependent elimination, and weight as an 
allometric factor on CL and central volume of distribution fit the data well.  Generally, 
the estimated model parameters were comparable to published data of anti PD-1 mAb 
[Ahamadi, 2017; Liu, 2017] with mean steady-state clearance (CLss) of 0.00742 L/hr, a 
Vss of 5.34 L, and a terminal half-life of 25.4 days.  The population clearance estimate 
was approximately 15.5% lower at steady state when compared to single dose due to 
time-dependent changes in this parameter.  Based on model simulations of exposure 
parameters following either 500 mg Q3W or 1,000 mg Q6W dosing, both Cmin and Cavg 
were similar for the 2 dose regimens.  In particular, the comparability of dostarlimab 
steady-state Cavg suggests a similar overall dostarlimab exposure following either the 
500 mg Q3W or 1,000 mg Q6W dosing regimen. 


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2.2.2.1. 
Pharmacodynamics  
Dostarlimab administration resulted in maximal PD-1 occupancy on T cells in peripheral 
blood of participants at all dostarlimab dose levels tested, including with the RTD 
regimen.  Maximal receptor occupancy, as measured by direct PD-1 binding and 
alleviation of inhibition of IL 2 production, was maintained throughout the dosing period 
for all doses and dose regimens tested [Dostarlimab, 2021].  
2.2.2.2. 
Fixed dose selection for dostarlimab monotherapy 
The RTD (500 mg Q3W for 4 cycles, followed by 1,000 mg Q6W for all subsequent 
cycles) selection was based on a combination of results from a preliminary 2-
compartment population PK model, receptor occupancy data from peripheral blood cells 
of participants  in Part 1, and safety data from Part 2A, wherein the 500 mg Q3W and 
1,000 mg Q6W regimens were found to have acceptable tolerability with no observed 
DLTs.  In Part 2A, the PK and pharmacodynamic data confirmed that both dosing 
regimens provided sufficient and sustained drug concentrations to allow for maximal 
receptor occupancy throughout the dosing cycle [Dostarlimab, 2021]. 
2.2.3. 
Safety  
As of 21 January 2020, 535 participants with heavily pretreated advanced solid tumors 
have been treated with dostarlimab monotherapy in Study 4010-01-001: 21 participants 
in Part 1 and 514 participants in Parts 2A and 2B.  As of the data cutoff date, 527 
participants (98.5%) reported at least 1 treatment-emergent adverse event (TEAE), with 
events of fatigue (25.6%), nausea (24.9%), anaemia (23.6%), and diarrhoea (21.5%) 
being the most frequently reported (>20%).  TEAEs that were ≥Grade 3 were reported in 
256 participants (47.9%), and were considered as study drug-related in 70 participants 
(13.1%).  The majority of the ≥Grade 3 events TEAEs occurred in 2% of participants or 
less each, with the exception of anaemia (8.6%), dyspnoea (3.7%), abdominal pain 
(3.4%), fatigue (2.8%), hyponatraemia (2.8%), and pulmonary embolism (2.4%).  Serious 
adverse events (SAEs) occurred in 205 participants (38.3%); 39 participants (7.3%) had 
SAEs considered study drug-related.  Forty-eight participants (9.0%) had a TEAE leading 
to study drug discontinuation.  Twenty-five participants (4.7%) had a TEAE leading to 
study drug discontinuation that was considered study drug-related.  Sixteen participants 
(3.0%) developed a TEAE not related to study drug that led to death.  No study drug 
related TEAE leading to death was reported. 
The safety profile of monotherapy dostarlimab in participants with advanced or recurrent 
solid tumors was generally similar to the reported safety profiles of other mAbs blocking 
the PD-1 interactions [KEYTRUDA PI, 2019; OPDIVO PI, 2019; LIBTAYO PI, 2019]. 
Please see the dostarlimab IB v5 [Dostarlimab, 2021] for additional details. 
2.2.3.1. 
Potential for Drug-Drug Interactions (DDIs) between Belantamab 
Mafodotin and Dostarlimab 
Elimination pathways for belantamab mafodotin and cys-mcMMAF have not been 
characterized in humans.  Cys-mcMMAF was not an inhibitor, an inducer, or a good 


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substrate of cytochrome P450 enzymes in vitro.  In addition, cys-mcMMAF was shown 
to be a substrate of P-glycoprotein (P-gp).  It is unlikely that belantamab mafodotin or 
cys-mcMMAF would impact the PK of dostarlimab. 
No DDI studies have been conducted for dostarlimab. Monoclonal antibodies (mAbs) 
such as dostarlimab are not substrates for cytochrome P450 or drug transporters.  
Dostarlimab is not a cytokine and it is unlikely to be a cytokine modulator.  Additionally, 
PK DDI of dostarlimab with small molecule drugs are not expected [Silva, 2015; Wang, 
2014; ICH, 2011; Varga, 2015].  There is no evidence of DDI mediated by non-specific 
CL of lysosome degradation for antibodies [Silva, 2015]. 
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and 
reasonably expected adverse events of belantamab mafodotin may be found in the IB 
[GSK Document Number RPS-CLIN-004867, GSK2857916 Investigator’s Brochure 
V09, 2021]. 
Belantamab mafodotin risk assessment and mitigation strategies are in the 208887 MP 
Section 2.3.1.  
More detailed information about the known and expected benefits and risks and 
reasonably expected adverse events of dostarlimab may be found in the IB [Dostarlimab, 
2021]. 
2.3.1. 
Risk Assessment  
Table 8 outlines the risk assessment and mitigation strategy for dostarlimab.  Belantamab 
mafodotin risk assessment and mitigation strategies are in the master protocol (MP; see 
Section 2.3.1).  
Table 8 
Potential Risks Related to Dostarlimab 
Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
Risk related to dostarlimab 
Infusion-related reactions 
(IRRs)  
Risk for IRRs and 
hypersensitivity is inherent to 
many mAbs [Brennan, 2010]. 
 
Infusion-related reactions, which 
may be severe, have been 
reported in association with 
dostarlimab.  
Participants will be closely 
monitored for signs of IRR. 
Premedication prior to first 
infusion of belantamab mafodotin 
is not mandatory but may be 
considered based on investigator 
judgement.  
 
If an IRR occurs during 
belantamab mafodotin 
administration, management 
may follow guidance in the 


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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
208887 MP Section 11 or local 
standard of care.  
 
For severe (Grade 3) or life-
threatening (Grade 4) infusion-
related reactions associated with 
dostarlimab, stop infusion and 
permanently discontinue.   
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.  
 
Immune-related AEs have been 
reported in association with 
dostarlimab. 
Participants with the following 
medical history are ineligible for 
this study: 
o Active autoimmune 
disease  
o Severe hypersensitivity 
to another mAb 
 
Established management 
algorithms for irAEs: Refer to the 
208887 MP Section 11 for further 
details on the identification, 
evaluation, and management of 
toxicities including cumulative 
effects, with a potential immune 
etiology. 
Embryo-Fetal Toxicity 
There are no available data on 
the use of dostarlimab in 
pregnant women.  Animal 
reproduction studies have not 
been conducted with dostarlimab 
to evaluate its effect on 
reproduction and fetal 
development.  Based on its 
mechanism of action, 
dostarlimab can cause fetal harm 
when administered to a pregnant 
woman.  Animal models link the 
PD-1/PD-L1 signaling pathway 
with maintenance of pregnancy 
Pregnancy testing outlined in the 
SoA. 
Contraception requirements are 
detailed in the 208887 MP 
Section 12.7.2 


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Potential Risk of Clinical 
Significance 
Summary of Data/Rationale for 
Risk 
Mitigation Strategy 
through induction of maternal 
immune tolerance to fetal tissue. 
2.3.2. 
Benefit Assessment 
Although there is limited human experience with belantamab mafodotin, and no clinical 
experience with the combination of belantamab mafodotin with dostarlimab, given the 
currently available safety data and the low likelihood of drug-drug interactions between 
belantamab mafodotin and dostarlimab, combination therapy may have an acceptable 
safety profile.  Additionally, the combination may provide anti-tumor effect in 
participants with MM. 
The safety profile of dostarlimab is similar to the safety profiles of anti-PD1 drugs 
[Dostarlimab, 2021]. 
2.3.3. 
Overall Benefit: Risk Conclusion 
This is the first study testing the combination of dostarlimab plus belantamab in 
participants with relapsed/refractory multiple myeloma that have been treated with 
standard therapies.  Study participants may benefit from medical tests and screening 
performed during the study.  Any potential benefit of the addition of dostarlimab to 
belantamab mafodotin is unknown.  Data obtained in this study may help identify 
individuals more likely to benefit or have side-effects from dostarlimab plus belantamab 
mafodotin. 
Based on current data from the dostarlimab development program and the observed anti-
tumor activity of other antibodies in the same class, dostarlimab is expected to exhibit 
clinical activity in a broad spectrum of cancers.  
The current nonclinical and clinical safety information for both belantamab mafodotin 
and dostarlimab, used as single agents, provide support for their use in combination in the 
target patient population. Based on the mechanism of action of belantamab mafodotin 
following engagement with both target and the FcRIIIA, leading to ADCC and the 
potential for cytokine release as a result of inflammation secondary to non-specific 
cytotoxicity. Dostarlimab is unlikely to independently induce cytokine release, as 
incubation of dostarlimab with donor PBMCs in vitro did not induce significant 
stimulation of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-2, IL-4, IL-6, and 
IL-10. Dostarlimab is not expected to induce antibody-dependent cell-mediated 
cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC). The potential risk 
for cytokine release when these agents are administered in combination is considered to 
be low. To ensure the safety of participants, a careful dose escalation of belantamab 
mafodotin will be implemented where no more than one participant will be dosed per 
day.  
In addition, the starting dose of belantamab mafodotin in this combination regimen has 
been selected to be 2 dose levels below a dose that has been shown to be well tolerated 


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during the belantamab mafodotin monotherapy dose escalation and should provide a 
sufficient safety margin when dostarlimab is added with starting dose of 500 mg. In 
addition, close clinical monitoring will be implemented. 
Considering the measures taken to minimize risks to participants in the Phase I clinical 
trial, the potential risks identified in association with dostarlimab as a monotherapy or 
combination therapy are justified by the anticipated benefits that may be afforded to 
participants with relapsed/refractory multiple myeloma. 
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 4 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 dostarlimab being described in this Sub-study. 
The starting dose of belantamab mafodotin will be 1.9 mg/kg to be evaluated in Dose 
Level 1, with the highest dose of belantamab mafodotin of 2.5 mg/kg planned for Dose 
Level 2.  
The dose of dostarlimab will be identical across the dose level groups and will be 500 mg 
Q3W for 4 cycles followed by 1000 mg Q6W for subsequent cycles. 
Please see 208887 MP Section 4.1.1 for details of decision making during the DE phase. 
4.2. 
Scientific Rationale for Study Design 
Please refer to the 208887 MP. 
4.3. 
Justification for Dose 
There is no clinical experience with dostarlimab in patients with multiple myeloma. 
The RTD regimen of dostarlimab is 500 mg Q3W for 4 cycles followed by 1000 mg 
Q6W in patients with solid tumor.  This regimen was determined from the results of the 
Phase 1/2 study 4010-01-001, where the PK, efficacy and safety were evaluated over 3 
parts:  
• 
Part 1 (dose escalation): Q2W at doses of 1, 3 and 10 mg/kg  


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• 
Part 2A (Fixed-dose Safety Run-in): 1000 mg Q6W and 500◦mg Q3W  
• 
Part 2B (expansion): 500 mg Q3W for the first 4 cycles followed by 1000 mg Q6W 
The combination of meaningful efficacy responses in mismatch repair deficient 
endometrial cancer patients and overall manageable safety profile of dostarlimab supports 
this therapeutic dose and regimen 
A starting dose of 500 mg Q3W for 4 cycles followed by 1000 mg Q6W is considered an 
appropriate dose for combination therapy with belantamab mafodotin (GSK’916) based 
on the following:  
• 
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 dostarlimab for the dose ranges considered.  
• 
Because the ligands of belantamab mafodotin and dostarlimab are expressed on 
different target cell populations, no DDI related to target mediated disposition is 
expected between belantamab mafodotin and dostarlimab (GSK’190). 
• 
According to currently available data, the flat dose of 500 mg IV Q3W was well 
tolerated and did not result in excessive toxicity in solid tumor patients.  The highest 
tested flat dose was 1000 mg IV Q6W in the Phase 1 4010-01-001 (GARNET) trial; 
this dosing also did not result in excessive toxicity in solid tumor patients.  
4.4. 
Participant Completion and End of Study Definitions 
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: 
Please refer to the 208887 MP. 
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 4 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 4.   
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
The exclusion criteria #36-38 below are in addition to the exclusion criteria already 
defined in 208887 MP Section 5.2.   
36. Patient has an active autoimmune disease that has required systemic treatment in 
the past 2 years (i.e. with use of disease-modifying agents, corticosteroids, or 
immunosuppressive drugs).  
37. Patients who have received prior therapy with an anti-programmed death-1 (anti-
PD-1), anti-PD-1-ligand-1 (anti-PD-L1), or anti-PD-1 ligand-2 (anti-PD-L2) 
agent. 
38. Patient has a diagnosis of immunodeficiency or is receiving systemic steroid 
therapy or any other form of immunosuppressive therapy within 7 days prior to 
the first dose of study treatment. Use of inhaled steroids, local injection of 
steroids, and steroid eye drops are allowed. 
5.3. 
Lifestyle Considerations 
Please refer to the 208887 MP. 
5.4. 
Screen Failures 
Please refer to the 208887 MP. 
6. 
STUDY INTERVENTION 
Study intervention is defined as belantamab mafodotin administered with the sub-study-
specific anti-cancer combination partner treatment and administered to a study participant 
according to the study protocol. 
6.1. 
Study Intervention(s) Administered 
Specifications for belantamab mafodotin and dostarlimab IP in this study are given 
(Table 9). 
Dostarlimab kits will be supplied as a single vial in a carton, open label and non-patient 
specific. IP will be provided in a single-use vial as 50 mg/mL, 10.0 mL volume (500 mg) 
vial.  Expiration date is printed on the product label. The product should be stored 
between 2°C and 8°C, and in accordance with the Pharmacy Manual. 


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Refer to the Pharmacy Manual for additional details on study drug preparation, 
administration, handling, storage, accountability and disposal and/or return of unused 
study treatment(s). 
Table 9 
Belantamab Mafodotin and Dostarlimab Investigational Product 
Intervention Name Belantamab Mafodotin  
Dostarlimab 
Type  
Drug  
Drug 
Dose Formulation 
Lyophilized powder 
50 mg/ml solution 
Unit Dose 
Strength(s) 
100 mg/vial in single-use vial for 
reconstitution 
10 ml (50 mg/ml) single-use vial 
Route of 
Administration 
Delivered as IV solution over  
30-60 minutes (see SRM for 
details) 
Delivered as IV solution over 30 
minutes (see Pharmacy Manual for 
details) 
IP  
Belantamab mafodotin 
Dostarlimab 
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 Dostarlimab 
Belantamab mafodotin and dostarlimab will be administered as per instructions below, 
and participants enrolled in 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. 
 
Belantamab mafodotin 
• 
Belantamab mafodotin will be administered before administration of dostarlimab. 
• 
Belantamab mafodotin will be administered to participants 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 and reported in the 
eCRF. The time of start and end of infusion will be documented in eCRF. 
• 
Belantamab mafodotin will be administered on Day 1 of each cycle at the assigned 
dose as an IV infusion (see Section 6.1 and Section 6.2 for details).  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 the 208887 MP Section 7.1.6 and in 208887 MP Section 11 should be 
followed.  


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• 
After the infusion of belantamab mafodotin has been completed participant will be 
required to enter at least 1 hour rest period before start of dostarlimab infusion. In 
case of IRR during belantamab mafodotin infusion, participant needs to recover to 
Grade 1 or less in order to be able to receive dostarlimab infusion. 
The intended cycle time of belantamab mafodotin is 21 days (+ 3-day window) for Q3W 
administration or 42 days (+3-day window) for Q6W administration and cannot occur 
more frequently than this. 
Dostarlimab  
• 
Participants will receive dostarlimab starting C1D1 and will be treated until disease 
progression, intolerable toxicity, informed consent withdrawal, the end of the sub-
study, study or death. There is no pre-specified duration of therapy after which 
administration must be stopped. 
• 
Dostarlimab will be administered using IV infusion on Day 1 of each treatment cycle 
after all procedures and assessments have been completed.  
• 
Dostarlimab will be administered at flat prescribed dose (outlined below) over 30 
min IV infusion time after at least 1 hour rest period after completion of belantamab 
mafodotin infusion.  Premedication is not required prior to infusion unless deemed 
medically necessary, in which case it should be administered according to 
institutional guidelines/recommendations.  
o 500 mg every 3 weeks for the first 4 doses, followed by  
o 1000 mg every 6 weeks. 
• 
Visit window for treatment of dostarlimab allowed by the protocol is  3 days for 
both Q3W and Q6W schedule. However, it is recommended that sites try to keep 
participants on the original dosing schedule based on C1D1 and maintain the dosing 
intervals as closely as possible to the Q3W and Q6W schedule, respectively. If in the 
judgment of the Investigator, belantamab mafodotin and dostarlimab combination 
treatment needs to be initiated prior to the next planned scheduled dose following a 
dosing delay and where clinical toxicity has resolved, please discuss with the 
Medical Director. 
• 
In case of IRR during or after preceding belantamab mafodotin infusion, the 
administration of dostarlimab will be delayed to allow for recovery to Grade 1 or 
less. In total, the infusion of dostarlimab may be delayed for up to the allowed 
+3-day window from the scheduled dose date to allow for recovery, and to 
accommodate scheduling conflicts in a given cycle. If the participant does not 
recover from IRR to Grade 1 or less within the +3 day window, the dosing of 
dostarlimab will be skipped in a given cycle, and may be resumed in the next cycle. 
• 
All participants are required to remain under observation at the study site for at least 
three hours post-infusion of the last study drug administered for the first two study 
treatment dosing visits. At subsequent study treatment dosing visits, for participants 
who experience infusion-related reactions, the post-infusion observation time should 
remain as at least three hours; for participants who do not experience infusion 
reactions, these participants should remain under observation for a time period not 


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shorter than one hour (or longer as per the judgement of the investigator or as per 
institutional guidelines).  
• 
In case of IRR during dostarlimab administration –please refer to the 208887 MP 
Section 11.1.1 for management guidelines. 
6.3. 
Preparation/Handling/Storage/Accountability 
Please refer to the 208887 MP. 
6.4. 
Measures to Minimize Bias: Randomization and Blinding 
Please refer to the 208887 MP. 
6.5. 
Concomitant Therapy 
Please refer to the 208887 MP. 
6.6. 
Dose Modification 
Dose modification is for belantamab mafodotin when in combination with dostarlimab. 
For information related to overall dose modification refer to the 208887 MP.  Also see 
208887 MP Section 11 for guidelines on dose modification and management of events 
for belantamab mafodotin and other partner combination treatments. 
Table 10 
Permitted Dose Reductions for Belantamab Mafodotin when in 
Combination with Dostarlimab 
Belantamab mafodotin) Starting Dose Level 1st Dose Reduction 
2.5 mg/kg 
1.9 mg/kg 
1.9 mg/kg 
 
• 
If the participant cannot tolerate belantamab mafodotin after the allowed dose 
reductions, he or she must be withdrawn from study treatment for lack of 
tolerability.  
• 
Resuming treatment with belantamab mafodotin may be considered after the toxicity 
has resolved to Grade 1 or less. 
• 
For further details regarding dose modifications see 208887 MP Section 11. 
No dose reductions are allowed for dostarlimab.   
Dose Modification Guidelines for immune related Adverse Events are listed in the 
208887 MP Section 11. For immune related encephalitis event of any Grade, dostarlimab 
should be discontinued. 
If belantamab mafodotin is held or discontinued for any toxicity, dostarlimab is also to be 
held or discontinued. 


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7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT WITHDRAWAL FROM THE STUDY 
Please refer to the 208887 MP. 
7.1. 
Discontinuation of Study Intervention 
Please refer to the 208887 MP. 
7.2. 
Participant Withdrawal from the Study 
Please refer to the 208887 MP. 
7.3. 
Lost to Follow Up 
Please refer to the 208887 MP. 
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 4 are in Section 8.3.7, Section 8.3.10 and 
Section 8.4 below. 
8.1. 
Efficacy Assessments 
Please refer to the 208887 MP. 
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 
Please refer to the 208887 MP. 
8.3.2. 
Method of recording AE and SAE information 
Please refer to the 208887 MP. 
8.3.3. 
Method of Detecting AEs and SAEs 
Please refer to the 208887 MP. 


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8.3.4. 
Follow-up of AEs and SAEs 
Please refer to the 208887 MP. 
8.3.5. 
Reporting of Potentially Life-Threatening AEs to the GSK Medical 
Director 
Please refer to the 208887 MP. 
8.3.6. 
Regulatory Reporting Requirements for SAEs 
Please refer to the 208887 MP. 
8.3.7. 
Management of Pregnancy 
Details of all pregnancies in female participants will be collected after the start of study 
treatment and for 4 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 6 months following last dose of belantamab mafodotin. 
8.3.8. 
Cardiovascular and Death Events 
Please refer to the 208887 MP. 
8.3.9. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs 
Please refer to the 208887 MP. 
8.3.10. 
Adverse Events of Special Interest 
Information on belantamab mafodotin AESI are contained in the 208887 MP 
Section 8.3.10. 
Immune-related TEAEs for dostarlimab are summarized in Section 5.4.6 of Dostarlimab 
IB v5 [Dostarlimab, 2021]. 
8.4. 
Treatment of Overdose 
Guidelines for management of belantamab mafodotin overdose are contained in the 
208887 MP Section 8.4. 
An overdose of dostarlimab is defined as any dose that is ≥ 20% than the intended 
dostarlimab dose.  For fixed doses, an overdose of dostarlimab is defined as any dose that 
is ≥20% than 1000 mg Q6W.  All overdoses, regardless of associated AE/SAE are to be 
reported as described for SAEs and as per the SAE form completion guidelines.  Obtain 
an additional plasma sample for PK analysis if requested by the GSK Medical Director. 


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8.5. 
Pharmacokinetics 
Not applicable. 
8.6. 
Genetics 
Please refer to the 208887 MP. 
8.7. 
Immunogenicity Assesments 
Please refer to the 208887 MP. 
8.8. 
Biomarkers 
Not applicable  
8.9. 
Health-Related Quality of Life 
Please refer to the 208887 MP. 
9. 
STATISTICAL CONSIDERATIONS 
Please refer to the 208887 MP for the overall Statistical Considerations for the study. 
9.1. 
Statistical Hypotheses 
Please refer to the 208887 MP. 
9.2. 
Sample Size Determination 
Please refer to the 208887 MP. 
9.3. 
Populations for Analyses 
Please refer to the 208887 MP. 
9.4. 
Statistical Analyses 
Please refer to the 208887 MP. 
9.5. 
Interim Analysis 
Please refer to the 208887 MP. 
9.6. 
Sample Size Sensitivity 
Please refer to the 208887 MP. 


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10. 
REFERENCES 
Ahamadi M, Freshwater T, Prohn M, et al. Model-Based Characterization of the 
Pharmacokinetics of Pembrolizumab: A Humanized Anti-PD-1 Monoclonal Antibody in 
Advanced Solid Tumors. CPT Pharmacometrics Syst Pharmacol. 2017;6(1):49-57. 
Atanackovic D, Luetkens T, Kroger N. Coinhibitory molecule PD-1 as a potential target 
for the immunotherapy of multiple myeloma. Leukemia. 2014;28:993-1000. 
Benson DM, Bakan CE, Mishra A, Hofmeister CC, Efebera Y,Caligiuri MA. The PD-
1/PD-L1 axis modulates the nature killer cell versus multiple myeloma effect: a 
therapeutic target for CT-001, a novel monoclonal anti-PD-1 antibody. Blood. 
2010;116:2266-2294. 
Blank C, Brown I, Peterson AC, et al. PD-L1/B7H-1 inhibits the effector phase of tumor 
rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res. 
2004;64(3):1140-1145. 
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. 
Bristol-Myers Squibb Company (2019) OPDIVO (nivolumab) Prescribing Information 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125554s070lbl.pdf 
Chen L, Han X. Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J 
Clin Invest. 2015;125(9):3384-3391. 
ClinicalTrials.gov. “PD-1s in Multiple Myeloma” searched March, 2020. 
https://clinicaltrials.gov/ Mar2020. 
D'Addio F, Riella LV, Mfarrej BG, et al. The link between the PDL1 costimulatory 
pathway and Th17 in fetomaternal tolerance. J Immunol. 2011;187(9):4530-4541. 
Dolan DE, Gupta S. PD-1 pathway inhibitor: changes the landscape of cancer 
immunotherapy. Cancer Control. 2014;21:231-7. 
Dostarlimab Investigator’s Brochure v5, TESARO. March, 2021. 
Ghosn M, Kourie HR, Abdayem P, Antoun J, Nasr D. Anal cancer treatment: current 
status and future perspectives. World J Gastroenterol. 2015;21(8):2294-2302. 33.  
Gormley NJ, Pazdur R. Immunotherapy Combinations in Multiple Myeloma- Known 
Unknowns. N Engl J Med. 2018;379(19):1791-1795. 
GSK Document Number RPS-CLIN-004867 , GSK2857916 Investigator’s Brochure 
V09, 2021 


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Hamanishi J, Mandai M, Ikeda T, et al. Safety and Antitumor Activity of Anti-PD-1 
Antibody, Nivolumab, in Patients With Platinum-Resistant Ovarian Cancer. J Clin Oncol. 
2015;33(34):4015-4022. 
International Council on Harmonisation. ICH Guideline S6 Preclinical Safety Evaluation 
Of Biotechnology-Derived Pharmaceuticals. 2011. Available at: 
http://www.ich.org/products/guidelines.html. 
Krauss AC, Mulkey F, Shen YL, Rosenberg A, Miller B, Carioti T, et al. FDA analysis of 
pembrolizumab trials in multiple myeloma: Immune related adverse events (irAEs) and 
response. J Clin Oncol. 36;2018 (suppl; abstr 8008). 
Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. 
Annu. Rev. Immunol. 2013;31:51-72. 
Kuranda K, Berthon C, Dupont C, Wolowiec D, Leleu X,Quesnel B. A subpopulation of 
malignant CD34+CD138+B7-H1+ plasma cells is present in multiple myeloma patients. 
Experimental Hematology. 2010;38:124-131. 
Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A,Timmerman J. 291 
Preliminary Results of a Phase I Study of Nivolumab (BMS-936558) in Patients with 
Relapsed or Refractory Lymphoid Malignancies. 56th ASH Annual Meeting and 
Exposition, San Francisco, CA. 2014;December:6-9. 
Lesokhin AM, Bal S, Badros AZ. Lessons learned from checkpoint blockade targeting 
PD-1 in multiple myeloma. Cancer Immunol Res. 2019;7(8):1224-1229. 
Liu C, Yu J, Li H, et al. Association of time-varying clearance of nivolumab with disease 
dynamics and its implications on exposure response analysis. Clin Pharmacol Ther. 
2017;101(5):657-666. 
Liu F, Lang R, Zhao J, Zhang X, Pringle GA, Fan Y, et al. CD8 (+) cytotoxic T cell and 
FOXP3(+) regulatory T cell infiltration in relation to breast cancer survival and molecular 
subtypes. Breast Cancer Res Treat. 2011;130:645-655. 
Lonial S, Lee HC, Badros A, Trudel S, Nooka AK, et al. Belantamab mafodotin for 
relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-
label, phase 2 study. Lancet Oncol. 2020 Feb;21(2):207-221. 
Manasanch EE, Han G, Mathur R, et al. A pilot study of pembrolizumab in smoldering 
myeloma: report of the clinical, immune, and genomic analysis. Blood Adv. 
2019;3(15):2400-2408. 
Mateos MV, Blacklock H, Schjesvold F, Oriol A, Simpson D, George A, et al. A Phase 3 
Randomized Study of Pembrolizumab Plus Pomalidomide and Dexamethasone for 
Relapsed/Refractory Multiple Myeloma: KEYNOTE-183. J Clin Oncol. 36;2018 (suppl; 
abstr 8021). 
Mateos MV, Orlowski RZ, Siegel DSD, Reece DE, Moreau P, Ocio EM et al. 
Pembrolizumab in combination with lenalidomide and low-dose dexamethasone for 


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relapsed/refractory multiple myeloma: Final efficacy and safety analysis. DOI: 
10.1200/JCO.2016.34.15_suppl.8010 Journal of Clinical Oncology 34, no. 15_suppl 
(May 2016) 8010-8010. 
McLaughlin J, Han G, Schalper KA, Carvajal-Hausdorf D. Pelekanou V, Rehman J, et al. 
Quantitative assessment of the heterogeneity of PD-L1 expression in non-small-cell lung 
cancer. JAMA Oncol. 2016;2:46-54.  
Merck & Co. Inc. (2019), KEYTRUDA (pembrolizumab) Prescribing Information. 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125514Orig1s054lbl.pdf 
Montes De Oca R, Alavi AS, Vitali N, Bhattacharya S, Blackwell C, Patel K, et al. 
Belantamab Mafodotin (GSK2857916) Drives Immunogenic Cell Death and Immune-
Mediated Anti-Tumour Responses In Vivo. Mol Cancer Ther. 2021;molcanther.MCT-21-
0035-A.2021. Doi: 10.1158/1535-7163.MCT-21-0035. 
Montes De Oca R, Bhattacharya S, Vitali N, Patel K, Kaczynski H, et al. The Anti-
BCMA Antibody-drug Conjugate GSK2857916 Drives Immunogenic Cell Death and 
Immune-mediated Anti-tumor Responses, and in Combination with an OX40 Agonist 
Potentiates In Vivo Activity. HemaSphere. 2019;3(S1):231. 
Muller P, Martin K, Theurich S, Schreiner J, Savic S, Zippelius A. Microtubule-
depolymerizing agents used in antibody-drug conjugates induce antitumor immunity by 
stimulation of detrictic cells. Cancer Immunol Res. 2014;2 (8):741-55. 
Regeneron Pharmaceuticals Inc. (2019) LIBTAYO (cemiplimab-rwlc) Prescribing 
Information. 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/761097s001lbl.pdf 
Ribraq V, Avigan DE, Green DJ, Wise-Draper T, Posada JG, et al. Phase 1b trial of 
pembrolizumab monotherapy for relapsed/refractory multiple myeloma: KEYNOTE-013. 
Br J Haematol. 2019;186(3):e41-e44. Available at: doi: 10.1111/bjh.15888. 
Silva JP, Vetterlein O, Jose J, Peters S, Kirby H. The S228P mutation prevents in vivo 
and in vitro IgG4 Fab-arm exchange as demonstrated using a combination of novel 
quantitative immunoassays and physiological matrix preparation. J Biol Chem. 
2015;290(9):5462-5469. 
Suen H, Brown R, Yang S, Ho PJ. Gilson J, Joshua D. The failure of immune checkpoint 
blockage in multiple myeloma with PD-1 inhibitors in a phase 1 study. Leukemia. 2015 
Jul;29(7):1621-2. doi: 10.1038/leu.2015.104. Epub 2015 May 19.  . 
Varga A, Piha-Paul SA, Ott PA, et al. Antitumor activity and safety of pembrolizumab in 
patients (pts) with PD-L1 positive advanced ovarian cancer: interim results from a phase 
Ib study. J Clin Oncol. 2015;33. 
Verkleij CPM, Minnema MC, Weerdt O, et al. Efficacy and Safety of Nivolumab 
Combined with Daratumumab with or without Low-Dose Cyclophosphamide in 
Relapsed/Refractory Multiple Myeloma; Interim Analysis of the Phase 2 Nivo-Dara 
Study Blood. 2019;134(supplement1):1879. 


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Wang C, Thudium KB, Han M, et al. In vitro characterization of the anti-PD-1 antibody 
nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer 
Immunol Res. 2014;2(9):846-856. 
Zhang L, Gajewski TF, Kline J. PD-1/PD-L1 interactions inhibit antitumor immune 
responses in a murine acute myeloid leukemia model. Blood. 2009;114(8):1545-1552. 


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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. 
Additional guidelines specific to Sub-study 4 are provided in Table 11. 
Table 11 
Guidelines for Treatment and Management of Immune-Related 
Adverse Events of Interest- Dostarlimab 
Toxicity  
Grade/description of 
toxicity 
Recommendations 
Immune-related 
Encephalitis   
Any grade  
Permanently discontinue  
 


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12. 
APPENDICES: SUPPORTING DOCUMENTATION AND 
OPERATIONAL CONSIDERATIONS 
12.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
Please refer to the 208887 MP. 


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12.2. 
Appendix 2: Clinical Laboratory Tests 
Please refer to the 208887 MP. 


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12.3. 
Appendix 3: AEs: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
Please refer to the 208887 MP. 


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12.4. 
Appendix 4: ECOG Performance Status 
Please refer to the 208887 MP. 


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12.5. 
Appendix 5: NYHA Functional Classification System 
Please refer to the 208887 MP. 


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12.6. 
Appendix 6: Modified Diet in Renal Disease 
Please refer to the 208887 MP. 


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12.7. 
Appendix 7: Contraceptive Guidance and Collection of 
Pregnancy Information 
Please refer to the 208887 MP. 


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12.8. 
Appendix 8: Genetics 
Please refer to the 208887 MP. 


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12.9. 
Appendix 9: Liver Safety: Required Actions and Follow-up 
Assessments and Study Treatment Rechallenge Guidelines 
Please refer to the 208887 MP. 


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12.10. 
Appendix 10: Eye Care Specialist- Qualifications and 
Requirements 
Please refer to the 208887 MP. 
12.11. 
Appendix 11: Decentralized and Remote Assessment 
Approaches 
Please refer to the 208887 MP. 


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12.12. 
Appendix 12: Abbreviations and Trademarks 
ABC 
Airway breathing and circulation 
ADC 
Antibody drug conjugate 
ADCC 
Antibody dependent cellular cytotoxicity 
AE 
Adverse event 
AESI 
Adverse events of Special Interest 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
APRIL 
A proliferation-inducing ligand 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration-time curve 
AUC (0-∞) 
Area under the concentration-time curve to infinity 
AUC (0-) 
Area under the concentration time curve over the dosing interval 
AV 
Atrioventricular 
BAFF/BlyS 
B-cell activating factor/B-lymphocyte stimulator 
BAL 
Bronchoaveolar lavage 
BCMA 
B cell maturation antigen 
BCRP 
Breast cancer resistant protein 
BCVA 
Best corrected visual acuity 
BED 
Biologically Effective Dose 
BIW 
Twice a week 
BLRM 
Bayesian logistic regression modelling 
BM 
Bone Marrow 
BSA 
Body surface area 
BWT 
Body weight 
CA 
Competent Authority 
Car-T 
Chimeric Antigen T cell therapy  
CBC 
Complete blood count 
CBR 
Clinical benefit rate 
CDISC 
Clinical Data Interchange Standards Consortium 
CE 
Cohort Expansion phase 
CI 
Confidence interval 
CK 
Creatine kinase 
CK-MB 
Creatine kinase MB-isoenzyme 
CL 
Clearance 
CLL 
Chronic lymphocytic leukemia 
Cmax 
Maximum plasma drug concentration 
CMMC 
Circulating multiple myeloma cells 
CNS 
Central nervous system 
CONSORT 
Consolidated Standards of Reporting Trials 
CPMS 
Clinical Pharmacology Modeling and Simulation 
CPR 
Cardio-pulmonary resuscitation 
CR 
Complete response 
CRM 
Continual Reassessment Method 
CRP 
C-reactive protein 


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CRT 
Calreticulin  
CT 
Computer tomography 
CTCAE 
Common Toxicity Criteria for Adverse Events 
cTn 
Cardiac troponin 
Ctrough 
Trough plasma concentration 
CYP 
Cytochrome P450 
CV% 
Coefficient of variation percent  
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 
DMPK 
Drug metabolism and pharmacokinetics 
DNA 
Deoxyribonucleic acid 
EC 
Ethics committee 
EC50 
Concentration associated with 50% maximal effect 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECL 
Electrochemiluminescence 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
eGFR 
Estimated Glomerular Filtration Rate 
EM 
Extramedullary 
EOI 
End of infusion 
EORTC QLQ 
European Organisation for Research and Treatment of Cancer 
Quality of Life Questionnaires 
FACTS 
Fixed and adapted clinical trials simulator 
FISH 
Fluorescence in situ hybridization 
FLC 
Free light chain 
FSH 
Follicle stimulating hormone 
FTIH 
First time in human 
G-CSF 
Granulocyte colony stimulating factor 
GFR 
Glomerular filtration rate 
GI 
Gastrointestinal 
GLDH 
Glutamate dehydrogenase 
GLP 
Good laboratory practice 
GM-CSF 
Granulocyte macrophage colony stimulating factor 
GSI 
Gamma secretase inhibitor 
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 


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HBc 
Hepatitis B core 
HbcAb 
Hepatitis B core antibody 
HBV 
Hepatitis B 
HCV 
Hepatitis C 
HIPAA 
Health Insurance Portability and Accountability Act 
HMGB1 
High mobility group box 1 
HNSTD 
Highest non-severely toxic dose 
HPLC 
High performance liquid chromatography 
HRT 
Hormone replacement therapy 
HSCT 
Hematopoietic stem cell transplant 
IB 
Investigator’s Brochure 
IC50 
Concentration associated with 50% inhibition of maximal effect  
ICD 
Immunogenic cell death 
ICF 
Informed consent form 
ICH 
International Council on Harmonization 
IDSL 
Integrated Data Standards Library 
IEC 
Institutional ethics committee 
Ig 
Immunoglobulin 
IHC 
Immunohistochemistry 
IMIDs 
Immunomodulators 
IMWG 
International Myeloma Working Group 
INR 
International normalized ratio 
IP 
Intraperitoneal 
IRB 
Institutional review board 
IRC 
Independent review committee 
IRR 
Infusion-related reaction 
ITT 
Intent-to-treat 
IUD 
Intrauterine device 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous 
IVRS 
Integrated voice response system 
KIM-1 
Kidney injury molecule-1 
LBCL 
Large B-cell lymphoma 
LDH 
Lactate dehydrogenase 
LFT 
Liver function test 
LLN 
Lower limit of normal 
LVEF 
Left ventricular ejection fraction 
MABEL 
Minimum anticipated biological effect level 
mAb 
Monoclonal antibody 
Mc 
Maleimidocaproyl 
MDRD 
Modified diet in renal disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Myocardial infarction 
MM 
Multiple Myeloma 
mm3 
Millimeter cube 
MMAF 
Monomethyl auristatin F 


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MoA 
Mechanism of action 
MP 
Master Protocol 
MR 
Minimal response 
MRD 
Minimal residual disease 
MRI 
Magnetic resonance Imaging 
MSDS 
Material safety data sheet 
MTD 
Maximum Tolerated Dose 
mTNBC 
Metastatic triple negative breast cancer 
mTPI 
Modified toxicity probability interval 
MUGA 
Multiple gated acquisition 
NAG 
N-Acetyl-β-D-glucosaminase 
NCI-CTCAE 
National Cancer Institute – Common Toxicity Criteria for Adverse 
Events 
N-CRM 
A modification of the Continual Reassessment Method (CRM) 
proposed by Neuenschwander et al. 
NHV 
Normal healthy volunteers 
NICD 
NOTCH intracellular domain 
NF-B 
Nuclear factor kappa light-chain enhancer of activated B cells 
NT-proBNP 
N-terminal B-type natriuretic peptide 
NK 
Natural killer 
NONMEM 
Non linear mixed effects modelling 
NYHA 
New York Heart Association 
OAT 
Organic anion transporter 
OATP 
Organic anion transporter polypeptide 
ORR 
Overall response rate 
OS 
Overall survival 
OSDI 
Ocular Surface Disease Index 
PBMC 
Peripheral blood mononuclear cells 
PCR 
Polymerase chain reaction 
PD 
Progressive disease 
PD-L1 
Programmed death-ligand 1 
PET 
Positron emission tomography 
PFS 
Progression-free survival 
PFT 
Pulmonary function test 
Pgp 
P-glycoprotein 
PI 
Proteasome inhibitor 
PK 
Pharmacokinetic(s) 
PK/PD 
Pharmacokinetic(s)/Pharmacodynamic(s) 
PR 
Partial response 
PRO 
Patient reported outcome 
PT 
Prothrombin time 
PTS 
Platform technologies and sciences 
PTT 
Partial thromboplastin time 
Q3W 
Every 3 week 
QID 
4 times a day 
QoL 
Quality of life 


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RAP 
Reporting and analysis plan 
RAMOS 
Registration and medication ordering system 
REML 
Restricted maximum likelihood 
RIBA 
Recombinant immunoblot assay 
RNA 
Ribonucleic acid 
Ro 
Observed accumulation ratio 
RO 
Receptor occupancy 
RPA-1 
Renal papillary antigen-1 
RP2D 
Recommended Phase 2 dose 
RRMM 
Relapsed/refractory multiple myeloma 
RT-qPCR 
Reverse transcription quantitative polymerase chain reation 
RTD 
Recommended therapeutic dose 
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 reference manual 
SRT 
Safety Review Team 
SPR 
Surface plasmon resonance 
t½  
Half-life 
TALL 
T-cell acute lymphoblastic leukemia 
TBNK 
T-cell, B-cell and Natural Killer cells 
TEAE 
Treatment emergent adverse event 
Tlast 
Time of last quantifiable concentration 
TLS 
Tumor lysis syndrome 
Tmax 
Time to maximum drug concentration 
TNBC 
Triple negative breast cancer 
TTP 
Time to progression 
TTR 
Time to response 
ULN 
Upper limit of normal 
UPEP 
Urine protein electrophoresis 
VGPR 
Very good partial response 
Vd 
Volume of distribution 
Vss 
Volume of distribution at steady state 
WM 
Waldenstrom’s macroglobulinemia 
WOCBP 
Women of childbearing potential 
 


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Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
NONE 
 
KEYTRUDA 
 
 
LIBTAYO 
 
 
OPDIVO 
 


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12.13. 
Appendix 13: Protocol Amendment History 
The Protocol Amendment Summary of changes Table for the current Amendment 05 is 
located directly before the Table of Contents (TOC). 
Amendment 04 (Sub-study 4) 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 4 are administrative and are mapped in the table below.   
 
Section # for PA3 and Name 
Section # for PA4 and Name 
14.1 
Schedule of Activities Tables 
1.3 
Schedule of Activities (SoA) 
14.2 
Background of Dostarlimab 
2.2 
Background for Dostarlimab  
14.2.1 
Clinical Experience with Dostarlimab 
2.2.1 
Clinical Experience  
14.2.2 
Pharmacokinetic Summary of 
Dostarlimab 
2.2.2 
Pharmacokinetic Summary 
14.2.3 
Safety for Dostarlimab 
2.2.3 
Safety 
8.3.10 
Adverse Events of Special Interest 
14.3.1 
Rationale for the Combination 
2.1 
Rationale for combination of Belantamab 
mafodotin with Dostarlimab 
14.3.2 
Dose justification for Dostarlimab when 
in combination with Belantamab 
Mafodotin 
4.3 
Justification for Dose 
14.3.3 
Potential for Drug-Drug Interactions 
(DDIs) between Belantamab Mafodotin 
and Dostarlimab 
2.2.3.1 
Potential for Drug-Drug Interactions (DDIs) 
between Belantamab Mafodotin and 
Dostarlimab 
14.3.4 
Benefit/Risk 
2.3 
Benefit/Risk Assessment 
14.4 
Study Design Details 
6.2 
Administration of Belantamab mafodotin and 
Dostarlimab  
14.4.1 
Dostarlimab Dosing Frequency 
14.4.2 
Study Intervention(s) Administered - 
Belantamab Mafodotin and Dostarlimab 
14.4.2.2 
Treatment of Overdose 
8.4 
Treatment of Overdose 
14.4.3 
Study Intervention Product and 
Accountability 
6.3 
Preparation/Handling/Storage/Accountability 
– content deleted as it was identical to the 
208887 MP 
14.4.4 
Combination Treatment Belantamab 
Mafodotin (GSK’916) Co-Administered 
with Dostarlimab (GSK’190) 
4.1 
Overall Design 
14.4.5 
Treatment Duration of Dostarlimab 
6.2 
Administration of Belantamab mafodotin and 
Dostarlimab  
14.4.6 
Dose modification for Belantamab 
Mafodotin when in combination with 
Dostarlimab 
6.6 
Dose Modification 
14.4.7 
Inclusion/Exclusion Criteria for 
Dostarlimab Sub-study 
5.1 
Inclusion Criteria for Participants 
5.2 
Exclusion Criteria 
14.4.8 
Management of Pregnancy 
8.3.7 
Management of Pregnancy 
14.5 
References 
10 
References 
14.6 
Appendices 
11 
Guidelines for dose modification and other 
partner combination treatments for all 
substudies 


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Changes listed in the table below are for the Sub-study 4 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 
Changes in Assessments and SoAs 
1.3. Schedule of 
Activities 
Clarified footnote on Single ECG at Screening 
(Table 3) 
Clarified based on prior edits 
(Protocol Amendment 03) 
Extraction of information regarding BM 
Assessments in a separate table (current Table 
6) 
To clarify assessments 
Clarified FISH assessments that are to be 
completed at Screening (Table 6) based on 
availability on previous results 
In line with other protocols in the 
program. 
Added footnote 20c for supportive care 
information (Table 4) 
To align with belantamab mafodotin 
program guidelines 
Added language on biomarker assessments for 
PD-L1 expression (Table 6) 
To clarify biomarker assessments for 
the Sub-study 4 combination  
Clarified language on definition of resolution of 
ophthalmic findings (to baseline instead of Grade 
1) 
To align with GSK belantamab 
mafodotin program language 
8.8 Biomarkers 
Addition of language for prospective evaluation 
of PD-L1 
To clarify assessments for the Sub-
study 4 combination  
Editing, format, style changes 
Throughout 
Correction of typos and technical document 
aspects 
Minor changes; no impact on content 
 
Protocol Amendment 3 (08-JUL-2020) 
Protocol Amendment 03 Summary of Changes Specific to Sub-study 4 
The protocol has been amended to introduce a new sub-study into Section 14 of the 
protocol.   
• Introduction of Substudy 4- Belantamab Mafodotin and dostarlimab (Section 14) 


Signature Page for  208887 TMF-13844075 v1.0
Signature Page for TMF-13844075 v1.0
Reason for signing: Approved
Name: 
Role: Approver
Date of signature: 21-Jan-2022 23:03:29 GMT+0000
PPD

SAP_001.pdf: 
Statistical Analysis Plan
Study ID:  208887 Sub Study 4
Official Title of Sub Study 4: 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 
4 
- 
Belantamab Mafodotin and Dostarlimab (GSK4057190) in Combination
NCT ID of Sub Study 4: NCT06655818
Date of Document: 21-Sept-2022
NCT ID of Master Protocol: NCT04126200


CONFIDENTIAL 
 
 
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1 
 
 
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 4 – Belantamab Mafodotin and 
Dostarlimab (GSK4057190) Combination 
Study Number: 
208887 Sub-study 4 
Compound Number: GSK2857916; Dostarlimab (GSK4057190); 
Abbreviated Title: 
Platform Sub-study of Belantamab Mafodotin (GSK2857916) in 
Combination with Dostarlimab (GSK4057190) in Participants 
with RRMM 
Acronym: 
DREAMM-5 Sub-study 4 
 
Sponsor Name: GlaxoSmithKline Research & Development Limited 
Regulatory Agency Identifier Number(s)  
 
Registry 
 
ID 
Clintrials.gov 
NCT01234567 
 
 
 
Copyright 2022 the GlaxoSmithKline group of companies. All rights reserved.  
Unauthorised copying or use of this information is prohibited. 
 
Information Type: 
Statistical Analysis Plan (SAP) 


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TABLE OF CONTENTS 
PAGE 
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. 
Study Treatment & Sub-group Display Descriptors ........................ 7 
4.1.3. 
Baseline Definition ......................................................................... 7 
4.2. 
Primary Endpoint(s) Analyses ....................................................................... 7 
4.3. 
Secondary Endpoint(s) Analyses .................................................................. 7 
4.3.1. 
Key Secondary Endpoint ............................................................... 8 
4.3.2. 
Secondary Endpoints ..................................................................... 8 
4.4. 
Exploratory Endpoint Analyses ..................................................................... 8 
4.5. 
Safety Analyses ............................................................................................ 8 
4.5.1. 
Extent of Exposure ........................................................................ 8 
4.5.2. 
Adverse Events.............................................................................. 9 
4.5.2.1. 
Adverse Events of Special Interest ............................... 9 
4.5.2.2. 
Inmune-related Adverse Events (irAEs) ........................ 9 
4.5.2.3. 
COVID-19 Assessment and COVID-19 AEs ................. 9 
4.5.2.4. 
Deaths and Serious Adverse Events .......................... 10 
4.5.2.5. 
Adverse Events Leading to Discontinuation of 
Study Treatments and Other Significant 
Adverse Events. ......................................................... 10 
4.5.2.6. 
Pregnancies ............................................................... 10 
4.5.2.7. 
Clinical Laboratory Analysis ........................................ 10 
4.5.3. 
Other Safety Assessments .......................................................... 11 
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 
6.1. 
Appendix 1 Study Population Analyses ....................................................... 12 
6.1.1. 
Participant Disposition ................................................................. 12 
6.1.2. 
Demographic and Baseline Characteristics .................................. 12 
6.1.3. 
Protocol Deviations ...................................................................... 13 
6.1.4. 
Study Intervention Compliance .................................................... 13 
7. 
REFERENCES ....................................................................................................... 14 


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


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208887 Sub-study 4 
 
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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 200887 sub-study 4. For more details about the statistical analysis and plan for the 
overall study refer to the Master SAP. This sub-study was terminated early during the 
Dose Escalation (DE) phase; therefore, this sub-study SAP will focus only on the DE 
phase. 
 
1.1. 
Changes to Protocol Defined Analyses 
Effective October 2021, following an internal prioritization discussion, GSK made the 
decision to close this sub-study during the DE phase. As a result, all analyses 
corresponding to the 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 DE 
phase 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 
Dostarlimab 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 
 


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Objectives 
Endpoints 
Key Secondary 
To evaluate the clinical measures of efficacy of 
belantamab mafodotin and Dostarlimab 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 Dostarlimab 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 Dostarlimab 
in participants with RRMM 
• 
Belantamab mafodotin observed concentration  
To describe the exposure of Dostarlimab when 
administered in combination with belantamab 
mafodotin. 
• 
Combination of belantamab mafodotin with 
Dostarlimab 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 
Dostarlimab, when measured. 
To further determine the safety and tolerability of 
belantamab mafodotin in combination with 
Dostarlimab 
 
 
 
 
 
 
 
 
 
 
• 
AEs of special interest for belantamab 
mafodotin  
• 
AEs of special interest for belantamab 
mafodotin in combination with Dostarlimab 
• 
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 features for the study 
Study 
intervention 
• The Starting Dose (SD) for belantamab mafodotin in study 208887 will be 1.9 
mg/kg Q3W in combination with other anti-cancer treatments but may vary by 
sub-study.  
• Dostarlimab is to be given at least one hour following completion of 
belantamab mafodotin infusion. 
 
Dose Level 
Belantamab 
Mafodotin  
mg/kg IV Q 3 
weeks 
Dostarlimab 
mg IV Q 3 
weeks 
Dostarlimab mg 
IV Q 6 weeks 
1 
1.9 mg/kg 
500 mg, cycles 1 
– 4 
1000 mg, cycle 5 
and every odd 
cycle thereafter 
2 
2.5 mg/kg 
500 mg, cycles 1 
– 4 
1000 mg, cycle 5 
and every odd 
cycle thereafter 
 
• Dostarlimab will be administered as a 30-minute IV infusion at the prescribed 
flat dosing 
 
Time & 
Events 
• Refer to Section 1.3: Schedule of Activities (SoA) in Sub-study 4 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 dostarlimab. 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. 
Study Treatment & Sub-group Display Descriptors  
Phase 
Description 
DE 
1.9mg/kg GSK916 + 500mg Q3W DOSTAR 
1.9mg/kg GSK916 + 1000mg Q6W DOSTAR1 
2.5mg/kg GSK916 + 500mg Q3W DOSTAR1 
2.5mg/kg GSK916 + 1000mg Q6W DOSTAR1 
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. 
 
4.2. 
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.  
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.  


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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 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 Endpoint Analyses 
Analysis of exploratory endpoints will not be performed for neither the DE nor CE phase, 
due to the early termination of the sub-study.  
4.5. 
 Safety Analyses 
The safety analyses will be based on the Safety Analysis Set, unless otherwise specified. 
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.  
A ‘by participant’ 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. 


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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 
Refer to the Master SAP Section 4.5.2.1 for details on AESI. The list of terms and 
reporting requirements for GSK AESI, and the known list of AESIs for GSK’916 can be 
found in Section 8.3.10 of the Sub-Study 4 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 or 3, 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.  
4.5.2.2. 
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.  
4.5.2.3. 
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 3of 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, 


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and COVID-19 AEs by severity, will be obtained from standard AE and SAE summaries 
and listings. 
4.5.2.4. 
Deaths and Serious Adverse Events 
All deaths will be summarised based on the number and percentage of participants. This 
summary will classify participants by time of death relative to the last dose of medication 
(>30 days or 30 days) and primary cause of death (disease under study, SAE related to 
study treatment, or other). A supportive listing will be generated to provide participant-
specific details on participants who died.  
All SAEs associated with belantamab mafodotin monotherapy will be tabulated based on 
the number and percentage of participants who experienced the event. Separate 
summaries will also be provided for study combination treatment-related SAEs. The 
summary tables will be displayed in descending order of total incidence by SOC and PT. 
A study treatment-related SAE (or serious irAE) is defined as an SAE (or serious irAE) 
for which the investigator classifies the relationship to study treatment as “Yes”. A worst-
case scenario approach will be taken to handle missing data, i.e. the summary table will 
include events with the relationship to study treatment as ‘Yes’ or missing.  
4.5.2.5. 
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’190 
(dostarlimab) + 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  
• 
All Treatment-related Serious Adverse Events 
 
4.5.2.6. 
Pregnancies 
Please refer to Section 4.5.2.6 of the MSAP 
4.5.2.7. 
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, haematology changes from baseline, and 
haematology 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.  


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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 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 
Due to the early termination of this sub-study, no POPPK, exploratory biomarker, or 
PK/PD analyses will be conducted. For this sub-study there will also be no health-related 
quality of life analysis or immunogenicity analysis due to early termination. 
4.6.1. 
Pharmacokinetic Analysis 
PK samples will be collected for belantamab mafodotin and/or dostarlimab 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 dostarlimab, 
when measured. 
4.7. 
Interim Analyses 
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 were to be assigned to the 
combination dose level. However, the study was terminated early due to lack of efficacy; 
therefore only  4 participants were enrolled onto dose 1.  
 
6. 
SUPPORTING DOCUMENTATION 
For more supporting documentation for this overall study please refer to Section 6 of the 
Master SAP for more details.  


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6.1. 
Appendix 1 Study Population Analyses 
The study population analyses will be based on the ‘Safety population’ in DE phase and 
‘ITT’ population in CE phase, unless otherwise specified. 
Study population analyses including analyses of participant’s disposition, protocol 
deviations, demographic and baseline characteristics, exposure and treatment compliance 
will be based on GSK Core Data Standards. Details of the planned displays are presented 
in the OPS document. 
6.1.1. 
Participant Disposition 
A summary of the number of participants in each of the analysis populations described in 
Section 3 will be provided. In addition, the number of participants enrolled by country 
and site will be summarized using Enrolled Population. 
A summary of participant status and reason for study withdrawal will be provided. This 
display will show the number and percentage of participants who withdrew from the 
study, including primary reasons for study withdrawal; the number and percentage of 
participants who died, completed the study, and are ongoing for study treatment or follow 
up will also be presented. Reasons for study withdrawal will be presented in the order 
they are displayed in the eCRF. 
In addition, a summary table and listing identifying reasons for screening failures will be 
presented based on the Screened Population. 
A summary of study treatment status will be provided. The display will show the number 
and percentage of participants who are ongoing or discontinued study treatment and a 
summary of the primary reasons for discontinuation of study treatment. Reasons for study 
treatment discontinuation will be presented in the order they are displayed in the eCRF. A 
listing of study treatment discontinuation will be generated. The listing will include last 
dose date and reasons for study treatment discontinuation as well as relatedness to the 
study treatment. 
Screen failures will be summarized and listed. Since screen failures cannot be attributed 
to any one sub-study or phase within a sub-study, repeat reporting may occur in different 
sub-studies. 
6.1.2. 
Demographic and Baseline Characteristics 
The demographic characteristics e.g., age, race, ethnicity, sex, baseline height, and 
baseline body weight will be summarized and listed for Safety population in DE. 
Disease characteristics (e.g. time since initial diagnosis in years, stage at initial diagnosis, 
date of initial diagnosis) at initial diagnosis and screening will be listed and summarised. 
Disease characteristics at screening, including stage, type of multiple myeloma, number 
of prior lines, myeloma light chain and myeloma immunoglobulin, extramedullary 
disease and lytic bone lesion will be summarized and listed. 


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6.1.3. 
Protocol Deviations 
Important protocol deviations will be listed and summarised. Important protocol 
deviations will be based on Safety Population in DE phase and will include 
inclusion/exclusion deviations as well as other deviations. 
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan [8/23/2019., V1.0]. These 
protocol deviations will be reviewed to identify those considered as important as follows: 
• 
Data will be reviewed prior to freezing the database to ensure all important 
deviations (where possible without knowing the study intervention details) are 
captured and categorised in the protocol deviations dataset.  
• 
This dataset will be the basis for the summaries of important protocol 
deviations. 
A separate summary and listing of all inclusion/exclusion criteria deviations will also be 
provided. This summary will be based on data as recorded on the inclusion/exclusion 
page of the eCRF. 
6.1.4. 
Study Intervention Compliance 
Summaries of study treatment exposure and dose modifications (e.g., number of dose 
reductions, number of dose delays/interruptions) will further characterize compliance. 
These analyses are described in Section 4.5.1‘Extent of Exposure’ of the MSAP. 
 
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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.