Clinical trial NCT03828292
Conditions: Multiple Myeloma
Keywords: Antibody drug conjugate Dose-escalation GSK2857916 Japanese Relapsed/Refractory Multiple Myeloma
Sponsor: GlaxoSmithKline
Start date: 2019-03-14; Completion date: 2024-09-05
Enrollment: 15 participants; Allocation: NON_RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
Belantamab mafodotin (GSK2857916) is a first in class, antibody dependent cellular cytotoxicity (ADCC) enhanced, humanized immunoglobulin G1 (IgG1) antibody-drug conjugate (ADC) which binds specifically to B cell maturation antigen (BCMA) expressed on tumor cells of all participants with multiple myeloma. This is a Phase 1, open label, dose escalation study to investigate safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and clinical activity of GSK2857916 when given as monotherapy (Part 1) or given as combination therapy (Part 2). Dose escalation will follow a 3+3 design.

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: Belantamab mafodotin intervention 2: Bortezomib intervention 3: Dexamethasone intervention 4: Pomalidomide
Intervention descriptions: intervention 1: Belantamab mafodotin will be administered as an intravenous infusion. intervention 2: Bortezomib solution for injection will be administered subcutaneously. intervention 3: Dexamethasone tablets will be administered orally. intervention 4: Pomalidomide capsules will be administered orally.

Protocol documents:
Prot_000.pdf: 
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TITLE PAGE 
Protocol Title: A Phase I Open-Label, Dose Escalation Study to Investigate the Safety, 
Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical 
Activity of the Antibody Drug Conjugate GSK2857916 in Japanese Participants with 
Relapsed/Refractory Multiple Myeloma. 
Protocol Number: 207504 
Compound 
Number: 
GSK2857916 
Study Phase: Phase I 
Short Title: A Phase 1 open-label, dose escalation study in Japanese participants with 
relapsed/refractory multiple myeloma who have failed prior anti-myeloma treatments. 
Sponsor Name and Legal Registered Address:  
GlaxoSmithKline K.K. (GSK) 
8-1, Akasaka 1-chome, Minato-ku, Tokyo, 107-0052, Japan 
Medical Monitor Name and Contact Information This information is included in 
Exhibit 1. 
Regulatory Agency Identifying Number:  
None 
Approval Date: 10-Feb-2023 
©2023 GSK group of companies or its licensor.  All rights reserved.  Unauthorised 
copying or use of this information is prohibited. 
 


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SPONSOR SIGNATORY: 
 
 
Mari Matsubara 
 
Medical Affairs Lead (Hematology) 
Oncology Medical and Development 
Japan Medical and DevelopmentGlaxoSmithKline K. K 
 
Date 


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
DNG Number 
Amendment 6 
10-Feb-2023 
RPS-CLIN-050928 
Amendment 5 
12-NOV-2021 
TMF-14042588 
Amendment 4 
15-JAN-2021 
2018N369488_04 
Amendment 3 
01-JUL-2020 
2018N369488_03 
Amendment 2 
05-APR-2019 
2018N369488_02 
Amendment 1 
07-DEC-2018 
2018N369488_01 
Original Protocol 
25-JUL-2018 
2018N369488_00 
 
Amendment 6: 10-Feb-2023 
Overall Rationale for the Amendment: This protocol has been amended to add Post 
Analysis Continued Treatment (PACT) to allow eligible participants to receive study 
treatment after final analysis data cut-off (DCO). 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1 Synopsis 
Section 1.3 Schedule of 
Activities 
Section 4.1 Overall Design 
Section 4.4 EOS Definition 
Section 6.8 Continued Access 
to Study Intervention after the 
End of the Study 
Section 8.3.1 Time Period and 
Frequency for Collecting AE 
and SAE 
Addition of an option for 
PACT to allow eligible 
participants to continue 
study treatment.  
Revised End of Study 
(EOS) definition.  
Addition subsection 6.8.1 
Continued Access to Study 
Intervention After Final 
Analysis DCO prior to EOS. 
Added instructions of the 
scope and the time period 
of data collection and 
reporting during the PACT 
phase. 
To allow continued access to 
study treatment in eligible 
participants and add guidance 
on data collection and reporting 
during the PACT phase 
2.4.1. Risk Assessment 
Updated based on the 
current version of the 
Investigator Brochure 
(v10.0). 
To align with program language 


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Section # and Name 
Description of Change 
Brief Rationale 
6.6.2. Prohibited Medications 
Other Sections 
Updated the wording "anti-
cancer therapy" into "anti-
myeloma therapy" for 
clarification. 
Identified the anti-myeloma 
therapies that is prohibited. 
To align with program level 
language. 
8.6. Pharmacodynamics 
Updated the requirement 
for sample collection after 
effective Amendment 6. 
To update the data collection 
requirement with regards to over 
the program data availability and 
the completion of relevant data 
collected in this study. 
 
 


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TABLE OF CONTENTS 
PAGE  
 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 3 
1. 
PROTOCOL SUMMARY .......................................................................................... 9 
1.1. 
Synopsis ....................................................................................................... 9 
1.2. 
Schema ...................................................................................................... 18 
1.3. 
Schedule of Activities (SoA) ........................................................................ 18 
2. 
INTRODUCTION .................................................................................................... 38 
2.1. 
Study Rationale .......................................................................................... 38 
2.2. 
Background – BCMA and Multiple Myeloma ............................................... 40 
2.3. 
Antibody-Drug Conjugate GSK2857916 ..................................................... 40 
2.3.1. 
Human Experience with GSK2857916 ......................................... 41 
2.3.1.1. 
Studies with GSK2857916 Monotherapy .................... 41 
2.3.1.1.1. 
Safety ..................................................... 42 
2.3.1.2. 
Combination Studies of GSK2857916 ........................ 44 
2.3.1.3. 
Pharmacokinetics and Pharmacodynamics in 
Human........................................................................ 45 
2.4. 
Benefit/Risk Assessment ............................................................................ 47 
2.4.1. 
Risk Assessment ......................................................................... 48 
2.4.2. 
Benefit Assessment ..................................................................... 60 
2.4.3. 
Overall Benefit: Risk Conclusion .................................................. 61 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................... 61 
4. 
STUDY DESIGN .................................................................................................... 62 
4.1. 
Overall Design ............................................................................................ 62 
4.1.1. 
Dose-Limiting Toxicity .................................................................. 66 
4.2. 
Scientific Rationale for Study Design .......................................................... 67 
4.3. 
Justification for Dose .................................................................................. 68 
4.3.1. 
Justification for Dose for Part 1 .................................................... 68 
4.3.2. 
Justification for Dose for Part 2 .................................................... 69 
4.3.2.1. 
GSK2857916 .............................................................. 69 
4.3.2.2. 
Bortezomib/Dexamethasone Dose ............................. 70 
4.3.2.3. 
Pomalidomide/Dexamethasone Dose ......................... 70 
4.4. 
End of Study Definition ............................................................................... 70 
5. 
STUDY POPULATION ........................................................................................... 71 
5.1. 
Inclusion Criteria ......................................................................................... 71 
5.2. 
Exclusion Criteria ........................................................................................ 74 
5.3. 
Lifestyle Considerations .............................................................................. 76 
5.4. 
Screen Failures........................................................................................... 77 
6. 
STUDY TREATMENT ............................................................................................ 77 
6.1. 
GSK2857916 Treatments Administered for Part 1 ...................................... 79 
6.2. 
Treatments Administered for Combination Therapy for Part 2) ................... 79 
6.2.1. 
GSK2857916 with Bortezomib/Dexamethasone (Arm A) 
21-day Cycle ................................................................................ 79 


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6.2.2. 
GSK2857916 with Pomalidomide/Dexamethasone (Arm 
B) 28-day Cycle ........................................................................... 80 
6.3. 
Preparation/Handling/Storage/Accountability .............................................. 81 
6.4. 
Measures to Minimize Bias: Randomization and Blinding ........................... 82 
6.5. 
Study Treatment Compliance ...................................................................... 82 
6.6. 
Concomitant Therapy.................................................................................. 82 
6.6.1. 
Permitted Medications ................................................................. 83 
6.6.2. 
Prohibited Medications ................................................................. 83 
6.6.3. 
Prohibited Device(s) .................................................................... 85 
6.7. 
Dose Modification and Delay ...................................................................... 85 
6.7.1. 
Dose Modification and Delay for Part 1 ........................................ 85 
6.7.2. 
Dose Modification and Delay for Part 2 Arm A ............................. 88 
6.7.2.1. 
GSK2857916 .............................................................. 89 
6.7.2.2. 
Bortezomib ................................................................. 92 
6.7.2.3. 
Dexamethasone ......................................................... 94 
6.7.2.4. 
Guidance on Dose Delays .......................................... 95 
6.7.3. 
Dose Modification and Delay for Part 2 Arm B ............................. 96 
6.7.3.1. 
GSK2857916 .............................................................. 96 
6.7.3.2. 
Pomalidomide ........................................................... 101 
6.7.3.3. 
Dexamethasone ....................................................... 102 
6.7.3.4. 
Guidance on Dose Delays ........................................ 102 
6.7.4. 
Management of Hepatitis B+ participants ................................... 104 
6.7.5. 
Corneal Supportive Care Guideline............................................ 105 
6.8. 
Continued Access to Study Intervention after the End of the Study .......... 105 
6.8.1. 
Continued Access to Study Intervention After Data Cut-off 
prior to EOS ............................................................................... 105 
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ................................................................... 106 
7.1. 
Discontinuation of Study Treatment .......................................................... 106 
7.1.1. 
Discontinuation of Individual Components of Combination 
Study Treatment in Part 2 .......................................................... 107 
7.1.2. 
Liver Chemistry Stopping Criteria .............................................. 107 
7.1.2.1. 
Study Treatment Restart or Rechallenge after 
Liver Stopping Criteria Met ....................................... 108 
7.1.3. 
QTc Interval Stopping Criteria .................................................... 108 
7.1.4. 
Left Ventricular Ejection Fraction (LVEF) Stopping Criteria ........ 108 
7.1.5. 
Corneal Event Stopping Criteria ................................................. 109 
7.1.6. 
Infusion-Related Reaction Management and Stopping 
Criteria ....................................................................................... 109 
7.1.7. 
Allergic and Anaphylactic Reaction Stopping Criteria ................. 109 
7.2. 
Participant Discontinuation/Withdrawal from the Study ............................. 110 
7.3. 
Lost to Follow Up ...................................................................................... 110 
8. 
STUDY ASSESSMENTS AND PROCEDURES ................................................... 111 
8.1. 
Efficacy Assessments ............................................................................... 114 
8.2. 
Safety Assessments ................................................................................. 115 
8.2.1. 
Physical Examinations ............................................................... 115 
8.2.2. 
Ocular Examinations and Procedures ........................................ 115 
8.2.3. 
ECOG Performance Status ........................................................ 116 
8.2.4. 
Vital Signs .................................................................................. 116 
8.2.4.1. 
First Infusion ............................................................. 116 


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8.2.4.2. 
Subsequent Infusions ............................................... 117 
8.2.5. 
Electrocardiograms .................................................................... 117 
8.2.6. 
Echocardiogram......................................................................... 117 
8.2.7. 
Clinical Safety Laboratory Assessments .................................... 117 
8.3. 
Adverse Events and Serious Adverse Events ........................................... 117 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................. 118 
8.3.2. 
Method of Detecting AEs and SAEs ........................................... 120 
8.3.3. 
Follow-up of AEs and SAEs ....................................................... 120 
8.3.4. 
Regulatory Reporting Requirements for SAEs ........................... 120 
8.3.5. 
Adverse Events of Special Interest ............................................ 120 
8.3.6. 
Pregnancy ................................................................................. 121 
8.3.7. 
Cardiovascular and Death Events .............................................. 122 
8.3.8. 
Disease-Related Events and/or Disease-Related 
Outcomes Not Qualifying as SAEs............................................. 122 
8.4. 
Treatment of Overdose ............................................................................. 122 
8.5. 
Pharmacokinetics ..................................................................................... 123 
8.5.1. 
Blood Sample Collection for Pharmacokinetics .......................... 123 
8.5.2. 
Pharmacokinetic Sample Analysis ............................................. 123 
8.6. 
Pharmacodynamics .................................................................................. 124 
8.7. 
Genetics ................................................................................................... 126 
8.9. 
Immunogenicity Assessments ................................................................... 127 
8.10. Evaluation of Anti-Cancer Activity ............................................................. 128 
8.11. Health Economics ..................................................................................... 128 
9. 
DATA MANAGEMENT ......................................................................................... 128 
10. STATISTICAL CONSIDERATIONS ...................................................................... 129 
10.1. Statistical Hypotheses............................................................................... 129 
10.2. Sample Size Determination ...................................................................... 129 
10.3. Populations for Analyses .......................................................................... 129 
10.4. Statistical Analyses ................................................................................... 130 
10.4.1. 
Safety Analyses ......................................................................... 131 
10.4.1.1. Extent of Exposure ................................................... 132 
10.4.2. 
Efficacy Analyses ....................................................................... 132 
10.4.3. 
Immunogenicity Analyses .......................................................... 133 
10.4.4. 
Pharmacokinetic Analyses ......................................................... 133 
10.4.4.1. Concentration-Time Data.......................................... 133 
10.4.4.2. Derived Pharmacokinetic Parameters....................... 133 
10.4.6. 
Genetic Analyses ....................................................................... 134 
10.5. Interim Analyses ....................................................................................... 134 
10.5.1. 
Part 1 ......................................................................................... 134 
10.5.2. 
Part 2 ......................................................................................... 134 
10.5.3. 
Data Monitoring Committee (DMC) ............................................ 135 
CCI
CCI


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11. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................. 135 
11.1. Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations .......................................................................................... 135 
11.1.1. 
Regulatory and Ethical Considerations ...................................... 135 
11.1.2. 
Financial Disclosure ................................................................... 136 
11.1.3. 
Informed Consent ...................................................................... 136 
11.1.3.1. Informed Consent Process ....................................... 136 
11.1.4. 
Data Protection .......................................................................... 137 
11.1.5. 
Committees Structure ................................................................ 137 
11.1.6. 
Dissemination of Clinical Study Data ......................................... 137 
11.1.7. 
Data Quality Assurance ............................................................. 138 
11.1.8. 
Source Documents .................................................................... 138 
11.1.9. 
Study and Site Closure .............................................................. 139 
11.1.10. Publication Policy ....................................................................... 139 
11.1.11. Study Period .............................................................................. 139 
11.1.12. Study Administrative Structure ................................................... 139 
11.2. Appendix 2: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ..................................... 140 
11.2.1. 
Definition of AE .......................................................................... 140 
11.2.2. 
Definition of SAE ........................................................................ 141 
11.2.3. 
Definition of Cardiovascular Events ........................................... 142 
11.2.4. 
Recording and Follow-Up of AE and SAE .................................. 143 
11.2.5. 
Reporting of SAE to GSK ........................................................... 145 
11.3. Appendix 3: Contraceptive Guidance and Collection of Pregnancy 
Information ................................................................................................ 146 
11.3.1. 
Definitions: ................................................................................. 146 
11.3.2. 
Contraception Guidance: ........................................................... 146 
11.3.3. 
Collection of Pregnancy Information: ......................................... 148 
11.4. Appendix 4: Genetics ................................................................................ 150 
11.5. Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments and Study Treatment Rechallenge Guidelines .................... 152 
11.5.1. 
Liver Safety Drug Restart or Rechallenge Guidelines ................ 155 
11.5.1.1. Rechallenge Following Liver Stopping Events 
that are Possibly Related to Study Treatment ........... 155 
11.5.1.2. Restart Following Transient Resolving Liver 
Stopping Events NOT Related to Study 
Treatment ................................................................. 156 
11.6. Appendix 6: ECOG Performance Status ................................................... 158 
11.7. Appendix 7: Corneal Event Severity Grading and Mitigation Strategy ....... 159 
11.8. Appendix 8: Modified Diet in Renal Disease (MDRD) Formula .................. 162 
11.9. Appendix 9: International Myeloma Working Group Uniform 
Response Criteria for Multiple Myeloma ................................................... 163 
11.10. Appendix 10: Abbreviations and Trademarks ............................................ 164 
11.11. Appendix 11: Protocol Amendment History ............................................... 169 
12. REFERENCES ..................................................................................................... 190 
 
 


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1. 
PROTOCOL SUMMARY  
1.1. 
Synopsis  
Protocol Title: A Phase I Open-Label, Dose Escalation Study to Investigate the Safety, 
Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Clinical 
Activity of the Antibody Drug Conjugate GSK2857916 in Japanese Participants with 
Relapsed/Refractory Multiple Myeloma. 
Short Title: A Phase 1 open-label, dose escalation study in Japanese participants with 
relapsed/refractory multiple myeloma who have failed prior anti-myeloma treatments. 
Rationale: Multiple myeloma (MM) is an incurable malignancy and accounts for 1.8% 
of all new cancers and for 13% of all hematologic malignancies. Worldwide, 
approximately 103,000 new cases are diagnosed annually and in the United States (US), 
32,110 new cases and 12,960 deaths are estimated to occur in 2019. Incident cases from 
1990 to 2016 increased by 126% globally. In Japan, the number of patients with MM was 
8,200, and that of deaths was 4,200 in 2017. Due to aging of society, incidence of MM 
has increased recently. Despite the recent advances in therapy, MM remains an incurable 
disease, and novel approaches that induce deep and durable tumor regression with little 
cross-resistance with existing drugs are always needed to expand the therapeutic options 
against MM. 
Over the past two decades, the median survival of patients with MM has significantly 
improved, from 3 to 4 years to approximately 7 to 8 years, mainly due to the application 
of high-dose conventional therapy with autologous stem-cell transplantation 
(HDT-ASCT) as a routine procedure for transplant-eligible MM patients; significant 
improvements in supportive care strategies; and the introduction and wide-spread use of 
the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome 
inhibitor, bortezomib. The survival outcome has significantly improved after the 
introduction of these novel agents. These novel agents nowadays represent the backbone 
of many current standard-of-care therapies for MM patients, both at diagnosis and in the 
relapse setting. 
One such novel therapy, daratumumab is a human IgG1 kappa monoclonal antibody that 
was granted first approval in the US in November 2015, in Japan on 27 September 2017. 
While the data with daratumumab indicate that further prolongation of progression free 
survival (PFS) can be achieved, it is also increasingly recognized that patients continue to 
relapse after treatment with daratumumab, and will need additional treatment options to 
control the disease. 
GSK2857916 is a first in class, antibody-dependent cell-mediated cytotoxicity (ADCC) 
enhanced, humanized IgG1 antibody-drug conjugate (ADC) that binds specifically to 
B-cell maturation antigen (BCMA), a target restricted to B cells at later stages of 
differentiation and expressed on tumor cells of all patients with MM. Upon binding to the 
cell surface, GSK2857916 is rapidly internalized and the active drug (cysteine 
maleimidocaproyl monomethyl auristatin F [cys-mcMMAF]) is released inside the cell. 
The cys-mcMMAF moiety disrupts microtubule networks, leading to cell cycle arrest and 


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apoptosis (ADC mechanism). This dual mechanism of action of GSK2857916 (ADCC 
and microtubule disruption) enables anti-tumor activity on both dividing and non-
dividing cells. In addition, when MM cell lines expressing BCMA are exposed to 
GSK2857916, it may act as an inducer of immunogenic cell death (ICD), representing a 
potential third mechanism of action.  
GSK2857916 has shown strong single-agent activity in the currently ongoing First Time 
in Human (FTIH) study (BMA117159). 
Among the 35 participants in BMA117159 study, receiving GSK2857916 at the 
recommended Phase II dose (RP2D) of 3.4 mg/kg intravenous (IV), once every 3 weeks 
(Q3W), the following results were observed as of 31 August 2018:  
 
Overall response rate (ORR) of 60% [95% confidence interval (CI): 42.1, 76.1] 
 
Median PFS (mPFS) was 12.0 months [95% CI: 3.1, not estimable (NE)]. 
 
The ORR in 32 participants refractory to both IMiDs and proteasome inhibitors 
was 56% (95% CI: 37.7, 73.6), and the mPFS in this subgroup was 7.9 months 
(95% CI: 2.3, NE).   
 
There were no dose limiting toxicities (DLTs) reported at doses up to 4.6 mg/kg; 
however the dose of 4.6 mg/kg was considered not tolerated. Most events were 
Grade 1/2. Overall, GSK2857916 was well tolerated and adverse events were 
manageable. 
This data supports testing of GSK2857916 as a monotherapy in Japanese participants 
with relapsed/refractory multiple myeloma (RRMM). 
In addition, given the strong single-agent activity of GSK2857916, the combination 
therapy of GSK2857916 with standard of care (SoC) agents is an attractive option to 
explore for patients with RRMM.  Based on the mechanism of action of GSK2857916, 
the combination with SoC therapies (bortezomib and dexamethasone [Bor/Dex] or 
pomalidomide and dexamethasone [Pom/Dex]) is expected to result in additive, or 
potentially synergistic effects which could potentially translate into a deep and long-
lasting response over what has been achieved with available agents. 
The ongoing Phase I/II open-label, dose escalation and expansion study 207497 is 
evaluating the safety and clinical activity of GSK2857916 when given in combination 
with Bor/Dex in participants with RRMM who have received at least 1 prior line of 
therapy.  Preliminary data from this study indicate that the combination of GSK2857916 
at 2.5 mg/kg dose with Bor/Dex is safe and tolerable without DLTs and is showing early 
evidence of activity, given the prior and ongoing experience (from FTIH study 
BMA117159 and Phase II 205678 study) of single agent activity for this dose 
(2.5 mg/kg) of GSK2857916. 
GSK2857916 at multiple dose levels in combination with Pom/Dex once every 4 weeks 
(Q4W) is being evaluated for safety and efficacy in patients with RRMM in an ongoing 
Phase I/II study conducted by the Myeloma Canada Research Network (MCRN 007 or 
study 209418).  As of 01 February 2020, 11 participants have received GSK2857916 at 


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1.92 mg/kg dose, and 7 participants at 2.5 mg/kg dose in combination with Pom/Dex 
Q4W.  Preliminary data showed that the GSK2857916/Pom/Dex combination at both 
dose levels has resulted in early signs of clinical activity, and an acceptable safety profile, 
consistent with the known safety profile of the individual components, GSK2857916 and 
Pom/Dex. 
These data support testing GSK2857916 when administered in combination with 
approved regimens of either Bor/Dex (Arm A) or Pom/Dex (Arm B) in Japanese 
participants with RRMM in Part 2. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Primary Objective 
To evaluate safety, tolerability of GSK2857916 in 
Japanese participants RRMM. 
Number of participants with DLTs 
Adverse events (AEs) and changes in clinical signs and 
laboratory parameters. 
Secondary Objectives 
To evaluate pharmacokinetic (PK) profile of 
GSK2857916 and cysteine maleimidocaproyl 
monomethyl auristatin F (cys-mcMMAF) after IV single 
and repeat dose administration in Japanese participants 
with RRMM. 
GSK2857916 and cys-mcMMAF PK parameters 
following IV single and repeat dose administration as 
data permit (e.g., AUCs, Cmax, tmax, CL, Vss, t½ 
[single dose], Ceoi, Ctrough, and Rac (Ceoi and 
Ctrough) [repeat dose]). 
To assess anti-drug antibody (ADA) formation after IV 
single and repeat dose administration of GSK2857916. 
ADA incidence and titers after IV single and repeat 
dosing of GSK2857916. 
To investigate the initial anti-tumor activity of 
GSK2857916 in Japanese participants with RRMM. 
Clinical activity measured as Overall Response Rate 
(ORR) and Clinical Benefit Rate (CBR) which are 
defined as follows: 
 ORR: the percentage of participants achieving 
confirmed partial response or better (PR) 
 CBR: the percentage of participants with minimal 
response (MR) or better 
Overall Design: 
This is a Phase 1, open label, dose escalation study to investigate safety, tolerability, 
pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity and clinical activity of 
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GSK2857916 when given as monotherapy on a once every 21 days schedule (Part 1), or 
given in combination with Bor/Dex on a once every 21 days schedule (Part 2 Arm A) or 
with Pom/Dex on a once every 28 days schedule (Part 2 Arm B).  The study will consist 
of 2 parts.  Part 1 is a dose escalation phase to evaluate the safety and tolerability of up to 
2 dose levels of GSK2857916 monotherapy.  Part 2 of the study will evaluate the safety 
and tolerability of 1 dose level of GSK2857916 in combination with 2 SoC regimens: 
Part 2 Arm A – GSK2857916 with Bor/Dex, and Part 2 Arm B – GSK2857916 with 
Pom/Dex. 
The dose escalation model is based on 3 + 3 design.  The GSK2857916 will be 
administered IV over 30 min infusion once every 3 weeks (21 days = 1 cycle) or every 
4 weeks (28 days = 1 cycle).  The initial anti-tumor activity of GSK2857916 based on 
response assessment criteria as defined by International Myeloma Working Group 
(IMWG) 2016 will also be assessed during the study [Kumar, 2016]. 
Disclosure Statement: This is an open-label study; no masking. 
Number of Participants: 
The maximum number of participants for Part 1 will be up to 12, up to 6 participants each 
for 2.5 mg/kg cohort and 3.4 mg/kg cohort based on 3 + 3 design.  The maximum number 
of participants for Part 2 will be up to 12, up to 6 participants each for Arm A and Arm B 
based on 3 + 3 design.  If participants prematurely discontinue during the DLT evaluation 
period for reasons other than toxicity, additional participants may be enrolled as 
replacement participants and assigned to the same dose level at the discretion of the 
Sponsor and in consultation with the Investigator. 
Intervention Groups and Duration: Study treatment is defined as any investigational 
intervention intended to be administered to a study participant according to the study 
protocol. GSK2857916 will be administered IV over 30 minutes on Day 1 of each cycle. 
Premedication is not required prior to infusion unless deemed medically necessary by the 
investigator, in which case it should be administered according to institutional 
recommendations.  Any participant experiencing an infusion-related reaction (IRR) must 
receive appropriate medical treatment. When the participant’s condition is stable, the 
infusion may be restarted at a slower rate. 
Participants will be treated until disease progression, withdrawal of consent or until 
unacceptable toxicity. 
Inclusion Criteria: Participants are eligible to be included in the study only if all of the 
following criteria apply: 
1. Provide signed written informed consent, which includes compliance with the 
requirements and restrictions listed in the consent form 
2. Male or female, 20 years or older (at the time consent is obtained) 
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 


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4. Histologically or cytologically confirmed diagnosis of MM as defined according to 
IMWG 2014 [Rajkumar, 2014], criteria in a participant who fulfills all of the 
following: 
i. 
has undergone stem cell transplant, or is considered transplant ineligible, 
ii. 
Part 1: has received at least 2 prior lines of anti-myeloma drugs containing at 
least 1 proteasome inhibitor and at least 1 immunomodulator, 
Part 2: has received at least 1 prior line of anti-myeloma drugs, 
iii. 
Part 1: has demonstrated progression on, or within 60 days of completion of 
the last therapy. 
Part 2: has documented disease progression during or after their most recent 
therapy. 
5. Has measurable disease with at least one of the following: 
a. Serum M-protein ≥0.5 g/dL (≥ 5 g/L) 
b. Urine M-protein ≥200 mg/24h 
c. Serum free light chain (FLC) assay: Involved FLC level ≥ 10 mg/dL (≥100 mg/L) 
 
and an abnormal serum FLC ratio (<0.26 or >1.65). 
6. Participants with a history of autologous stem cell transplant are eligible for study 
participation provided the following eligibility criteria are met: 
a. Transplant was > 100 days prior to study enrolment 
b. No active infection. 
7. Female Participants: Contraceptive use by women should be consistent with local 
regulations regarding the methods of contraception for those participating in clinical 
studies. 
A female participant is eligible to participate if she is not pregnant or breastfeeding 
and at least one of the following conditions applies: 
 
Is not a woman of childbearing potential (WOCBP) 
OR 
 
For Part 1 and Part 2 Arm A: 
Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of <1% per year), preferably with low user dependency, during the 
treatment period and for 4 months after the last dose of GSK2857916, and 
7 months from the last dose of bortezomib (only Part 2 Arm A), and agrees not 
to donate eggs (ova, oocytes) for the purpose of reproduction during this period. 
The investigator should evaluate the effectiveness of the contraceptive method 
in relationship to the first dose of study treatment. 
A WOCBP must have a negative highly sensitive serum pregnancy test (as 
required by local regulations) within 72 hours before the first dose of study 
treatment and agree to use effective contraception during the study and for 
4 months after the last dose of GSK2857916, and 7 months from the last dose of 
bortezomib (only Part 2 Arm A). 


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For Part 2 Arm B: 
Due to pomalidomide being a thalidomide analogue with risk for embryo-fetal 
toxicity and prescribed under a restricted distribution program, WOCBP 
participants will be eligible if they commit either to abstain continuously from 
heterosexual sexual intercourse or to use 2 methods of reliable birth control, 
beginning 4 weeks prior to initiating treatment with pomalidomide, during 
therapy, during dose interruptions and continuing for 4 weeks following 
discontinuation of pomalidomide treatment.  Thereafter, WOCBP participants 
must use a contraceptive method that is highly effective (with a failure rate of 
<1% per year) for a further 3 months, and agrees not to donate eggs (ova, 
oocytes) for the purpose of reproduction during this period. 
Two negative pregnancy tests must be obtained prior to initiating pomalidomide 
therapy.  The first test should be performed within 10 to 14 days and the second 
test within 24 hours prior to prescribing pomalidomide therapy. 
The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
8. Male Participants: Contraceptive use by men should be consistent with local 
regulations regarding the methods of contraception for those participating in clinical 
studies.  
Male participants are eligible to participate if they agree to the following from the 
time of first dose of study treatment until 6 months after the last dose of 
GSK2857916, 4 months after the last dose of bortezomib (only Part 2 Arm A), and 
4 weeks after the last dose of pomalidomide (only Part 2 Arm B) to allow for 
clearance of any altered sperm:  
 
Refrain from donating sperm 
PLUS either: 
 
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long term and persistent basis) and agree to remain abstinent.  
OR 
 
Must agree to use contraception/barrier as detailed below: 
Agree to use a male condom, even if they have undergone a successful vasectomy, 
and female partner to use an additional highly effective contraceptive method with a 
failure rate of <1% per year as when having sexual intercourse with a woman of 
childbearing potential (including pregnant females) 
9. All prior treatment-related toxicities (defined by National Cancer Institute- Common 
Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03, must be ≤Grade 1 
at the time of enrolment except for alopecia.  Participants with Grade 2 peripheral 
neuropathy can be enrolled into Part 1 and Part 2 Arm B but not into Part 2 Arm A. 
10. Adequate organ system functions as defined in Table 10 or Table 11. 


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Exclusion Criteria: Participants are excluded from the study if any of the following 
criteria apply: 
1. Systemic anti-tumor-therapy within 14 days, or plasmapheresis within 7 days prior to 
the first dose of study treatment. 
2. Symptomatic amyloidosis, active ‘polyneuropathy, organomegaly, endocrinopathy, 
myeloma protein, and skin changes’ (POEMS) syndrome, active plasma cell 
leukemia at the time of screening. 
3. Use of an investigational drug within 14 days or 5 half-lives, whichever is shorter, 
preceding the first dose of study treatment.  Prior treatment with a monoclonal 
antibody within 30 days of receiving the first dose of study treatment. Prior BCMA 
targeted therapy. 
4. History of an allogeneic stem cell transplant. 
5. Current use of prohibited medications/device or planned use of any of these during 
the study period. 
6. Current corneal epithelial disease except mild punctate keratopathy. 
7. Presence of active renal condition (infection, requirement for dialysis or any other 
condition that could affect participant’s safety). Participants with isolated proteinuria 
resulting from MM are eligible, provided they fulfil criteria given in Table 10 or 
Table 11. 
8. Evidence of active mucosal or internal bleeding. 
9. Any major surgery within the last 4 weeks. 
10. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other 
conditions (including laboratory abnormalities) that could interfere with participant’s 
safety, obtaining informed consent or compliance to the study procedures. 
11. Active infection requiring treatment (antibiotic, antiviral, or antifungal treatment). 
12. Evidence of severe or uncontrolled systemic diseases. 
13. Malignancies other than disease under study are excluded, except for any other 
malignancy from which the participant has been disease-free for more than 2 years 
and, in the opinion of the investigators and Medical Monitor, will not affect the 
evaluation of the effects of this clinical study treatment on the currently targeted 
malignancy (MM). 
14. Evidence of cardiovascular risk including any of the following: 
a. QTcF interval ≥470 msecs (the QT interval values must be corrected for heart rate 
 
by Fridericia’s formula [QTcF]). 
b. Evidence of current clinically significant uncontrolled arrhythmias, including 
 
clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd 
 
degree atrioventricular (AV) block. 
c. History of myocardial infarction, acute coronary syndromes (including unstable 
 
angina), coronary angioplasty, or stenting or bypass grafting within 6 months of 
 
Screening. 


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d. Class III or IV heart failure as defined by the New York Heart Association 
 
functional classification system. 
e. Uncontrolled hypertension. 
15. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs 
chemically related to GSK2857916 or any of the components of the study treatment. 
16. Pregnant or lactating female or female who are interrupting lactation. 
17. Known human immunodeficiency virus (HIV) infection. 
18. Patients with Hepatitis B will be excluded unless the following criteria can be met. 
Serology 
Screening 
During Study Treatment 
 
Hepatitis B surface 
antibody (HBsAb) + 
and/or Hepatitis B core 
antibody (HBcAb) + 
AND 
 
Hepatitis B surface 
antigen (HBsAg) - 
 HBV DNA undetectable 
 Monitoring per protocol 
(Table 4) 
 Antiviral treatment 
instituted if HBV DNA 
becomes detectable 
Note: Participants with positive HBsAb alone due to hepatitis B vaccination can be 
enrolled. 
19. Positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid 
(RNA) test result at screening or within 3 months prior to first dose of study 
treatment. 
Note: Participants with positive hepatitis C antibody due to prior resolved disease 
can only be enrolled, if a confirmatory negative hepatitis C RNA test is obtained. 
Note: Hepatitis RNA testing is optional and participants with negative Hepatitis C 
antibody test are not required to also undergo hepatitis C RNA testing. 
20. Current unstable liver or biliary disease per investigator assessment defined by the 
presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or 
gastric varices, persistent jaundice, or cirrhosis. 
Note: Stable chronic liver disease (including Gilbert’s syndrome or asymptomatic 
gallstones) or hepatobiliary involvement of malignancy is acceptable if participant 
otherwise meets entry criteria. 
21. Previously diagnosed with interstitial lung disease or current complication of 
interstitial lung disease. 
Additional Exclusion Criteria for Part 2 Arm A 
22. Intolerant to bortezomib or refractory to bortezomib. 
23. Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain. 
24. Intolerance or contraindications to herpes zoster prophylaxis. 


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Additional Exclusion Criteria for Part 2 Arm B 
25. Prior pomalidomide use. 
26. Intolerance or contraindications to antithrombotic prophylaxis. 
27. Active or history of venous thromboembolism within 3 months prior to first dose of 
study treatment. 
Data Monitoring Committee: No 
 
End of Study Definition:  
Following 21 months post last subject first dose, Study 207504 (DREAMM-11) will 
move into the PACT phase where the study remains open to provide continued access to 
study treatment for study participants who are continuing to derive clinical benefit. At 
that time, the collection of new data for participants who no longer receive study 
treatment will stop entirely and the clinical trial database will be closed. Those 
participants still benefiting from study drug in the opinion of their treating physician may 
continue to receive study drug and only SAEs, AEs leading to treatment discontinuation, 
overdose and pregnancy cases, and pre-specified ocular data will be reported directly to 
GSK. The EOS is defined as the date of the last visit of the last participant in the study 
(e.g. last dose plus 70 days AE reporting period) or last scheduled procedure shown in the 
Schedule of Activities for the last participant in the study. 
 


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1.2. 
Schema  
Study Schematic 
 
1.3. 
Schedule of Activities (SoA)  
All assessments planned for participants in Part 1 of study 207504 are shown inTable 1.  All assessments planned for participants in Part 2 
Arm A and Arm B are shown in Table 2 and Table 3, respectively. 
The details of these assessments are provided in footnotes to the table and Section 8. 
PACT Phase: Participants who continue to receive study treatment during the PACT phase will be monitored and receive follow-up care 
in accordance with standard local clinical practice. Assessments will revert to the standard of care at a patient’s particular study site and 


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only SAEs, AEs leading to discontinuation of study treatment, prespecified ocular data, overdoses and pregnancy cases will be reported 
directly to the Sponsor via paper forms (see Section 4.4 and Section 8.3.1).  


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Table 1 
Schedule of Activities for Part 1 (GSK2857916 Monotherapy)  
Time and Time Table (Cycle=21 days) 
Study Assessment1 
Screen2 
D1 
C1 
D2 
C1 
D8 
C1 
D15 
C1 
D1 
C2 to CX 
End of 
Treatment 
Visit3 
Follow-up Visit 
Informed Consent 
X 
 
 
 
 
 
 
 
Baseline Demographics 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Physical Examination 
X 
X 
 
 
 
X 
X 
 
Ocular Examination 
X4 
 
 
 
 
X5 
X6 
X6 
ECOG Performance Status 
X 
X 
 
 
 
X 
X 
 
Vital Signs (BP, HR, Body 
Temperature) 
X 
X7 
 
X 
X 
X7 
X 
 
Weight and Height 
X 
Weight 
Only 
 
 
 
Weight Only 
Weight Only 
 
Hematology 
X 
X8 
 
X 
X 
X 
X 
 
Clinical chemistry 
X 
X8 
X 
X 
X 
X 
X 
 
Urine Dipstick 
X 
X8 
 
 
 
X 
X 
 
eGFR9 
X 
X 
 
 
 
X 
X 
 
Spot urine for Albumin /creatinine 
ratio10 
X 
X 
 
 
 
X 
X 
 
HBV/HCV tests 
X 
 
 
 
 
 
 
 
Troponin11, BNP11 
X 
 
 
 
 
 
 
 
UPEP and urine Immunofixation 
X 
 
 
 
 
X 
X 
 


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Time and Time Table (Cycle=21 days) 
Study Assessment1 
Screen2 
D1 
C1 
D2 
C1 
D8 
C1 
D15 
C1 
D1 
C2 to CX 
End of 
Treatment 
Visit3 
Follow-up Visit 
SPEP and serum 
Immunofixation, Serum M-protein 
Calculation 
X 
 
 
 
 
X 
X 
 
Kappa, lambda FLC, FLC Ratio 
X 
 
 
 
 
X 
X 
 
24 hour urine protein  
X 
 
 
 
 
X 
X 
 
Calcium corrected for albumin 
(serum) 
X 
 
 
 
 
X 
X 
 
IgG, IgM, IgA 
X 
 
 
 
 
X 
X 
 
IgD/E12 
X 
 
 
 
 
X 
X 
 
CRP 
X 
 
 
 
 
X 
X 
 
Beta2 microglobulin 
X 
 
 
 
 
X 
 
 
Pregnancy Test13 
X 
X 
 
 
 
X 
X 
X 
Skeletal survey14 
X 
As clinically indicated 
 
Chest X-ray imaging 
X 
As clinically indicated 
X 
 
12-lead ECG15 
X 
X 
 
 
 
 
X 
 
LVEF (ECHO)16 
X 
 
 
 
 
 
X 
 
Extramedullary plasmacytoma 
Imaging17 
X 
 
 
 
 
C5, C9, C13, 
And later only if 
clinically 
indicated 
X18 
 
FISH testing19 
X 
 
 
 
 
 
 
 


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Time and Time Table (Cycle=21 days) 
Study Assessment1 
Screen2 
D1 
C1 
D2 
C1 
D8 
C1 
D15 
C1 
D1 
C2 to CX 
End of 
Treatment 
Visit3 
Follow-up Visit 
BM aspirate/biopsy for disease 
assessment 
X20 
 
 
 
 
At the time of 
CR or at time of 
suspected 
Progressive 
disease (only if 
not evident 
otherwise) 
Only if CR has 
been achieved 
by this visit, or 
suspected 
Progressive 
disease not 
evident 
otherwise 
 
Serum (anti-drug-antibodies)22 
 
X 
 
 
 
C2, C3, C6, C9, 
C12, C16 
X 
 
Serial Pharmacokinetics 
(blood) 
 
X23 
X23 
X23 
X23 
X23 
X24 
 
Genetics Sample25 
X 
 
Premedication if needed 
 
X 
 
 
 
X 
 
 
GSK2857916 administration26 
 
X 
 
 
 
X 
 
 
Preservative-free Artificial Tears 
 
Administered in each eye at least 4-8 times daily beginning on C1D1 until EOT.  In the event of ocular 
symptoms (i.e., dry eyes), the use of artificial tears may be increased up to every 2 hours, as needed. 
 
Cooling Eye Masks (optional) 
 
On GSK2857916 dosing day, may apply cooling eye masks as long as tolerated from start of infusion and up to 
4 hours 
 
Adverse Events27 
X 
Continuous 
X 
Concomitant Medications27 
X 
X 
New anti-myeloma Therapy28 
 
 
 
 
 
 
 
X 
CCI


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1. 
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified. All other assessments can be performed 
within ±3 days of scheduled occurrence unless otherwise specified. For C1D2 assessments, no time window is permitted. C1D8 and C1D15 assessments can be 
performed within ±1 day of scheduled occurrence. 
2. 
All Screening assessments must be performed within 21 days prior to first dose unless otherwise specified. Informed Consent must be signed before any 
study-specific assessments are performed. 
3. 
The End of Treatment (EOT) will occur within 30 days (±3 days) after the last dose of any study medication or before the initiation of any other antimyeloma 
treatment. For participant discontinuing treatment in the PACT phase, no end of treatment visit is required. 
4. 
Screening ocular examination will be performed by an ophthalmologist within 21 days prior to the first dosing (see Section 8.2.2 for the list of screening 
ophthalmic exam procedures). 
5. 
On-study ophthalmic exams to be performed by an ophthalmologist every 3 weeks. See Section 8.2.2 for the list of ophthalmic exam procedures. If there are no 
corneal signs per the GSK scale at time of the C4 exam, participants may have their ophthalmologic exams decreased to once every 3 months. If a participant 
subsequently develops ocular symptoms, the participant should be evaluated by an ophthalmologist. Intraocular pressure must be monitored if steroid eye drops 
are used continuously more than 7 days. Additional exams may be performed by the ophthalmologist, as clinically indicated. 
6. 
Ophthalmic exam at the EOT to be performed by an ophthalmologist. Participants with corneal signs per the GSK scale at the EOT Visit will continue to be 
followed at 3 weeks (7 days) after the EOT visit and then every 6 weeks (7 days) for up to 12 months, or until full resolution of findings defined as a return to 
participant’s baseline or deemed clinically stable by an ophthalmologist, whichever comes first. See Section 8.2.2 for the list of ophthalmic exam procedures. 
7. 
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes (5 minutes), EOI (5 minutes), and 
1 hour post EOI (5 minutes). On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI). The Sentinel Participant 
must be observed for at least 24 hours post EOI. On days where vital sign timepoints align with PK sampling timepoints, vital signs should be assessed prior to 
PK samples being drawn. 
8. 
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on C1D1. Refer to Table 32 for comprehensive list of laboratory tests. 
9. 
eGFR is to be calculated via modified diet in renal disease (MDRD) calculation. 
10. Albumin/creatinine ratios (spot urine from first void) at screening, C1, and every cycle thereafter. 
11. Troponin I or T and B-type natriuretic peptide (BNP) will be measured at the local laboratory, or by central laboratory if not available locally.  If cardiac workup 
is required due to safety concerns during the study, troponin I or T and BNP should be measured as clinically indicated. 
12. Only in patients with IgD/IgE myeloma. 
13. Perform only in women of child-bearing potential (WOCBP), see Appendix 3 for definition.  A serum pregnancy test must be performed at screening; if the test 
is completed within 72 hours prior to the first dose of GSK2857916, this assessment does not have to be repeated on C1D1.  For questionable cases, 
follicle-stimulating hormone (FSH) and estradiol (as needed in WOCBP) should be performed at local lab to determine childbearing potential.  WOCBP must 
have a negative highly sensitive serum pregnancy test within 72 hours of dosing on C1D1.  Subsequent pregnancy tests on dosing days may be either serum or 


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urine.  Final pregnancy test (serum or urine) must be performed in WOCBP at the EOT Visit.  Follow up pregnancy assessment by telephone (for WOCBP only) 
should be performed 4 months after the last dose of GSK2857916. 
14. Skeletal Survey: Imaging of bones for lytic lesions by a method aligned with the institutional guidance (X-ray, CT, or MRI). Skeletal survey results within 
30 days prior to C1D1 are acceptable. 
15. On dosing days, ECG to be performed in singlet at predose (within 30 minutes prior to SOI). 
16. Echocardiography for left ventricular ejection fraction (LVEF) performed within 35 days prior to first dose is acceptable as screening value. 
17. Imaging is only required for participants with extramedullary disease (CT, MRI, or PET/CT can be applied per local guidance). Screening assessment may be 
performed up to 30 days prior to C1D1. The same modality should be used throughout the study (i.e., if CT scan was used as baseline, participant needs to be 
followed by CT scans). Plasmacytoma measurements should be taken from the CT portion of the PET/CT, or MRI scans, or dedicated CT scans where 
applicable. For participants with skin only involvement, skin lesions should be measured with a ruler. Measurement of tumor size will be determined by the Sum 
of the Products of the maximal perpendicular diameters of measured lesions (SPD). 
18. In participants with extramedullary plasmacytoma, if the last radiographic assessment occurred ≥8 weeks prior to the participant’s withdrawal from study 
treatment, and progressive disease has NOT been documented, –a new assessment for extramedullary disease should be obtained at the EOT. 
19. FISH testing at least for: t(4;14), t(14;16), 17p13del. FISH results from samples taken within 60 days prior to first dose are acceptable. 
20. Archival tissue from up to 60 days prior to study is acceptable. 
22. All ADA samples will be collected prior to each infusion. If a dose is delayed at C2, an ADA sample should be collected on a planned dosing day at C2 
(21 [±3] days post dose on C1D1) (sample collection is not needed when a dose is delayed at or after C3). 
23. PK samples to be taken (in all the study participants) for both GSK2857916 and cys-mcMMAF measurement: C1D1 at pre-dose (within 30 minutes prior to 
SOI), at EOI (just before EOI), 1 hour after EOI, 3 hours after EOI (±5 minutes), 8 hours after EOI (±15 minutes), 24 hours after EOI (±1hour) (D2); C1D8, 
1 sample; C1D15, 1 sample; on C2D1, C3D1, C6D1, C9D1, and C12 D1, at pre-dose (within 30 minutes prior to SOI) and at the EOI (just before EOI); on 
C16D1 at pre-dose (within 30 minutes prior to SOI). If a dose is delayed at C2, a PK sample should be collected on a planned dosing day at C2 (21 [±3] days 
post dose on C1D1) (sample collection is not needed when a dose is delayed at or after C3). 
24. Collect 1 PK sample at each participants’ final visit. 
25. Informed consent for optional genetics research should be obtained before collecting a sample. The sample will be collected between the first opportunity after a 
participant has met all eligibility requirements and the EOT Visit. 
26. Study treatment administration ±3 day window only. 
CCI


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27. Any SAEs assessed as related to study participation or related to a GSK product will be recorded from the time a participant consent through any follow up.  
AEs and SAEs will be collected throughout the study until 70 days after the last dose of study treatment regardless of initiation of new anti-myeloma therapy.  
Concomitant medications administered after the EOT should only be recorded for SAEs/AESIs. 
28. New anticancer therapy will be recorded through any follow up. 


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Table 2 
Schedule of Activities for Part 2 Arm A (GSK2857916 in Combination with Bortezomib plus Dexamethasone)  
Time and Time Table (Cycle=21 days) 
Study Assessment1 
Screen2 
D1 
C1 to C8 
D4 
C1 to C8 
D8 
C1 to C8 
D11 
C1 to C8 
D1 
C9 to CX 
End of 
Treatment 
Visit3 
Follow-up Visit 
Informed Consent 
X 
 
 
 
 
 
 
 
Baseline Demographics 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Physical Examination 
X 
X 
 
 
 
X 
X 
 
Ocular Examination 
X4 
X5 
 
 
 
X5 
X6 
X6 
ECOG Performance Status 
X 
X 
 
 
 
X 
X 
 
Vital Signs (BP, HR, Body 
Temperature)7 
X 
X8 
If clinically indicated 
X8 
X 
 
Weight and Height 
X 
Weight 
Only 
 
 
 
Weight Only 
Weight Only 
 
Hematology7 
X 
X9 
X 
X 
X 
X 
X 
 
Clinical chemistry 
X 
X9 
X 
X 
X 
X 
X 
 
Urine Dipstick 
X 
X9 
 
 
 
X 
X 
 
eGFR10 
X 
X 
 
 
 
X 
X 
 
Spot urine for Albumin /creatinine 
ratio11 
X 
X 
 
 
 
X 
X 
 
HBV/HCV tests 
X 
 
 
 
 
 
 
 
Troponin12, BNP12 
X 
 
 
 
 
 
 
 
UPEP and urine 
Immunofixation13 
X 
X 
 
 
 
X 
X 
 


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Time and Time Table (Cycle=21 days) 
Study Assessment1 
Screen2 
D1 
C1 to C8 
D4 
C1 to C8 
D8 
C1 to C8 
D11 
C1 to C8 
D1 
C9 to CX 
End of 
Treatment 
Visit3 
Follow-up Visit 
SPEP and serum 
Immunofixation, Serum M-protein 
Calculation13 
X 
X 
 
 
 
X 
X 
 
Kappa, lambda FLC, FLC Ratio13 
X 
X 
 
 
 
X 
X 
 
24 hour urine protein13 
X 
X 
 
 
 
X 
X 
 
Calcium corrected for albumin 
(serum)13 
X 
X 
 
 
 
X 
X 
 
IgG, IgM, IgA13 
X 
X 
 
 
 
X 
X 
 
IgD/E13, 14 
X 
X 
 
 
 
X 
X 
 
CRP13 
X 
X 
 
 
 
X 
X 
 
Beta2 microglobulin13 
X 
X 
 
 
 
X 
 
 
Pregnancy Test15 
X 
X 
 
 
 
X 
X 
X 
Skeletal survey16 
X 
As clinically indicated 
 
Chest X-ray imaging 
X 
As clinically indicated 
X 
 
12-lead ECG17 
X 
C1D1 only 
 
 
 
 
X 
 
LVEF (ECHO)18 
X 
 
 
 
 
 
X 
 
Extramedullary plasmacytoma 
Imaging19 
X 
C5, C9, 
C13, 
And later 
only if 
clinically 
indicated 
 
 
 
C5, C9, C13, 
And later only if 
clinically 
indicated 
X20 
 
FISH testing21 
X 
 
 
 
 
 
 
 


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Time and Time Table (Cycle=21 days) 
Study Assessment1 
Screen2 
D1 
C1 to C8 
D4 
C1 to C8 
D8 
C1 to C8 
D11 
C1 to C8 
D1 
C9 to CX 
End of 
Treatment 
Visit3 
Follow-up Visit 
BM aspirate/biopsy for disease 
assessment 
X22 
At the time 
of CR or at 
time of 
suspected 
Progressive 
disease 
(only if not 
evident 
otherwise) 
 
 
 
At the time of 
CR or at time of 
suspected 
Progressive 
disease (only if 
not evident 
otherwise) 
Only if CR has 
been achieved 
by this visit, or 
suspected 
Progressive 
disease not 
evident 
otherwise 
 
Serum (anti-drug-antibodies)23 
 
X (See 
Section 
8.9) 
 
 
 
X (See 
Section 8.9) 
X 
 
Pharmacokinetic blood sampling 
for GSK285791623 
 
X (See Table 34) 
 
Genetics Sample24 
X 
 
Premedication if needed 
 
X 
 
 
 
X 
 
 
GSK2857916 administration25 
 
X 
 
 
 
X 
 
 
Bortezomib administration26 
 
X 
X 
X 
X 
 
 
 
Dexamethasone administration27 
 
D1, D2, D4, D5, D8, D9, D11 and D12 of each 21-day cycle  
 
 
 
Preservative-free Artificial Tears 
 
Administered in each eye at least 4-8 times daily beginning on C1D1 until EOT.  In the event of ocular 
symptoms (i.e., dry eyes), the use of artificial tears may be increased up to every 2 hours, as needed. 
 
Cooling Eye Masks (optional) 
 
On GSK2857916 dosing day, may apply cooling eye masks as long as tolerated from start of infusion and up to 
4 hours 
 
Adverse Events28 
X 
Continuous 
X 
CCI


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Time and Time Table (Cycle=21 days) 
Study Assessment1 
Screen2 
D1 
C1 to C8 
D4 
C1 to C8 
D8 
C1 to C8 
D11 
C1 to C8 
D1 
C9 to CX 
End of 
Treatment 
Visit3 
Follow-up Visit 
Concomitant Medications28 
X 
X 
New anti-myeloma Therapy29 
 
 
 
 
 
 
 
X 
1. 
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be performed 
within ±3 days of scheduled occurrence unless otherwise specified.  D4, D8, and D11 assessments can be performed within ±1 day of scheduled occurrence. 
2. 
All Screening assessments must be performed within 21 days prior to first dose unless otherwise specified.  Informed Consent must be signed before any 
study-specific assessments are performed. 
3. 
The End of Treatment (EOT) will occur within 30 days (±3 days) after the last dose of any study medication or before the initiation of any other antimyeloma 
treatment. For participant discontinuing treatment in the PACT phase, no end of treatment visit is required. 
4. 
Screening ocular examination will be performed by an ophthalmologist within 21 days prior to the first dosing (see Section 8.2.2. for the list of screening 
ophthalmic exam procedures).  
5. 
C1D1 ocular exam does not need to be repeated if within 21 days of screening exam.  On-study ophthalmic exams will be performed by an ophthalmologist 
every 3 weeks prior to dosing, up to 6th dose of GSK2857916.  At the time of the 6th dose of GSK2857916, if there are significant ophthalmic exam findings, 
participant’s symptoms or vision changes, the frequency of ophthalmic exams may be decreased to every 3 months until EOT.  If a participant subsequently 
develops vision changes or other ocular symptoms, the participant should be promptly evaluated by an ophthalmologist.  In case of persistent ophthalmic exam 
findings, newly developed ocular symptoms or vision changes, the participants will have further ophthalmic exams, at least every cycle until resolution (to 
Grade 1 or baseline) or more frequently as clinically indicated by an ophthalmologist.  See Section 8.2.2. for the list of ophthalmic exam procedures.  Intraocular 
pressure must be monitored if steroid eye drops are used continuously more than 7 days. 
6. 
Ophthalmic exam at the EOT to be performed by an ophthalmologist.  Participants with corneal signs per the GSK scale at the EOT Visit will continue to be 
followed at 3 weeks (7 days) after the EOT visit and then every 6 weeks (7 days) for up to 12 months, or until full resolution of findings defined as a return to 
participant’s baseline or deemed clinically stable by an ophthalmologist, whichever comes first.  See Section 8.2.2 for the list of ophthalmic exam procedures. 
7. 
Hematology and vital signs (as clinically indicated) must be repeated prior to each dose of bortezomib. 
8. 
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes (5 minutes), EOI (5 minutes), and 
1 hour post EOI (5 minutes).  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI).  The Sentinel Participant 
must be observed for at least 24 hours post EOI.  On days where vital sign timepoints align with PK sampling timepoints, vital signs should be assessed prior to 
PK samples being drawn. 
9. 
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on C1D1.  Refer to Table 32 for comprehensive list of laboratory tests. 


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10. eGFR is to be calculated via modified diet in renal disease (MDRD) calculation. 
11. Albumin/creatinine ratios (spot urine from first void) at screening, C1, and every cycle thereafter. 
12. Troponin I or T and B-type natriuretic peptide (BNP) will be measured at the local laboratory, or by central laboratory if not available locally.  If cardiac workup 
is required due to safety concerns during the study, troponin I or T and BNP should be measured as clinically indicated. 
13. Baseline disease assessments completed within 21 days of C1D1 do not need to be repeated on C1D1. 
14. Only in patients with IgD/IgE myeloma. 
15. Perform only on women of childbearing potential (WOCBP), see Appendix 3 for definition.  A serum pregnancy test must be performed at screening; if the test 
is completed within 72 hours prior to the first dose of GSK2857916, this assessment does not have to be repeated on C1D1.  For questionable cases, 
follicle-stimulating hormone (FSH) and estradiol (as needed in WOCBP) should be performed at local lab to determine childbearing potential.  WOCBP must 
have a negative highly sensitive serum pregnancy test within 72 hours of dosing on C1D1.  Subsequent pregnancy tests on dosing days may be either serum or 
urine.  Final pregnancy test (serum or urine) must be performed in WOCBP at the EOT Visit.  Follow up pregnancy assessment by telephone (for WOCBP only) 
should be performed 4 months after the last dose of GSK2857916 or 7 months after the last dose of bortezomib, whichever is longest. 
16. Skeletal Survey: Imaging of bones for lytic lesions by a method aligned with the institutional guidance (X-ray, CT, or MRI).  Skeletal survey results within 
30 days prior to C1D1 are acceptable. 
17. On dosing days, ECG to be performed in singlet at predose (within 30 minutes prior to SOI). 
18. Echocardiography for left ventricular ejection fraction (LVEF) performed within 35 days prior to first dose is acceptable as screening value. 
19. Imaging is only required for participants with extramedullary disease (CT, MRI, or PET/CT can be applied per local guidance).  Screening assessment may be 
performed up to 30 days prior to C1D1.  The same modality should be used throughout the study (i.e., if CT scan was used as baseline, participant needs to be 
followed by CT scans).  Plasmacytoma measurements should be taken from the CT portion of the PET/CT, or MRI scans, or dedicated CT scans where 
applicable.  For participants with skin only involvement, skin lesions should be measured with a ruler.  Measurement of tumor size will be determined by the 
sum of the products of the maximal perpendicular diameters of measured lesions (SPD). 
20. In participants with extramedullary plasmacytoma, if the last radiographic assessment occurred ≥8 weeks prior to the participant’s withdrawal from study 
treatment, and progressive disease has NOT been documented, –a new assessment for extramedullary disease should be obtained at the EOT. 
21. FISH testing at least for: t(4;14), t(14;16), 17p13del.  FISH results from samples taken within 60 days prior to first dose are acceptable. 
22. Archival tissue from up to 60 days prior to study is acceptable. 
24. Informed consent for optional genetics research should be obtained before collecting a sample.  The sample will be collected between the first opportunity after 
a participant has met all eligibility requirements and the EOT Visit. 
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25. Study treatment administration ±3 day window only. 
26. If a bortezomib dose is delayed, subsequent doses should be adjusted to account for delay as all bortezomib doses must be at least 72 hours apart.  Doses that 
need to be withheld are skipped and will not be made up later in the cycle.  Individual doses within a cycle have a ±1-day window. 
27. Dexamethasone 20 mg orally on Days 1, 2, 4, 5, 8, 9, 11, and 12 of every 21-day cycle.  For participants with contraindications or intolerance to this dose, refer 
to Section 6.7 for instructions on dose modification guidelines.  On days where bortezomib administration coincides with administration of GSK2857916, 
dexamethasone should be administered orally 1 to 3 hours prior to the infusion of GSK2857916.  The starting dose of dexamethasone can be reduced to 10 mg 
in C1 to C8 for participants who are >75 years of age, for participants who have a body mass index (the weight in kilograms divided by the square of the height 
in meters) of less than 18.5, or for participants who had previous unacceptable side effects associated with glucocorticoid therapy.  Participant diaries will be 
used to keep a record of self-administered oral study treatment(s) at home. 
28. Any SAEs assessed as related to study participation or related to a GSK product will be recorded from the time a participant consent through any follow up.  
AEs and SAEs will be collected throughout the study until 70 days after the last dose of study treatment regardless of initiation of new anti-myeloma therapy.  
Concomitant medications administered after the EOT should only be recorded for SAEs/AESIs. 
29. New anticancer therapy will be recorded through any follow up. 


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Table 3 
Schedule of Activities for Part 2 Arm B (GSK2857916 in Combination with Pomalidomide plus Dexamethasone)  
Time and Time Table (Cycle=28 days) 
Study Assessment1 
Screen2 
C1 
C2 
C3 to CX 
End of 
Treatment 
Visit3 
Follow-up 
Visit 
D1 
D8, D15, D22 
D1 
D8, D15, 
D22 
 
D1 
D15 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Baseline Demographics 
X 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Physical Examination 
X 
X 
 
X 
 
X 
 
X 
 
Ocular Examination 
X4 
 
 
X5 
 
X5 
 
X6 
X6 
ECOG Performance Status 
X 
X 
 
X 
 
X 
 
X 
 
Vital Signs (BP, HR, Body 
Temperature) 
X 
X7 
 
X7 
 
X7 
 
X 
 
Weight and Height 
X 
Weight Only 
 
Weight Only 
 
Weight Only 
 
Weight Only 
 
Hematology 
X 
X8 
X 
X 
X 
X 
X 
X 
 
Clinical chemistry 
X 
X8 
X 
X 
X 
X 
X 
X 
 
Urine Dipstick 
X 
X8 
 
X 
 
X 
 
X 
 
eGFR9 
X 
X 
 
X 
 
X 
 
X 
 
Spot urine for Albumin 
/creatinine ratio10 
X 
X 
 
X 
 
X 
 
X 
 
HBV/HCV tests 
X 
 
 
 
 
 
 
 
 
Troponin11, BNP11 
X 
 
 
 
 
 
 
 
 
UPEP and urine Immunofixation 
X 
 
 
X 
 
X 
 
X 
 


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Time and Time Table (Cycle=28 days) 
Study Assessment1 
Screen2 
C1 
C2 
C3 to CX 
End of 
Treatment 
Visit3 
Follow-up 
Visit 
D1 
D8, D15, D22 
D1 
D8, D15, 
D22 
 
D1 
D15 
SPEP and serum 
Immunofixation, Serum M-
protein Calculation 
X 
 
 
X 
 
X 
 
X 
 
Kappa, lambda FLC, FLC Ratio 
X 
 
 
X 
 
X 
 
X 
 
24 hour urine protein  
X 
 
 
X 
 
X 
 
X 
 
Calcium corrected for albumin 
(serum) 
X 
 
 
X 
 
X 
 
X 
 
IgG, IgM, IgA 
X 
 
 
X 
 
X 
 
X 
 
IgD/E12 
X 
 
 
X 
 
X 
 
X 
 
CRP 
X 
 
 
X 
 
X 
 
X 
 
Beta2 microglobulin 
X 
 
 
X 
 
X 
 
 
 
Pregnancy Test13 
X 
X 
X 
X 
 
X 
 
X 
X 
Skeletal survey14 
X 
As clinically indicated 
 
Chest X-ray imaging 
X 
As clinically indicated 
X 
 
12-lead ECG15 
X 
X 
 
 
 
 
 
X 
 
LVEF (ECHO)16 
X 
 
 
 
 
 
 
X 
 
Extramedullary plasmacytoma 
Imaging17 
X 
 
 
 
 
C5, C9, C13, 
And later only 
if clinically 
indicated 
 
X18 
 


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Time and Time Table (Cycle=28 days) 
Study Assessment1 
Screen2 
C1 
C2 
C3 to CX 
End of 
Treatment 
Visit3 
Follow-up 
Visit 
D1 
D8, D15, D22 
D1 
D8, D15, 
D22 
 
D1 
D15 
FISH testing19 
X 
 
 
 
 
 
 
 
 
BM aspirate/biopsy for disease 
assessment 
X20 
 
 
 
 
At the time of 
CR or at time 
of suspected 
Progressive 
disease (only 
if not evident 
otherwise) 
 
Only if CR has 
been achieved 
by this visit, or 
suspected 
Progressive 
disease not 
evident 
otherwise 
 
Serum (anti-drug-antibodies)21 
 
X (See 
Section 8.9) 
 
X (See 
Section 8.9) 
 
X (See 
Section 8.9) 
 
X 
 
Pharmacokinetic blood sampling 
for GSK285791621 
 
X (See Table 35) 
 
Genetics Sample22 
X 
 
Premedication if needed 
 
X 
 
X 
 
X 
 
 
 
GSK2857916 administration23 
 
X 
 
X 
 
X 
 
 
 
Pomalidomide administration24 
 
D1-D21 of each 28-day cycle 
 
 
 
Dexamethasone administration25 
 
D1, D8, D15 and D22 of each 28-day cycle 
 
 
 
Preservative-free Artificial Tears 
 
Administered in each eye at least 4-8 times daily beginning on C1D1 until EOT.  In the event of ocular symptoms 
(i.e., dry eyes), the use of artificial tears may be increased up to every 2 hours, as needed. 
 
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Time and Time Table (Cycle=28 days) 
Study Assessment1 
Screen2 
C1 
C2 
C3 to CX 
End of 
Treatment 
Visit3 
Follow-up 
Visit 
D1 
D8, D15, D22 
D1 
D8, D15, 
D22 
 
D1 
D15 
Cooling Eye Masks (optional) 
 
On GSK2857916 dosing day, may apply cooling eye masks as long as tolerated from start of infusion and up to 
4 hours 
 
Adverse Events26 
X 
Continuous 
X 
Concomitant Medications26 
X 
Continuous 
X 
New anti-myeloma Therapy27 
 
 
 
 
 
 
 
 
X 
1. 
Assessments scheduled on days of dosing should be done prior to drug administration, unless otherwise specified.  All other assessments can be performed 
within ±3 days of scheduled occurrence unless otherwise specified.  D8, D15, and D22 assessments can be performed within ±1 day of scheduled occurrence.  
2. 
All Screening assessments must be performed within 21 days prior to first dose unless otherwise specified.  Informed Consent must be signed before any 
study-specific assessments are performed.  
3. 
The End of Treatment (EOT) Visit will occur within 30 days (±3 days) after the last dose of any study medication or before the initiation of any other 
antimyeloma treatment. For participant discontinuing treatment in the PACT phase, no end of treatment visit is required. 
4. 
Screening ocular examination will be performed by an ophthalmologist within 21 days prior to the first dosing (see Section 8.2.2. for the list of screening 
ophthalmic exam procedures).   
5. 
On-study ophthalmic exams to be performed by an ophthalmologist every 4 weeks prior to dosing, up to the 6th dose of GSK2857916.  At time of the 6th dose of 
GSK2857916, if there are no significant ophthalmic exam findings, participant’s symptoms or vision changes, the frequency of ophthalmic exams may be 
decreased to every 3 months until EOT.  If a participant subsequently develops vision changes or other ocular symptoms, the participant should be promptly 
evaluated by an ophthalmologist.  In case of persistent ophthalmic exam findings, newly developed ocular symptoms or vision changes, the participants will 
have further ophthalmic exams, at least every cycle until resolution (to Grade 1 or baseline) or more frequently as clinically indicated by an ophthalmologist.  
See Section 8.2.2. for the list of ophthalmic exam procedures.  Intraocular pressure must be monitored if steroid eye drops are used continuously more than 
7 days. 
6. 
Ophthalmic exam at the EOT to be performed by an ophthalmologist.  Participants with corneal signs per the GSK scale at the EOT Visit will continue to be 
followed at 3 weeks (7 days) after the EOT visit and then every 6 weeks (7 days) for up to 12 months, or until full resolution of findings defined as a return to 
participant’s baseline or deemed clinically stable by an ophthalmologist, whichever comes first.  See Section 8.2.2 for the list of ophthalmic exam procedures. 


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7. 
On initial (first infusion) dosing day, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI), +10 minutes (5 minutes), EOI (5 minutes), and 
1 hour post EOI (5 minutes).  On subsequent dosing days, vital signs must be assessed at pre-dose (within 30 minutes prior to SOI).  The Sentinel Participant 
must be observed for at least 24 hours post EOI.  On days where vital sign timepoints align with PK sampling timepoints, vital signs should be assessed prior to 
PK samples being drawn. 
8. 
If completed within 72 hrs prior to the first dose, this assessment need not be repeated on C1D1.  Refer to Table 32 for comprehensive list of laboratory tests. 
9. 
eGFR is to be calculated via modified diet in renal disease (MDRD) calculation. 
10. Albumin/creatinine ratios (spot urine from first void) at screening, C1, and every cycle thereafter. 
11. Troponin I or T and B-type natriuretic peptide (BNP) will be measured at the local laboratory, or by central laboratory if not available locally.  If cardiac workup 
is required due to safety concerns during the study, troponin I or T and BNP should be measured as clinically indicated. 
12. Only in patients with IgD/IgE myeloma. 
13. Perform only in women of childbearing potential (WOCBP), see Appendix 3 for definition.  A serum pregnancy test must be performed at screening.  Two 
negative serum pregnancy tests must be obtained prior to initiating treatment; the first test should be performed within 10 to 14 days of C1D1, but the second 
must be performed within 24 hours of C1D1.  After the first dose, pregnancy test will be done weekly during the first month, then every cycle thereafter (or 
every 2 weeks in females with irregular menstrual cycles).  Subsequent pregnancy test on dosing days may be either serum or urine test.  Each pregnancy test 
must be performed within 24 hours prior to dosing.  Final pregnancy test (serum or urine) must be performed in WOCBP at the EOT visit and at 2 weeks (in 
case of irregular menses) and 4 weeks following treatment discontinuation.  Follow up pregnancy assessment by telephone (for WOCBP only) should be 
performed 4 months after the last dose of GSK2857916 or 4 weeks after the last dose of pomalidomide, whichever is longest. 
14. Skeletal Survey: Imaging of bones for lytic lesions by a method aligned with the institutional guidance (X-ray, CT, or MRI).  Skeletal survey results within 
30 days prior to C1D1 are acceptable. 
15. On dosing days, ECG to be performed in singlet at predose (within 30 minutes prior to SOI). 
16. Echocardiography for left ventricular ejection fraction (LVEF) performed within 35 days prior to first dose is acceptable as screening value. 
17. Imaging is only required for participants with extramedullary disease (CT, MRI, or PET/CT can be applied per local guidance).  Screening assessment may be 
performed up to 30 days prior to C1D1.  The same modality should be used throughout the study (i.e., if CT scan was used as baseline, participant needs to be 
followed by CT scans).  Plasmacytoma measurements should be taken from the CT portion of the PET/CT, or MRI scans, or dedicated CT scans where 
applicable.  For participants with skin only involvement, skin lesions should be measured with a ruler. Measurement of tumor size will be determined by the 
Sum of the Products of the maximal perpendicular diameters of measured lesions (SPD). 
18. In participants with extramedullary plasmacytoma, if the last radiographic assessment occurred ≥8 weeks prior to the participant’s withdrawal from study 
treatment, and progressive disease has NOT been documented, –a new assessment for extramedullary disease should be obtained at the EOT. 
19. FISH testing at least for: t(4;14), t(14;16), 17p13del.  FISH results from samples taken within 60 days prior to first dose are acceptable. 
20. Archival tissue from up to 60 days prior to study is acceptable. 


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22. Informed consent for optional genetics research should be obtained before collecting a sample.  The sample will be collected between the first opportunity after 
a participant has met all eligibility requirements and the EOT Visit. 
23. Study treatment administration ±3 day window only. 
24. On days where only pomalidomide and dexamethasone are taken at home, they should be taken in the morning approximately at the same time each day.  
Platelet count must be ≥50,000/mL to initiate new cycle.  Refer to Section 6.7 for dose modification guidelines and instructions on dose delays.  Participant 
diaries will be used to keep a record of self-administered oral study treatment(s) at home. 
25. Dexamethasone 40 mg orally on D1, D8, D15, and D22 of every 28-day cycle.  For participants who are >75 years or have comorbidities or are intolerant to 
40 mg, the dose of dexamethasone can be reduced to 20 mg.  Refer to Section 6.7 for dose modification guidelines and instructions on dose delays.  On days 
where only pomalidomide and dexamethasone are taken at home, they should be taken in the morning approximately at the same time each day.  On 
GSK2857916 dosing days, dexamethasone should be administered 1 to 3 hours prior to the first administration of GSK2857916.  Participant diaries will be used 
to keep a record of self-administered oral study treatment(s) at home. 
26. Any SAEs assessed as related to study participation or related to a GSK product will be recorded from the time a participant consent through any follow up.  
AEs and SAEs will be collected throughout the study until 70 days after the last dose of study treatment regardless of initiation of new anti-myeloma therapy.  
Concomitant medications administered after the EOT should only be recorded for SAEs/AESIs. 
27. New anticancer therapy will be recorded through any follow up. 
 
Table 4 
Hepatitis B (HBV) SoA – additional procedures  
Note: the procedures listed in this table apply ONLY to participants in screening and who have been enrolled and who have a history of 
Hepatitis B; all procedures must be done as needed in addition to the required procedures for all participants detailed in Table 2 and 
Table 3.  
HBV Study Assessments 
During Screening / 
Prior to starting 
treatment 
During Treatment 
EOT  
Notes 
HBV-DNA testing 
X1 
X1 
X1 
1. 
HBV-DNA testing prior to the start of GSK2857916 and subsequently 
every 3 months, or if LFT elevations requiring increased monitoring or 
stopping criteria occurs, or for any clinical suspicion of hepatitis 
reactivation.   
 
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2. 
INTRODUCTION  
Multiple myeloma (MM) is a malignancy of the plasma cells that is characterized by 
monoclonal protein in blood and urine, and has multiple symptoms such as 
haematopoietic disorder, renal disorder, bone pains. 
Multiple myeloma is an incurable malignancy and accounts for 1.8% of all new cancers 
and 13% of all hematologic malignancies [SEER CSR, 2018].  Worldwide, 
approximately 103,000 new cases are diagnosed annually [Cowan, 2018] and in the 
United States (US), 32,110 new cases and 12,960 deaths are estimated to occur in 2019 
[Siegel, 2019].  Incident cases from 1990 to 2016 increased by 126% globally [Cowan, 
2016].  In Japan, the number of patients with MM was 8,200, and that of deaths was 
4,200 in 2017 [NCCN, 2017].  Due to aging of society, incidence of MM has increased 
recently [Ozaki, 2015]. 
There have been significant advances in treatment for MM, including novel therapies like 
second and third-generation proteasome inhibitors, immunomodulatory drugs (IMiDs), 
and recent addition of monoclonal antibodies (mAbs). Those advances have contributed 
to incremental gains in progression free survival (PFS) and overall survival (OS).  
Despite the recent advances in therapy, MM remains an incurable disease, and novel 
approaches that induce deep and durable tumor regression with little cross-resistance with 
existing drugs are always needed to expand the therapeutic options against MM. 
2.1. 
Study Rationale  
Over the past two decades, the median survival of patients with MM has significantly 
improved, from 3 to 4 years to approximately 7 to 8 years, mainly due to the application 
of high-dose conventional therapy with autologous stem-cell transplantation 
(HDT-ASCT) as a routine procedure for transplant-eligible MM patients; significant 
improvements in supportive care strategies; and the introduction and wide-spread use of 
the IMiDs thalidomide and lenalidomide and the proteasome inhibitor, bortezomib 
[Nijhof , 2018].  Similarly, IMiDs and proteasome inhibitors are the novel agents 
approved for treatment of relapsed/refractory multiple myeloma (RRMM) in Japan. The 
survival outcome has significantly improved after the introduction of these novel agents 
[Ozaki, 2015].  In Japan, the regiments with bortezomib, lenalidomide or thalidomide as 
salvage therapy, or ASCT are recommended for RRMM [Japanese Society of 
Hematology, 2013].  These novel agents nowadays represent the backbone of many 
current standard-of-care therapies for MM patients, both at diagnosis and in the relapse 
setting. 
Daratumumab [DARZALEX, 2017], is a human immunoglobulin G (IgG) 1 kappa 
monoclonal antibody that targets CD38, a cell surface protein that is overexpressed on 
MM cells.  The drug was granted accelerated approval as monotherapy for the treatment 
of RRMM in the US in November 2015 [Afifi, 2016] on the basis of the results from a 
Phase II monotherapy study (n=106) which reported 29.2% overall response rate (ORR) 
and median PFS (mPFS) 3.7 months in patients with RRMM.  Daratumumab received 
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While the data with daratumumab indicate that further prolongation of PFS can be 
achieved, it is also increasingly recognized that patients continue to relapse after 
treatment with daratumumab, and will need additional treatment options to control the 
disease. 
GSK2857916 is a first in class, antibody-dependent cell-mediated cytotoxicity (ADCC) 
enhanced, humanized IgG1 antibody-drug conjugate (ADC) that binds specifically to 
B-cell maturation antigen (BCMA), a target restricted to B cells at later stages of 
differentiation and expressed on tumor cells of all patients with MM [Tai, 2015; 
Tai, 2006].  The normal function of BCMA is to promote cell survival by transduction of 
signals from two known ligands (BAFF[BlyS] and a proliferation-inducing ligand 
[APRIL]).  The expression is restricted to B cells at later stages of differentiation, with 
expression on germinal center B cells in tonsil, blood plasma blasts and long lived plasma 
cells [Darce, 2007].  The expression levels in MM vary from patient to patient, but 
GlaxoSmithKline (GSK) studies demonstrate that all patients tested express detectable 
levels of BCMA protein on their tumor cells. 
GSK2857916 has shown strong single-agent activity in 2 clinical studies conducted in 
heavily pre-treated participants with RRMM [Trudel, 2018; Trudel, 2019; Lonial, 2020]. 
Among the 35 participants in BMA117159 study, receiving GSK2857916 at the 
recommended phase II dose (RP2D) of 3.4 mg/kg intravenously (IV), once every 3 weeks 
(Q3W), the following results were observed as of 31 August 2018:  
 
ORR of 60% [95% confidence interval (CI): 42.1, 76.1] 
 
mPFS was 12.0 months [95% CI: 3.1, not estimable (NE)]. 
 
The ORR in 32 participants to both IMiDs and proteasome inhibitors was 56% 
(95% CI: 37.7, 73.6), and the mPFS in this subgroup was 7.9 months (95% CI: 
2.3, NE). 
 
Overall, GSK2857916 was well tolerated and adverse events (AEs) were 
manageable. 
This data supports testing of GSK2857916 as a monotherapy in Japanese participants 
with RRMM. 
In addition, given the strong single-agent activity of GSK2857916, the combination 
therapy of GSK2857916 with standard of care (SoC) agents is an attractive option to 
explore for patients with RRMM.  Based on the mechanism of action of GSK2857916, 
the combination with SoC therapies (bortezomib and dexamethasone [Bor/Dex] or 
pomalidomide and dexamethasone [Pom/Dex]) is expected to result in additive, or 
potentially synergistic effects which could potentially translate into a deep and 
long-lasting response over what has been achieved with available agents. 
The ongoing Phase I/II open-label, dose escalation and expansion study 207497 is 
evaluating the safety and clinical activity of GSK2857916 when given in combination 
with Bor/Dex in patients with RRMM who have received at least 1 prior line of therapy.  
Preliminary data from this study indicate that the combination of GSK2857916 at 
2.5 mg/kg dose with Bor/Dex is safe and tolerable without dose limiting toxicities (DLT) 


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and is showing early evidence of activity, given the prior and ongoing experience (from 
first time in human [FTIH] study BMA117159 and Phase II 205678 study) of single 
agent activity for this dose (2.5 mg/kg) of GSK2857916. 
GSK2857916 at multiple dose levels in combination with Pom/Dex once every 4 weeks 
(Q4W) is being evaluated for safety and efficacy in patients with RRMM in an ongoing 
Phase I/II study conducted by the MCRN (MCRN 007 or study 209418).  As of 
01 February 2020, 11 participants have received GSK2857916 at 1.92 mg/kg dose, and 
7 participants at 2.5 mg/kg dose in combination with Pom/Dex Q4W.  Preliminary data 
showed that the GSK2857916/Pom/Dex combination at both dose levels has resulted in 
early signs of clinical activity, and an acceptable safety profile, consistent with the known 
safety profile of the individual components, GSK2857916 and Pom/Dex. 
These data support testing GSK2857916 when administered in combination with 
approved regimens of either Bor/Dex (Arm A) or Pom/Dex (Arm B) in Japanese 
participants with RRMM in Part 2. 
2.2. 
Background – BCMA and Multiple Myeloma  
B-cell maturation antigen (BCMA also referred to as TNFRSF17 or CD269) is a member 
of the tumor necrosis factor (TNF) receptor superfamily and regulates a variety of 
cellular functions.  BCMA is expressed in mature B lymphocytes and binds to two TNF 
family ligands BAFF (B-cell-activating factor belonging to the TNF family) and APRIL 
(a proliferation-inducing ligand) which promotes B-cell survival and proliferation.  Mice 
deficient for BCMA are viable, have normal B-cell development, and exhibit normal 
humoral responses [Belnoue, 2008; Varfolomeev, 2004; Jiang, 2011].  BCMA is 
expressed on malignant plasma cells in all MM patients [Tai, 2015; Tai, 2006].  The 
restricted expression profile of BCMA in normal tissue, combined with its up-regulation 
and recognized survival function in MM [Tai, 2006; Sanchez, 2012; Novak, 2004] makes 
BCMA an attractive target for a therapeutic antibody with direct cell killing activity and 
with minimal off target effects [Tai, 2015].  BCMA has been validated as a therapeutic 
target in MM [Tai, 2015].  The BMA117159 study was the FTIH study demonstrating 
single-agent activity of GSK2857916 in heavily pre-treated MM participants.  
2.3. 
Antibody-Drug Conjugate GSK2857916  
GSK2857916 binds to BCMA and kills MM cells via a multi-modal mechanism 
including delivery of cytotoxic, monomethyl auristatin-F (MMAF) (cysteine 
maleimidocaproyl MMAF [cys-mcMMAF]) to BCMA-expressing MM cells, thereby 
inducing apoptosis, enhancing ADCC and antibody-dependent cellular phagocytosis 
(ADCP), and inducing immunogenic cell death (Figure 1) [Tai, 2014; Montes De Oca, 
2019].  Exposure of dendritic cells to tumor cells undergoing immunogenic cell death is 
expected to result in an antigen-specific T-cell response, enhancing the immunogenic 
response against MM. 


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Figure 1 
GSK2857916 Mechanism of Action  
 
ADCC/ADCP=antibody-dependent cell-mediated cytotoxicity/antibody-dependent cellular phagocytosis 
2.3.1. 
Human Experience with GSK2857916  
2.3.1.1. 
Studies with GSK2857916 Monotherapy  
Single-agent GSK2857916 has demonstrated to have a strong single-agent activity with a 
well-defined manageable safety profile in heavily pre-treated participants with RRMM 
(Q3W schedule vis IV administration).  Safety data for single-agent GSK2857916 were 
pooled (data as of 20 September 2019) for study 205678 (DREAMM-2; NCT03525678) 
and supportive FTIH study BMA117159 (DREAMM-1; NCT02064387), by treatment 
cohorts of 2.5 mg/kg and 3.4 mg/kg. 
FTIH study BMA117159/DREAMM-1 
In the FTIH study BMA117159, which consisted of a dose escalation phase (Part 1, 
n=38) and a dose expansion phase (Part 2, n=35), as of the primary analysis cut-off date 
of 31 August 2018, a total of 73 participants with RRMM received at least 1 dose of 
GSK2857916 [GSK2857916 IB; Trudel, 2019]. 
As of the efficacy cut-off date of 31 August 2018, a total of 35 participants were treated 
at the 3.4 mg/kg dose in Part 2 of the DREAMM-1 study.  Participants were heavily 
pre-treated: 57% of participants had 5 or more prior lines of therapy.  The ORR was 60% 
(95% CI: 42.1, 76.1): comprised of partial response (PR), 6%; very good partial response 
(VGPR), 40%; complete response (CR), 9%; and stringent CR (sCR), 6%.  The median 
duration of response (DoR) was 14.3 months (95% CI: 10.6, not reached [NR]).  The 
mPFS in this population was 12.0 months (95% CI: 3.1, NE).  For participants refractory 
to both IMiDs and proteasome inhibitors (n=32/35), the confirmed ORR was 56% (95% 
CI: 37.7, 73.6) and mPFS was 7.9 months (95% CI: 2.3, NE) [Trudel, 2019]. 


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Phase II study 205678/DREAMM-2 
The ongoing Phase II study 205678/DREAMM-2 is evaluating these two IV single agent 
doses (2.5 and 3.4 mg/kg) administered Q3W until disease progression in participants 
who have failed at least 3 prior lines of anti-myeloma therapy, including an anti-CD38 
antibody, and who are refractory to an IMiD and a proteasome inhibitor.  A total of 
194 participants received frozen drug product in the main cohort and 24 participants 
received 3.4 mg/kg lyophilized drug product.  The study met its primary endpoint for 
ORR in both the 2.5 mg/kg and 3.4 mg/kg treatments, and the benefit of GSK2857916 
was supported by the secondary endpoints.  Primary analysis data from this study 
indicated no new safety signals, and the profile of AEs was similar to the experience in 
the DREAMM-1 study for both arms.  Both dose levels, 2.5 and 3.4 mg/kg, were shown 
to have a positive benefit/risk profile [Lonial, 2020]. 
As of the cut-off date of 31 January 2020, the ORR in the 2.5 mg/kg treatment was 31% 
(97.5% CI: 21.7, 43.6) and in the 3.4 mg/kg treatment 35% (97.5% CI: 24.8, 47.0).  The 
median DoR was 11.0 months (95% CI: 4.2, NR) at 2.5 mg/kg and 6.2 months (95% CI: 
4.8, NR) at 3.4 mg/kg.  The mPFS in this population was 2.8 months (95% CI: 1.6, 3.6) 
and 3.9 months (95% CI: 2.0, 5.8), respectively and the median OS was 13.7 months 
(95% CI: 9.9, NR) at 2.5 mg/kg and 13.8 months (95% CI: 10.0, NR) at 3.4 mg/kg.  
Positive clinical activity was also demonstrated at the 3.4 mg/kg lyophilised dose (ORR 
52% [97.5% CI: 28.9, 74.5]). 
2.3.1.1.1. Safety  
Single-agent GSK2857916 was demonstrated to have a manageable safety profile in 
heavily pre-treated participants with RRMM.  Safety data for single-agent GSK2857916 
were pooled (data as of 20 September 2019) for DREAMM-2 study and supportive FTIH 
study DREAMM-1 by treatment cohorts of 2.5 mg/kg and 3.4 mg/kg. 
The most common AEs in both treatment cohorts were keratopathy (corneal epithelium 
changes observed on ophthalmic examination), thrombocytopenia and anemia.  The 
incidence of AEs, including Grade 3/4 AEs was comparable between GSK2857916 
2.5 mg/kg and 3.4 mg/kg cohorts.  AEs leading to dose delays, and reductions were less 
frequent in 2.5 mg/kg cohort, 51% and 32% compared with the 3.4 mg/kg cohort, 67% 
and 52%, respectively. AEs leading to permanent treatment discontinuation occurred in 
10% and 11% of participants in the 2.5 and 3.4 mg/kg cohorts, respectively. More 
participants in the 3.4 mg/kg cohort experienced serious adverse events (SAEs) (50%) 
and fatal SAEs (6%) compared with the 2.5 mg/kg cohort (41% and 3%, respectively). 
Single-agent GSK2857916 2.5 mg/kg was selected as the recommended dose based on 
comparable efficacy with a more favorable safety profile (i.e., lower incidence of 
thrombocytopenia and neutropenia and less frequent dose delays or reductions) compared 
with the 3.4 mg/kg dose. 
Adverse Events of Special Interest 
Adverse events of special interest (AESIs) for GSK2857916 are corneal events, 
thrombocytopenia and infusion-related reactions (IRRs), and are described below. 


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Corneal Events 
Corneal events, reported in most cases as keratopathy, blurred vision and dry eye events 
are the most frequently reported AEs with GSK2857916. 
In DREAMM-2 (data as of 31 January 2020), events in the Eye disorders system organ 
class occurred in 78% of participants treated with GSK2857916 2.5 mg/kg.  The most 
common ocular AEs were keratopathy (71%, changes in corneal epithelium identified on 
eye exam, with or without symptoms), blurred vision (22%), and dry eye (13%).  
Decreased vision defined as Snellen score worse than 20/50 in the better seeing eye was 
reported in 18% of participants receiving GSK2857916 2.5 mg/kg.  Severe vision loss 
defined as 20/200 or worse in the better seeing eye was reported in 1% of participants 
receiving GSK2857916 2.5 mg/kg. 
The median time to onset of Grade 2 or above corneal findings (best corrected visual 
acuity or corneal examination) was 36 days (range: 19 to 143 days) in participants 
receiving GSK2857916 2.5 mg/kg.  The median time to resolution of these corneal 
findings was 91 days (range: 21 to 201 days). 
Participants with history of dry eye were more prone to develop corneal examination 
findings.  Therefore, active management of dry eye symptoms prior to and during 
treatment is recommended (i.e., administration of preservative-free artificial tears). 
The ocular sub-study of DREAMM-2 provided no evidence that corticosteroid eye drops 
are beneficial in preventing or mitigating corneal events. 
Thrombocytopenia 
In DREAMM-2 (data as of 31 January 2020), thrombocytopenic events 
(thrombocytopenia and platelet count decreased) occurred in 38% participants treated 
with GSK2857916 2.5 mg/kg; severity ranging between Grade 1 and 4.  The incidence of 
Grade 3 bleeding events was low (2%), with no Grade 4 or 5 events reported in 
participants treated with GSK2857916 2.5 mg/kg. 
Most participants had a decrease from baseline in their platelet counts during the study.  
In general, participants who initiated treatment with lower platelet numbers tended to 
continue to have thrombocytopenia while on treatment with GSK2857916. 
Infusion-related reactions 
IRRs are expected for biologic agents.  In DREAMM-2 (data as of 31 January 2020), 
IRRs occurred in 21% of participants in the GSK2857916 2.5 mg/kg, which were 
Grade 1 - 3 in severity.  Most IRRs occurred with the first infusion and few participants 
experienced IRRs with subsequent infusions. 
Although not protocol-mandated, pre-medications for IRR prophylaxis (including 
paracetamol, antihistamines, and steroids) were administered to 26% - 27% of 
participants.  One participant (2.5 mg/kg cohort) discontinued treatment due to IRRs 
(Grade 3 IRRs at first and second infusion). 


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2.3.1.2. 
Combination Studies of GSK2857916  
GSK2857916 in Combination with Lenalidomide/Dexamethasone or in Combination 
with Bortezomib/Dexamethasone (Study 207497) 
Study 207497 (NCT03544281, DREAMM 6) is an ongoing Phase I/II, open-label, dose 
escalation and expansion study of GSK2857916 in combination with 2 SoC regimens; 
lenalidomide/dexamethasone (Arm A) in a 28-day cycle, or with Bor/Dex (Arm B) in a 
21-day cycle.  Study 207497 will evaluate safety and clinical activity of the combination 
treatments in participants with RRMM after at least 1 prior line of therapy. 
The study consists of 2 parts.  Part 1 is a dose escalation phase to evaluate the safety and 
tolerability of various dose levels and up to 2 dosing schedules of GSK2857916 in 
combination with the above 2 SoC regimens.  Part 2 of the study is intended to further 
evaluate the safety and clinical activity of up to 3 dose levels and up to 2 dosing 
schedules of GSK2857916 with lenamidomide and dexamethasone or Bor/Dex.  In Part 1 
(dose escalation), the starting dose for GSK2857916 in both arms was 2.5 mg/kg.  
Treatment arms are enrolled and analyzed independently.  Based on data from 
15 participants treated at the dose of 2.5 mg/kg Q3W, followed on study for 1 to 
14 cycles (n= 6 participants with a range of 8 to 14 cycles, an average of 11 cycles and a 
median of 12 cycles as of 26 November 2019), this combination dose has been shown to 
have an acceptable safety profile. 
During Part 1 (dose escalation) of the study, no DLTs were reported for the 3 evaluable 
participants at the 2.5 mg/kg Q3W dose of GSK2857916 in combination with Bor/Dex 
(Arm B) and GSK2857916 dose was escalated to 3.4 mg/kg Q3W.  Part 2 (dose 
expansion) of the study is evaluating the safety and preliminary clinical activity of both 
the dose levels (GSK2857916 2.5 and 3.4 mg/kg) and 2 dosing schedules of 
GSK2857916 (administered as a single dose on Day (D) 1 of each cycle, and, 
administered as 2 equal divided dose a week apart on D1 and D8 of each cycle) in 
combination with Bor/Dex.  Preliminary safety data from Study 207497 is broadly 
consistent with the clinical experience reported with GSK2857916 to date and standard 
combination treatments in the RRMM population.  Based on benefit/risk assessment, a 
dose of GSK2857916 at 2.5 mg/kg Q3W has been selected in combination with Bor/Dex 
for patients with RRMM in at least 2-line settings. 
GSK2857916 in Combination with Pomalidomide and Dexamethasone (Study 
209418)  
Study 209418 (or MCRN007) is an ongoing Phase I/II, dose-escalation study conducted 
by the Myeloma Canada Research Network (MCRN) to evaluate the safety and efficacy 
of GSK2857916 given IV Q4W in combination with Pom/Dex in patients with RRMM.  
The study consists of 2 parts: Part 1 is dose-finding and Part 2 is the expansion phase. 
All participants receive multiple dose levels of GSK2857916 administered IV Q4W in 
combination with Pom/Dex in a 28-day treatment cycle.  Pomalidomide is administered 
at 4 mg once daily (QD) on D1 to D21 of a 28-day cycle and dexamethasone at 40 mg 
QD (participants with 75 years of age or younger) or 20 mg QD (participants older than 
75 years of age) on D1, D8, D15, and D22 of each 28-day cycle.  Treatment will be 


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administered until disease progression or unacceptable toxicity.  The Investigator 
Sponsor performed an analysis based on the instream live data for the purpose of an 
abstract submission (cut-off date of 01 February 2020).  A total of 18 participants were 
included in this report, of which 11 participants GSK2857916 at 1.92 mg/kg dose level, 
and 7 participants at 2.5 mg/kg dose level. 
The accumulative treatment cycles were ranged from 1 to 9 cycles in 1.92 mg/kg cohort 
and 3 to 9 cycles in at 2.5 mg/kg cohort.  One participant was non-evaluable for DLT 
assessment in each dose cohort.  Based on the dose escalation criteria, both 1.92 mg/kg 
and 2.5 mg/kg dose levels of GSK2857916 were considered to have cleared the DLT 
evaluation period.  This combination regimen has an acceptable safety profile, consistent 
with the known safety profile of the individual components, GSK2857916 and Pom/Dex.  
The most frequently reported AEs were corneal and haematological toxicities and most 
events resolved (or were resolving) following protocol defined monitoring and dose 
modifications. 
Responses obtained in the 2.5 mg/kg cohort were deep and rapid, with PR or VGPR 
responses achieved within first 2 cycles.  However, in the 2.5 mg/kg dose cohort, all 
7 participants treated at 2.5 mg/kg of GSK2857916 experienced Grade 2 or 3 ocular 
toxicities within 2 cycles of therapy requiring dose interruptions and dose reductions of 
GSK2857916 from 2.5 mg/kg to 1.92 mg/kg Q4W.  Despite these dose modifications, all 
7 participants achieved deep responses (best overall response 6 VGPR and 1 sCR) and 
2 participants experienced disease progression. 
The dose cohort of 1.92 mg/kg Q4W was better tolerated with less frequent dose 
interruptions of GSK2857916.  However, the efficacy observed thus far (4 stable disease 
[SD], 2 PR and 4 VGPR, 2 participants had disease progression) appears inferior than the 
efficacy observed in the dose cohort of 2.5 mg/kg Q4W.  One participant withdrew 
consent in the 1.92 mg/kg dose cohort. 
2.3.1.3. 
Pharmacokinetics and Pharmacodynamics in Human  
The pharmacokinetics (PK) and pharmacodynamics (PD) of GSK2857916 
(antibody-drug conjugate, including complex with 
 total mAb 
(including complex), and cys-mcMMAF were investigated in 291 participants with 
RRMM following IV administration at doses from 0.03 to 4.6 mg/kg Q3W in Study 
BMA117159 (n=73) and at doses of 2.5 or 3.4 mg/kg Q3W in Study 205678 (n=218). 
Maximum observed concentrations (Cmax) of GSK2857916 and total mAb were 
observed at the end of infusion (EOI), while cys-mcMMAF Cmax values were generally 
observed on Day 2. On a molar basis, plasma concentrations of cys-mcMMAF were <1% 
of GSK2857916 concentrations. There was limited accumulation (less than 2-fold) of 
GSK2857916 or cys-mcMMAF during subsequent cycles. 
GSK2857916 PK were described by a linear, two-compartment population model, with 
time-varying decrease in clearance in a population PK analysis.  At Cycle 1 (C1), 
GSK2857916 had a systemic clearance of 0.92 L/day, steady-state volume of distribution 
of 10.8 L, and an elimination half-life of 12 days in participants with RRMM in Study 
CCI


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205678.  Over time, clearance was reduced by 28%, resulting in an elimination half-life 
of 14 days.  The time to 50% change in clearance was approximately 50 days. 
No clinically significant differences in the PK of GSK2857916 or cys-mcMMAF were 
observed based on age (34 to 89 years), sex, race (African American/Black and White), 
body weight (42 to 130 kg), mild or moderate renal impairment (estimated glomerular 
filtration rate [eGFR] ≥ 30 mL/min/1.73m2) or mild hepatic impairment (National Cancer 
Institute [NCI]-organ dysfunction working group classification).  Higher serum levels of 
2-microglobulin, IgG, and 
) and lower levels of albumin are 
associated with more advanced multiple myeloma or a higher multiple myeloma disease 
burden.  Higher baseline IgG and 
 levels, and lower baseline albumin levels were 
associated with higher GSK2857916 clearance leading to lower average and trough 
concentrations of GSK2857916. Higher baseline IgG and 
 levels were associated 
with higher cys-mcMMAF central volume of distribution leading to lower cys-mcMMAF 
Cmax. 
In nonclinical studies, cys-mcMMAF had limited metabolic clearance.  In vitro data 
suggested that GSK2857916 and cys-mcMMAF are unlikely to perpetrate a drug-drug 
interaction or to be a victim of a drug-drug interaction with inhibitors or inducers of 
cytochromes P (CYP) 450.  Cys-mcMMAF was an in vitro substrate of organic anion 
transporting polypeptides (OATP)1B1 and OATP1B3, multidrug resistance associated 
proteins (MRP)1, MRP2, and MRP3, a borderline substrate of bile salt export pump, and 
a possible substrate of P-glycoprotein (P-gp).  Following the administration of 
GSK2857916 to participants with RRMM, only intact cys-mcMMAF was detected in 
pooled human urine, with no evidence of other MMAF-related urinary metabolites. 
The PK of bortezomib and GSK2857916 were evaluated when administered in 
combination with dexamethasone in Study 207497.  Based on preliminary PK data, as 
anticipated, GSK2857916 did not appear to impact the PK of bortezomib. 
Free 
 levels were measured in Study BMA117159 and Study 205678.  All 
participants exhibited reductions in free
 concentration at EOI compared to 
baseline at C1, with a return to near-baseline level by seven days after dosing, reflecting 
binding of GSK2857916 to 
.  Maximum decreases ranged from 2% to 97%, 
which were qualitatively dose-dependent, with larger reductions in free
 at higher 
doses.  
Exposure-response analyses performed for Study 205678 and/or Study BMA117159 
found that ocular safety endpoints were most strongly associated with GSK2857916 
exposure, while efficacy endpoints had a weaker association with GSK2857916 
exposure. Both safety and efficacy endpoints were associated with participant 
characteristics. GSK2857916 trough concentration was associated with probability of 
corneal events and keratopathy and cys-mcMMAF Cmax was associated with probability 
of thrombocytopenia.  Probability of occurrence of dry eye, blurred vision, neutropenia 
and infusion related reaction were not associated with an exposure measure. In addition, 
the results of the analysis of concentration against corrected QT interval (QTc) 
demonstrated that GSK2857916 or cys-mcMMAF did not have a significant effect on 
cardiac repolarization. 
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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Additional information related to GSK2857916 clinical PK, PD, and exposure-response 
relationships can be found in the Investigator’s Brochure (IB) [GSK2857916 IB GSK 
Document Number 2013N175128_09, 2021]. 
2.4. 
Benefit/Risk Assessment  
More detailed information about the known and expected benefits and risks and 
reasonably expected AEs of GSK2857916 may be found in the GSK2857916 IB 
(GlaxoSmithKline Document Number 2013N175128); prescribing information for 
pomalidomide, bortezomib, and dexamethasone can be found in the Study Reference 
Manual (SRM). 
 


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2.4.1. 
Risk Assessment  
Additional information about the known and expected benefits and risks, detailed information of nonclinical and clinical findings 
information regarding warnings, precautions, contraindications, AEs, and other pertinent information on GSK2857916 that may impact 
participant eligibility is provided in the IB [GSK2857916 IB]. 
Risk Assessment and Mitigation Strategy 
Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Potential Overlapping Toxicities for GSK2857916/Bortezomib/Dexamethasone (Part 2 Arm A) and GSK2857916/Pomalidomide/Dexamethasone (Part 2 Arm B) 
Thrombocytopenia 
GSK2857916: GSK2857916 may cause transient 
thrombocytopenia in some participants, which for most cases 
recovered between doses. 
In the pooled safety population of study 205678 which included 
participants treated with GSK2857916 2.5 and 3.4 mg/kg, 
thrombocytopenia was noted in 46% of participants and ranged 
between Grade 1 to 4 in severity. 
Part 2 Arm A 
Bortezomib: Bortezomib is associated with thrombocytopenia that 
follow a cyclical pattern with nadirs occurring following the last dose 
of each cycle and typically recovering prior to initiation of 
subsequent cycle. 
Part 2 Arm B 
Pomalidomide: Pomalidomide is associated with 
thrombocytopenia. 
Routine hematologic monitoring as outlined in the schedule of activities (SoA). 
Supportive therapy per local medical practice (e.g., platelet transfusion). 
Dose modification guidelines are detailed in Section 6.7. 


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Increased Infections 
due to 
Immunosuppression 
or neutropenia 
GSK2857916: In nonclinical studies, GSK2857916 has been 
associated with decrease in immunoglobulins in monkeys, at all 
doses.  An increase in immunoglobulins was seen in rats (rats are 
not an antigen-specific species for GSK2857916). 
Immunosuppression is frequently associated with an increased risk 
of infection.  Serious and non-serious infections have been reported 
in GSK2857916 studies, including respiratory infections, pneumonia 
and sepsis. 
Neutropenic events, including febrile neutropenia have been 
observed with GSK2857916. 
Dexamethasone: Patients who are on corticosteroids are more 
susceptible to infections or exacerbation of latent infections than 
healthy individuals.  Chickenpox and measles can have a more 
serious or even fatal course in pediatric and adult patients on 
corticosteroids. 
Part 2 Arm A 
Bortezomib: Cases of herpes zoster reactivation and infection 
have been reported in patients receiving bortezomib. 
Part 2 Arm B 
Pomalidomide: Neutropenia was reported, rate of Grade 3-4 
neutropenia was 46% and febrile neutropenia was 8%. 
Patients with an active infection excluded. 
Monitoring for infections and immediate treatment of immunosuppression 
according to standard practice. 
Routine monitoring of hematologic panels as outlined in the SoA. 
Supportive therapy per local medical practice (e.g. growth factors). 
Prophylactic antibiotics, per local institutional guidance, in participants with Grade 
3-4 neutropenia. 
Immediate hospitalization of participants with febrile neutropenia. 
Dose modification guidelines are outlined in Section 6.7. 
Participants on bortezomib will receive herpes zoster prophylaxis (e.g., acyclovir 
or other antiviral agent) according to institutional guidelines. 
If exposed to chickenpox, prophylaxis with Varicella-Zoster immune globulin 
(VZIG) may be indicated.  If exposed to measles, prophylaxis with immune 
globulin may be indicated. 


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Other Hematological 
Effects 
GSK2857916:  
Anemia is a common complication in the RRMM population and 
was frequently reported in GSK2857916 clinical program. 
Part 2 Arm A 
Bortezomib: Associated with thrombocytopenia and neutropenia 
that follow a cyclical pattern with nadirs occurring following the last 
dose of each cycle and typically recovering prior to initiation of 
subsequent cycle. 
Part 2 Arm B 
Pomalidomide: Associated with thrombocytopenia and anemia. 
Routine hematologic monitoring as outlined in the SoA. 
Supportive therapy per local medical practice (e.g., growth factors). 
Recommendations for dose reduction and treatment discontinuation criteria are 
detailed in Section 6.7. 


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Pneumonitis 
GSK2857916: Nonclinical safety experiments have demonstrated 
the presence of progressive microscopic changes in the lungs 
(prominent alveolar macrophages associated with eosinophilic 
material; mixed perivascular/neutrophilic inflammation) in rats at all 
doses tested. 
Cases of pneumonitis, including fatal events, have been observed 
with GSK2857916 although a causal association has not been 
established.. 
Part 2 Arm A 
Bortezomib: Acute respiratory distress syndrome and acute diffuse 
infiltrative pulmonary disease of unknown etiology, such as 
pneumonitis, interstitial pneumonia, and lung infiltration have been 
reported rarely in patients receiving bortezomib. Some of these 
events have been fatal. There have been reports of pulmonary 
hypertension associated with bortezomib administration in the 
absence of left heart failure or significant pulmonary disease. 
Part 2 Arm B 
Pomalidomide: Interstitial lung disease and related events, 
including cases of pneumonitis, have been observed with 
pomalidomide. 
Monitoring for clinical signs and symptoms related to pulmonary toxicity. If a 
participant experiences new or worsening pulmonary symptoms, (e.g., cough, 
dyspnea) without obvious etiology, further diagnostic tests and management 
should be performed and further treatment with GSK2857916 delayed (refer to 
Section 6.7). 
An overall benefit/risk assessment should be considered for the participant prior to 
continuing GSK2857916 treatment. 
Further diagnostic tests and management will be implemented immediately as 
described in cases of suspected pneumonitis as described in Section 6.7. 
In the event of new or worsening cardiopulmonary symptoms, consider 
interrupting bortezomib until a prompt and comprehensive diagnostic evaluation is 
conducted. 


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Keratopathy 
(Changes to the 
Corneal Epithelium, 
Potentially Resulting 
in Vision Changes) 
GSK2857916: Changes in corneal epithelium on ocular 
examination have been frequently observed with GSK2857916 and 
was most commonly associated with keratopathy (changes in the 
corneal epithelium upon examination), dry eyes, blurred vision, 
photophobia, and changes in visual acuity. 
Participants with a history of dry eye were more prone to develop 
changes in the corneal epithelium. 
Based on available follow-up data, vision returned to, or near 
baseline in most cases.. 
Dexamethasone: Use of corticosteroids may produce posterior 
subcapsular cataracts, glaucoma with possible damage to the optic 
nerves, and may enhance the establishment of secondary ocular 
infections due to bacteria, fungi, or viruses. 
Active monitoring of the corneal epithelium and visual acuity as outlined in the 
SoA. 
Evaluation and management by an eye care professional. 
Dose modification guidelines are outlined in Section 6.7. 
Embryo-Fetal Toxicity 
GSK2857916: Nonclinical reproductive studies with GSK2857916 
have not been conducted.  Embryo-fetal toxicity is expected due to 
the cytotoxic component, cys-mcMMAF via nonspecific uptake 
and/or BCMA-mediated toxicity (due to reports of BCMA expression 
in human placental cells [Langat, 2008]). 
Use of GSK2857916 in pregnant women may cause fetal harm. 
Pregnancy testing outlined in the SoA. 
Contraception requirements detailed in Section 11.3. 
Participants receiving pomalidomide must register with any pregnancy 
prevention/controlled distribution programme in place (see SRM for details). 


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Embryo-Fetal Toxicity 
Part 2 Arm A 
Bortezomib: Bortezomib can cause fetal harm when administered 
to a pregnant woman.  Bortezomib administered to rabbits during 
organogenesis at a dose approximately 0.5 times the clinical dose 
of 1.3 mg/m2 based on body surface area caused post-implantation 
loss and a decreased number of live fetuses. 
Part 2 Arm B 
Pomalidomide: Pomalidomide is a thalidomide analogue and is 
contraindicated for use during pregnancy.  Thalidomide is a known 
human teratogen that causes severe birth defects or embryo-fetal 
death. 
Pomalidomide is available only through a pregnancy 
prevention/controlled distribution program 
Risks Related to GSK2857916 not Listed Under Potential Overlapping Toxicities 
Infusion-Related 
Reactions (IRR) 
IRRs were reported in participants treated with GSK2857916.  Most 
IRRs were Grade 1 to 2 and were manageable with treatment. 
Close monitoring for signs of IRR. 
Consider premedication for IRR in participants at risk. 
If an IRR occurs, follow the guidance in Section 7.1.6. 
Nephrotoxicity 
Nonclinical safety experiments have demonstrated primary 
glomerular injury and tubular degeneration/regeneration (in rat and 
monkey).  The morphologic changes were accompanied by large 
molecular weight proteinuria (albuminuria) and enzymuria.  Single 
cell necrosis of the kidney and bladder urothelium was also noted in 
the chronic study.  The renal changes were dose dependent and 
reversible.  Severe tubular degeneration/regeneration and marked 
glomerulonephritis as a result of immune complex disease 
associated with anti-drug antibodies led to the early euthanasia of 
one monkey following 5 weekly doses of 10 mg/kg. 
Kidney function monitoring including albumin/creatinine ratio. 
Education of participants on the need to maintain adequate urinary output. 
Dose reduction and treatment stopping criteria provided in Section 6.7. 


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Increase albumin/creatinine ratio (albuminuria) has been reported in 
participants receiving GSK2857916 not indicative of disease 
progression, and in such cases, appropriate monitoring and dose 
modification should be considered. 
Impaired Male and 
Female Fertility 
In animal studies, GSK2857916 treatment has resulted in testicular 
toxicity and adverse effects on spermatogenesis.  Reversibility of 
testicular and ovarian toxicity is unknown at this time. 
Ovarian toxicity (luteinized non-ovulatory follicles) was observed in 
a 3-week rat study (weekly dosing) and was not observed following 
12 weeks off dose.  In a 13-week rat study where drug was 
administered once every 3 weeks, these changes were not 
observed. 
Men who may wish to father children in the future will be advised to have sperm 
samples frozen and stored prior to GSK2857916 treatment. 
Women of childbearing potential who may desire offspring in the future will be 
counselled about the option of having eggs frozen and stored before treatment. 
See contraception requirements in Section 11.3. 
Potential for Other 
Laboratory 
Abnormalities 
Increased magnitude of aspartate aminotransferase (AST) relative 
to alanine aminotransferase (ALT) consistent with increased 
skeletal troponin I was observed in the single dose monkey study.  
Increased skeletal troponin I and/or creatine kinase (CK) and 
aldolase was observed in the rat 3-week study. 
Cases of elevated AST, lactate dehydrogenase (LDH) and CK 
alone or concomitant with no clear clinical correlate have been 
observed in clinical studies. 
Monitoring of laboratory parameters as outlined in the SoA. 
Participants with significant laboratory elevations (≥x3 ULN) should, where 
possible, have a sample sent for central testing of CK and LDH isoenzyme levels. 
Risks Related to Bortezomib not Listed Under Potential Overlapping Toxicities (Part 2 Arm A) 
Allergic Reactions 
Bortezomib is contraindicated for participants with hypersensitivity 
to bortezomib, boron, or mannitol, including anaphylactic reactions. 
Participants with known hypersensitivity reactions to bortezomib, boron, or 
mannitol are not allowed on study. 
Bortezomib will be discontinued if such reactions are confirmed. 
Peripheral 
Neuropathy 
Bortezomib treatment causes a peripheral neuropathy that is 
predominantly sensory; however, cases of severe sensory and 
motor peripheral neuropathy have been reported. 
Participants with ≥Grade 2 peripheral neuropathy at Screening excluded from 
study participation. 
Monitored for symptoms of neuropathy.  Dose will be adjusted accordingly. 


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Potential Risk of 
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Mitigation Strategy 
Bortezomib administered subcutaneously to reduce risk of peripheral neuropathy. 
Hypotension 
The incidence of hypotension (postural, orthostatic, and 
hypotension not otherwise specified) was 8%. 
Participants with a history of syncope, or receiving medications associated with 
hypotension, or dehydrated will be closely monitored. 
Adjustment of antihypertensive medications, hydration and administration of 
mineralocorticoids and/or sympathomimetics will follow the institutional guidelines. 
Posterior Reversible 
Encephalopathy 
Syndrome (PRES) 
PRES; formerly termed reversible posterior leukoencephalopathy 
syndrome has been reported in patients receiving bortezomib. 
Discontinue bortezomib if PRES occurs. 
The safety of reinitiating bortezomib therapy in patients previously experiencing 
PRES is not known. 
Gastrointestinal 
Toxicity 
Treatment with bortezomib can cause nausea, diarrhea, 
constipation and vomiting, sometimes requiring use of antiemetic 
and antidiarrheal medications; ileus can occur. 
Maintain adequate hydration; fluid and electrolyte replacement should be 
administered to prevent dehydration. 
Interrupt bortezomib for severe symptoms. 
Tumor Lysis 
Syndrome 
Tumor lysis syndrome has been reported with bortezomib therapy.  
Participants at risk for tumor lysis syndrome (i.e., high tumor burden) will be 
monitored and appropriate precautions instituted per local practice. 
Thrombotic 
Microangiopathy 
Cases, sometimes fatal, of thrombotic microangiopathy, including 
thrombotic thrombocytopenic purpura/hemolytic uremic syndrome 
(TTP/HUS), have been reported in patients receiving bortezomib. 
Monitor for clinical signs and symptoms potentially related to thrombotic 
microangiopathy. 
If suspected, stop bortezomib and evaluate. If the diagnosis of TTP/HUS is 
excluded, consider restarting bortezomib. 
Seizures 
Seizures have been uncommonly reported in patients without 
previous history of seizures or epilepsy. 
Special care is required when treating patients with any risk factors 
for seizures. 
Participants with a history of seizures or epilepsy will be closely monitored. 
In the event of new onset or worsening seizures, consider interrupting bortezomib 
until a prompt and comprehensive diagnostic evaluation is conducted. 
Progressive 
Multifocal 
Leukoencephalopathy 
(PML) 
Very rare cases with unknown causality of John Cunningham virus 
infection, resulting in PML and death, have been reported in 
patients treated with bortezomib.  Patients diagnosed with PML had 
prior or concurrent immunosuppressive therapy.  Most cases of 
Participants should be monitored at regular intervals for any new or worsening 
neurological symptoms or signs that may be suggestive of PML as part of the 
differential diagnosis of central nervous system problems.  If a diagnosis of PML is 
suspected, participants should be referred to a specialist in PML and appropriate 


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PML were diagnosed within 12 months of their first dose of 
bortezomib. 
diagnostic measures for PML should be initiated.  Discontinue bortezomib if PML 
is diagnosed. 
Hepatotoxicity 
Cases of acute liver failure have been reported in patients receiving 
multiple concomitant medications and with serious underlying 
medical conditions.  Other reported hepatic reactions include 
hepatitis, increases in liver enzymes, and hyperbilirubinemia. 
Only participants with well-preserved liver function per the inclusion/exclusion 
criteria will be allowed on study. 
Participants with Hepatitis B and C excluded. 
Liver function tests will be monitored per the SoA. 
In case of liver abnormalities, refer to Section 11.5 for further details. 
Liver stopping criteria outlined in Section 7.1.2. 
Cardiotoxicity 
Acute development or exacerbation of congestive heart failure and 
new onset of decreased left ventricular ejection fraction (LVEF) 
have occurred during bortezomib therapy, including reports in 
patients with no risk factors for decreased LVEF. 
Participants with significant cardiac risk factors will be excluded from study 
participation. 
Electrocardiograms will be obtained at baseline and monitored as clinically 
indicated. 
Monitoring of other cardiac parameters as clinically indicated. 
Treatment as medically indicated. 
Risks Related to Pomalidomide not Listed Under Potential Overlapping Toxicities (Part 2 Arm B) 
Venous and Arterial 
Thromboembolism 
Venous thromboembolic events (deep venous thrombosis and 
pulmonary embolism) and arterial thromboembolic events 
(myocardial infarction and stroke) have been observed in patients 
treated with pomalidomide. 
Thromboprophylaxis will be implemented as described in Section 6.6.1. 
Use of drugs that may increase thromboembolic risk (e.g., erythropoietic agents, 
estrogens, etc.) should be avoided, if possible. 
Neuropathy 
In studies combining pomalidomide with dexamethasone, 
neuropathy including peripheral neuropathy reported. 
Monitor for symptoms of neuropathy. 
Severe Cutaneous 
Reactions 
Severe cutaneous reactions including Stevens-Johnson syndrome 
(SJS), toxic epidermal necrolysis (TEN) and drug reaction with 
eosinophilia and systemic symptoms (DRESS) have been reported. 
Consider dose interruption or discontinuation for Grade 2-3 skin rash. 
Permanently discontinue lenalidomide for Grade 4 rash, exfoliative or bullous 
rash, or for other severe cutaneous reactions such as SJS, TEN or DRESS. 


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Hypersensitivity 
Hypersensitivity, including angioedema, anaphylaxis, and 
anaphylactic reactions have been reported. 
Discontinue pomalidomide for angioedema or anaphylaxis. 
Dizziness and 
Confusional State 
In studies combining pomalidomide with dexamethasone, dizziness 
and confusional state have been reported. 
Participants should avoid situations where dizziness or confusional state may be a 
problem and not to take other medications that may cause dizziness or 
confusional state without adequate medical advice. 
Second Primary 
Malignancies 
Cases of acute myelogenous leukemia have been reported in 
patients receiving pomalidomide as an investigational therapy 
outside of multiple myeloma (MM). 
Participants will be monitored for the occurrence of new malignancies. 
Tumor Lysis 
Syndrome 
Tumor lysis syndrome may occur in patients treated with 
pomalidomide. 
Participants at risk for tumor lysis syndrome (i.e., high tumor burden) will be 
monitored and appropriate precautions instituted per local practice. 
Hepatotoxicity 
Hepatic failure, including fatal cases and elevated levels of ALT and 
bilirubin reported. 
Only participants with well-preserved liver function per the inclusion/exclusion 
criteria will be allowed on study. 
Participants with Hepatitis B and C excluded. 
Liver function tests will be monitored per the SoA. 
In case of liver abnormalities, refer to Section 11.5 for further details. 
Liver stopping criteria outlined in Section 7.1.2. 
Risks Related to Dexamethasone not Listed Under Potential Overlapping Toxicities (Part 2 Arm A and Arm B) 
Vaccinations 
Administration of live or live, attenuated vaccines is contraindicated 
in patients receiving immunosuppressive doses of corticosteroids. 
Killed or inactivated vaccines may be administered.  However, the response to 
such vaccines cannot be predicted.  
Immunizations with live attenuated vaccines are not allowed in the study. 
Viral infections 
Chickenpox and measles can have a more serious or even fatal 
course in pediatric and adult participants on corticosteroids. 
Participants who have not had these diseases, particular care should be taken to 
avoid exposure.  If exposed to chickenpox, prophylaxis with VZIG may be 
indicated. If exposed to measles, prophylaxis with immune globulin may be 
indicated. 


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Allergic or 
Hypersensitivity 
Reactions 
Contraindicated in patients who are hypersensitive to any 
components of this product. 
Rare instances of anaphylactoid reactions have occurred in patients 
receiving corticosteroid therapy. 
Enrolment of participants with known hypersensitivity reactions to components of 
the formulation are prohibited. 
Endocrine 
Hypothalamic-pituitary adrenal axis suppression with the potential 
for corticosteroid insufficiency after withdrawal of treatment. 
Avoid rapid withdrawal of corticosteroids if used at high doses for a prolonged 
period. 
Gastrointestinal 
Use with caution in active or latent peptic ulcers, diverticulitis, fresh 
intestinal anastomoses, and nonspecific ulcerative colitis, since they 
may increase the risk of a perforation, or GI bleeding. 
Hematologic parameters will be monitored as outlined in the SoA. 
New cases of anemia should be fully investigated, including the possibility of 
gastrointestinal bleeding. 
Musculoskeletal 
Decreased bone formation and increase bone resorption both 
through their effect on calcium regulation (i.e., decreasing 
absorption and increasing excretion) and inhibition of osteoblast 
function.  Acute myopathy has been observed with the use of high 
doses of corticosteroids, most often occurring in patients with 
disorders of neuromuscular disorders, or in patients receiving 
neuromuscular blocking drugs. 
Ongoing monitoring of adverse events (AEs). 
Neuropsychiatric 
Psychic derangements may appear when corticosteroids, ranging 
from mild symptoms to severe depression, to frank psychotic 
manifestations.  Also, existing emotional instability or psychotic 
tendencies may be aggravated by corticosteroids. 
Ongoing monitoring of AEs. 
Cardiotoxicity  
Average and large doses of corticosteroids can cause elevation of 
blood pressure, sodium and water retention, and increased 
excretion of potassium. 
Participants with significant cardiovascular risk factors will be excluded from study 
participation. 


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Potential Risk of 
Clinical Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Risks from Study Procedures 
Bone Marrow 
Aspiration/biopsy 
Pain, infection, bleeding may occur after the procedure. 
Participants will be treated according to institutional practice. 
Incidental Findings 
During Image 
Acquisition 
During the acquisition of imaging data (e.g., magnetic resonance 
imaging, computed tomography, positron emission tomography), 
non-MM disease or clinically relevant abnormalities could be found 
by the radiographer performing the exams. 
Copies of all medical images that include non-MM disease, clinically relevant 
abnormalities will be shared with the site for storage. 
*Refer to GSK2857916 Investigator’s Brochure and prescribing information for pomalidomide, bortezomib and dexamethasone for further information. 
 


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2.4.2. 
Benefit Assessment  
GSK2857916 Monotherapy (Part 1) 
The study population enrolled for Part 1 has a high unmet medical need.  Participants 
failing multiple lines of prior treatments do not have many therapeutic options left, and 
even if response can be achieved with currently available drugs, it is usually of short 
duration. 
Data from single-agent study BMA117159 support testing GSK2857916 in Japanese 
participants with RRMM failing currently available treatments. 
The FTIH study BMA117159, as of 31 August 2018, indicated that GSK2857916 
monotherapy administered at 3.4 mg/kg is active in participants with RRMM (n=35), 
with an ORR of 60% (95% CI: 42.1, 76.1) and a mPFS was 12.0 months (95% CI: 3.1, 
NE) [Trudel, 2019].  
In the ongoing Phase II study 205678/DREAMM-2 (NCT03525678), the 2 single agent 
doses (2.5 mg/kg and 3.4 mg/kg) are being studied via a 2-arm, randomized design in 
participants who have failed at least 3 prior lines of anti-myeloma therapy, including an 
anti-CD38 antibody, and who are refractory to an IMiD and a proteasome inhibitor.  Both 
dose levels, 2.5 and 3.4 mg/kg, have a positive benefit/risk profile.  As of the cut-off date 
of 31 January 2020, the ORR in the 2.5 mg/kg treatment was 31% (97.5% CI: 21.7, 43.6) 
and in the 3.4 mg/kg treatment 35% (97.5% CI: 24.8, 47.0).  Overall, there were no new 
safety signals identified in the 205678 study, and the profile of AEs was similar to the 
experience in DREAMM-1 for both arms.  Primary analysis show both dose levels of 
GSK2857916 (2.5 and 3.4 mg/kg) to have a positive benefit/risk profile. 
Combination Therapy of GSK2857916 with Standard of Care (Part 2) 
Increased anti-myeloma activity has been demonstrated when additional agents, with 
individual activity, are given in combination with Bor/Dex or Pom/Dex, including 
monoclonal antibodies.  The combination treatment of a highly active drug, 
GSK2857916, with Bor/Dex or Pom/Dex is therefore expected to result in increased 
benefit to MM patients who have relapsed after at least 1 prior line of therapy.  
Preliminary data from Study 207497, which is an ongoing Phase I/II study evaluating the 
safety and clinical activity of GSK2857916 when given in combination with Bor/Dex in 
participants with RRMM, indicates that the combination of GSK2857916 at 2.5 mg/kg 
dose with Bor/Dex is safe and tolerable without DLTs and is showing early evidence of 
activity.  The combination treatment of a highly active drug GSK2857916 with Pom/Dex 
is relatively safe with early signs of clinical activity as measured by objective response in 
an ongoing Phase I/II study conducted by the MCRN (Study 209418).  It is reasonable to 
hypothesize that such combination will benefit MM patients, who are refractory to 
currently available treatments. 


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2.4.3. 
Overall Benefit: Risk Conclusion  
GSK2857916 Monotherapy (Part 1) 
Data from the FTIH study, BMA117159, demonstrate a manageable safety profile with 
thrombocytopenia and corneal events being the most frequently reported AEs.  The 
corneal events most often manifested as blurry vision, photophobia, and dry eyes though 
a range of symptoms was possible, including increased lacrimation, pain and pruritus. 
Most events were Grade 1/2 and improved with dose interruptions and/or reduction. 
GSK2857916 has shown strong single-agent activity.  The confirmed ORR in Part 2 
(MM) was 60% (95% CI, 42.1, 76.1) with 6% achieving sCR, 9% achieving CR, 40% 
achieving VGPR, and 6% achieving PR.  The estimated mPFS of participants in Part 2 
(MM) was 12.0 months (95% CI, 3.1%, NE). For participants refractory to both 
immunomodulators and proteasome inhibitors, the mPFS was 7.9 months (95% CI, 2.3, 
NE).  Although maximum clinical benefit was observed at the 3.4 mg/kg dose level, 
frequent dose delays and dose reductions were required to manage AEs including 
thrombocytopenia/platelet count decreased and corneal events. 
Taking into account the measures taken to minimize risk to participants in this study, the 
potential risks identified in association with GSK2857916 are justified by the anticipated 
benefits that may be afforded to participants with RRMM. 
Combination Therapy of GSK2857916 with Standard of Care (Part 2) 
Considering the observed clinical activity of GSK2857916 as a single agent in 
participants with RRMM, and the observed safety profile in mono- and combination 
therapy, it is reasonable to assume that the combination of GSK2857916 with Bor/Dex or 
Pom/Dex may offer additional benefit to patients with RRMM. 
Although there is the potential for overlapping toxicities, it is anticipated that 
combination therapy of GSK2857916 with Bor/Dex or Pom/Dex will have an acceptable 
risk/benefit profile, with manageable toxicities. 
Considering the measures taken to minimize risk to participants, the potential risks 
associated with GSK2857916 when combined with Bor/Dex or Pom/Dex are justified by 
the anticipated benefits that may be afforded to participants with MM. 
3. 
OBJECTIVES AND ENDPOINTS  
The purpose of this study is to evaluate safety, PK, PD, immunogenicity and early 
efficacy of the GSK2857916 in Japanese participants with RRMM who have been 
pretreated with at least 2 regimens of anti-myeloma drugs.  See Table 5 for the primary, 
secondary, and exploratory objectives, along with the corresponding endpoints. 


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Table 5 
Objectives and Endpoints for Study 207504 
Objectives 
Endpoints 
Primary Objective 
To evaluate safety, tolerability of GSK2857916 in 
Japanese participants with RRMM. 
Number of participants with DLTs 
Adverse events (AEs) and changes in clinical signs 
and laboratory parameters. 
Secondary Objectives 
To evaluate pharmacokinetic (PK) profile of 
GSK2857916 and cysteine maleimidocaproyl 
monomethyl auristatin F (cys-mcMMAF) after IV 
single and repeat dose administration in Japanese 
participants with RRMM. 
GSK2857916 and cys-mcMMAF PK parameters 
following IV single and repeat dose administration as 
data permit (e.g., AUCs, Cmax, tmax, CL, Vss, t½ 
[single dose], Ceoi, Ctrough, and Rac (Ceoi and 
Ctrough) [repeat dose]). 
To assess anti-drug antibody (ADA) formation after IV 
single and repeat dose administration of 
GSK2857916. 
ADA incidence and titers after IV single and repeat 
dosing of GSK2857916. 
To investigate the initial anti-tumor activity of 
GSK2857916 in Japanese participants with RRMM. 
Clinical activity measured as Overall Response Rate 
(ORR) and Clinical Benefit Rate (CBR) which are 
defined as follows: 
 ORR: the percentage of participants achieving 
confirmed partial response or better (PR) 
 CBR: the percentage of participants with 
minimal response (MR) or better 
4. 
STUDY DESIGN  
4.1. 
Overall Design  
This is a Phase 1, open label, dose escalation study to investigate safety, tolerability, PK, 
PD, immunogenicity and clinical activity of GSK2857916 when given as monotherapy 
on a once every 21 days schedule (Part 1), or given in combination with Bor/Dex on a 
once every 21 days schedule (Part 2 Arm A) or with Pom/Dex on a once every 28 days 
schedule (Part 2 Arm B).  The study will consist of 2 parts.  Part 1 is a dose escalation 
phase to evaluate the safety and tolerability of up to 2 dose levels of GSK2857916 
monotherapy.  Part 2 of the study will evaluate the safety and tolerability of 1 dose level 
of GSK2857916 in combination with 2 SoC regimens: Part 2 Arm A - GSK2857916 with 
Bor/Dex, and Part 2 Arm B - GSK2857916 with Pom/Dex.  
CCI


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The maximum number of participants for Part 1 will be up to 12 participants, up to 
6 participants each for 2.5 mg/kg cohort and 3.4 mg/kg cohort.  The maximum number of 
participants for Part 2 will be up to 12, up to 6 participants each for Arm A and Arm B 
based on 3 + 3 design. 
The dose escalation model is based on 3 + 3 design (Figure 2).  The GSK2857916 will be 
administered (IV) via 30 min infusion Q3W (21 days = 1 cycle) or Q4W 
(28 days = 1 cycle).  The initial anti-tumor activity of GSK2857916 based on response 
assessment criteria as defined by International Myeloma Working Group (IMWG) 2016 
will also be assessed during the study [Kumar, 2016]. 
EOS Definition: Following 21 months post last subject first dose, Study 207504 
(DREAMM-11) will move into the PACT phase where the study remains open only to 
provide continued access to study treatment for study participants who are continuing to 
derive clinical benefit. At that time, the collection of new data for participants who no 
longer receive study treatment will stop entirely and the clinical trial database will be 
closed. Those participants still benefiting from study drug in the opinion of their treating 
physician may continue to receive study drug and only SAEs, AEs leading to treatment 
discontinuation, overdose and pregnancy cases, and pre-specified ocular data will be 
reported directly to GSK. The EOS is defined as the date of the last visit of the last 
participant in the study (e.g. last dose plus 70 days AE reporting period) or last scheduled 
procedure shown in the Schedule of Activities for the last participant in the study. 
 


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Figure 2 
Study Schematic  
 
 
 


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3 + 3 Dose Escalation: Dose-escalation will follow a 3 + 3 dose-escalation procedure as 
shown in Table 6.  The first participant in each dose cohort should complete C1 to enrol 
subsequent participants.  Evaluation of available safety data from at least 3 participants 
who have completed a minimum of 21 days (1 cycle: 21 days) or 28 days (1 cycle: 
28 days) is required to start the next dose cohort.  Dose-escalation will be determined 
considering all available information on AEs occurred in the DLT observation period.  
Refer to Table 6 for more details.  Dose levels to be tested in the study are provided in 
Table 7, Table 8, and Table 9. 
GSK may consult with safety and efficacy evaluation committee as needed. Safety and 
efficacy evaluation committee will propose GSK necessity of additional participant. 
Table 6 
3 + 3 Dose-Escalation Guidelines 
Number of Participants with DLT at a Given 
Dose Level 
Action 
0 out of 3 participants 
Escalate to next dose level 
1 out of 3 participants 
Accrue 3 additional evaluable participants at 
current dose level for a total of 6 evaluable 
participants 
 
If 0 of the additional 3 participants 
experience a dose-limiting toxicity (DLT), 
proceed to next dose level. 
 
If 1 or more participants experience a 
DLT, the dose-escalation is stopped 
1 out of 6 participants 
Escalate to next dose level 
2 or more participants in a dosing cohort (up to 6 
participants) 
Dose-escalation will be stopped. 
Table 7 
Dose Levels for Part 1 
Dose Level 
GSK2857916 (mg/kg) 
0, starting dose 
2.5 
1 
3.4 
 
Table 8 
Dose Level for Part 2 Arm A 
Dose Level 
GSK2857916 (mg/kg) 
0, starting dose 
2.5 
 
Table 9 
Dose Levels for Part 2 Arm B 
Dose Level 
GSK2857916 (mg/kg) 
0, starting dose 
2.5 (C1) and 1.9 (C2+) 
 


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4.1.1. 
Dose-Limiting Toxicity  
Any participant who received at least one dose of the study treatment will be evaluated 
for DLTs in Part 1.  In Part 2, any participant who received a complete infusion of 
GSK2857916 and at least 75% of planned doses of Bor/Dex or Pom/Dex by the end of 
C1 is considered DLT-evaluable.  Safety data together with DLTs will be reviewed prior 
to opening enrollment into subsequent cohorts. 
In Part 1 and Part 2 Arm A, DLT is defined as any observed toxicity in the first 21 days 
of treatment cycle.  In Part 2 Arm B, DLT is defined as any observed toxicity in the first 
28 days of treatment cycle.  If 1 of 3 participants experiences a DLT at a particular dose 
level, 3 additional participants will be enrolled at that dose level. 
In Part 1, participants who have been withdrawn from the study for reasons other than 
toxicity but prior to completion of DLT observation period will be replaced.  Participants 
in Part 2 who have received less than 1 full dose of GSK2857916, or less than 75% of 
planned doses of Bor/Dex or Pom/Dex, or who have been withdrawn from the study for 
reasons other than toxicity but prior to completion of DLT observation period will be 
replaced. 
A following event occurring within the DLT reporting period (first 21 days cycle or first 
28 days cycle) will be considered a DLT if its relationship to the investigational agent 
cannot be ruled out: 
Hematologic: 
 
Grade 3 or greater febrile neutropenia lasting >48 hours despite adequate treatment 
 Grade 3 is defined as ANC <1000/mm3 with a single temperature of >38.3C or a 
 
sustained temperature of ≥ 38C for more than 1 hour 
 Grade 4 is defined as ANC <1000/mm3 with a single temperature of >38.3C or a 
 
sustained temperature of ≥38C for more than one hour, with life-threatening 
 
consequences and urgent intervention indicated 
 
Grade 4 thrombocytopenia <25,000/mm3 accompanied by clinically significant 
bleeding. 
Non-hematologic except corneal toxicity: 
 
Any Grade 3 or greater non-hematologic toxicity (other than corneal events) which 
does not resolve with appropriate supportive treatment within 48 hours 
 
Any Grade 3 or greater non-hematologic laboratory value if 
 The laboratory abnormality persists for >48 h despite supportive treatment 
 The abnormality leads to hospitalization. 
Corneal toxicity: 
 
Grade 4 per the modified corneal grading scale (See Appendix 7). 


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Other organ-specific toxicity: 
 
Liver toxicity meeting pre-specified GSK liver stopping criteria. 
A participant who develops a DLT will be allowed to stay on study if the toxicity did not 
meet stopping criteria and recovered to  Grade 1 if the investigator and medical monitor 
agree that for a given participant the benefits may outweigh the risks. 
4.2. 
Scientific Rationale for Study Design  
GSK2857916 is the first-in-class ADC targeting BCMA.  Clinical data for GSK2857916 
monotherapy from 35 participants in the Study BMA117159 indicate an ORR of 60% 
[95% CI: 42.1, 76.1], with 54% of participants (n=19) having deep responses of VGPR or 
better.  The median DoR was 14.3 months (95% CI: 10.6, NR); the mPFS in this 
population was 12.0 months [95% CI: 3.1, NE].  The majority of participants (57%) had 
5 or more prior treatments.  Of note, the ORR for participants refractory to both IMiDs 
and proteasome inhibitors (n=32) was 56% (95% CI: 37.7, 73.6). 
The response rate observed in this population is higher than response rates observed in 
similarly defined patient populations treated with other recently approved drugs (ORR 
ranging from 23.7% to 33.1% for carfilzomib, pomalidomide and daratumumab) 
[Siegel, 2012; Usmani, 2016; Kumar, 2008].  The most frequent AEs were corneal events 
and thrombocytopenia/platelet count decrease, which were manageable following 
protocol-defined dose modification guidelines.  Given the evidence of clinical activity 
and manageable safety/tolerability profile demonstrated to date, the current evidence 
supports further development for GSK2857916 monotherapy.  Based on the results of 
BMA117159, the dosing regimen for GSK2857916 monotherapy is determined for 
further global development. 
IMiD and proteasome inhibitors have been a cornerstone in the treatment of MM for 
many yearsKumar.  Combining active agents with lenalidomide/dexamethasone or 
bortezomib/dexamethasone treatment may yield improved patient outcomes with 
acceptable toxicity profiles, establishing global SoC regimens. 
Additional preclinical studies have been performed to evaluate the anti-tumor activity of 
GSK2857916 in combination with bortezomib, pomalidomide or dexamethasone in 
2 established MM xenograft mouse models.  GSK2857916 combinations with 
pomalidomide or bortezomib provided additional benefit compared to each single agent 
by significantly increasing survival in both mouse models.  
Based on the nonclinical data available for the GSK2857916/pomalidomide combination 
and the clinical data for GSK2857916 monotherapy, it is therefore hypothesized that the 
combination of GSK2857916 with Bor/Dex or with Pom/Dex may result in significant 
additive or synergistic effect. 
Preliminary data from the ongoing Phase I/II study (study 207497) evaluating the safety 
and clinical activity of GSK2857916 when given in combination with Bor/Dex indicates 
that the combination of GSK2857916 at 2.5 mg/kg dose with Bor/Dex is safe and 
tolerable without DLTs and is showing early evidence of activity.  Initial safety and 


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efficacy data of GSK2857916 at multiple dose levels in combination with Pom/Dex Q4W 
has been evaluated in an ongoing Phase I/II study conducted by the MCRN 
(study 209418).  Preliminary data showed that the GSK2857916 with Pom/Dex 
combination has resulted in early signal of clinical activity.  The observed safety profile 
of GSK2857916 with Pom/Dex is consistent with the safety profile of GSK2857916 and 
pomalidomide. 
Given the evidence of clinical activity and manageable safety/tolerability profile 
demonstrated to date, the current evidence supports further development for 
GSK2857916 combination therapy. 
Based on the results of studies 207497 and 209418, the dosing regimens for 
GSK2857916 in combination with Bor/Dex or Pom/Dex are determined for further global 
development. 
This is the first study targeting Japanese MM participants.  Therefore, the primary 
objective of this study is to evaluate tolerability and safety of GSK2857916 monotherapy 
on a Q3W schedule in Part 1, and GSK2857916 in combination with Bor/Dex on a Q3W 
schedule and with Pom/Dex on a Q4W schedule in Part 2 in Japanese participants with 
RRMM.  To evaluate tolerability and safety, the study uses a standard 3 + 3 dose-
escalation design. 
4.3. 
Justification for Dose  
4.3.1. 
Justification for Dose for Part 1  
In the ongoing BMA117159 study at the tested dose range of 0.03 to 4.6 mg/kg, 
GSK2857916 has demonstrated a manageable safety profile with thrombocytopenia 
and/or platelet count decreased and corneal events as the most commonly reported 
events.  3.4 mg/kg was selected as the RP2D after careful analysis of data from dose 
escalation across 10 dose levels and was based on the following: 
 
At 3.4 mg/kg, the ORR was 100% in Part 1 which was substantially higher than 
the ORR observed at all other dose levels. 
 
There were no DLTs across all tested dose levels, but the next higher dose of 
4.6 mg/kg resulted in decreased tolerability.  
 
The overall safety profile was manageable at the 3.4 mg/kg dose.  
 
Estimated receptor binding saturation is achieved at doses ≥ 1.92 mg/kg. 
Based on these results from the FTIH study (BMA117159), this study is designed to 
evaluate safety and tolerability of 3.4 mg/kg, which is determined as RP2D in Japanese 
patients.  Also, GSK2857916 is administered to Japanese patients for the first time in this 
study.  Therefore, 2.5 mg/kg, which is one level below the RP2D, is set as starting dose in 
order to conduct the study safely when administered on a Q3W schedule. 1.92 mg/kg 
may be explored if 2.5 mg/kg is not tolerated. 


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4.3.2. 
Justification for Dose for Part 2  
4.3.2.1. 
GSK2857916  
Arm A 
GSK2857916 dose of 2.5 mg/kg Q3W is currently being evaluated in combination with 
bortezomib and dexamethasone in study 207497 in RRMM participants who have failed 
at least 1 prior line of therapy.  Based on data from 15 participants treated at the 
GSK2857916 dose of 2.5 mg/kg Q3W, followed on study for 1 to 14 cycles 
(6 participants with a range of 8 to 14 cycles, an average of 11 cycles and a median of 
12 cycles as of 26 November 2019), this combination dose has been shown to have an 
acceptable safety profile, with an AE profile consistent with each of the AE profiles for 
bortezomib, dexamethasone, and GSK2857916 monotherapy. 
The PK of GSK2857916 were evaluated in combination with bortezomib and 
dexamethasone.  Based on interim PK data, as anticipated, GSK2857916 did not appear 
to impact the PK of bortezomib, while Bor/Dex did not appear to alter the PK of 
GSK2857916. 
Based on this information, a dose of 2.5 mg/kg of GSK2857916 was selected as 
recommended phase III dose (RP3D) when combined with bortezomib and 
dexamethasone. 
In Study 207504, as of the data cut-off date of 09 July 2019, 2.5 mg/kg cohort has 
enrolled 4 participants.  There were no DLTs and AEs leading to treatment 
discontinuation and study withdrawal in 2.5 mg/kg cohort.  AE profile of 2.5 mg/kg in 
Japanese participants was generally consistent with known safety profile of 
GSK2857916.  Therefore, 2.5 mg/kg was considered tolerable in Japanese participants.  
In addition, preliminary PK data showed that the ADC GSK2857916 and total mAb 
plasma concentrations in Japanese participants are similar to concentrations observed in 
participants in Study 205678.  Consequently, notable inter-ethnic differences in ADC and 
total mAb exposures are not observed.  Furthermore, same dose of Bor/Dex has been 
approved and used in both Japan and overseas. 
Therefore, Part 2 Arm A is designed to evaluate safety and tolerability of 2.5 mg/kg, 
which is determined as RP3D when combined with bortezomib and dexamethasone, in 
Japanese patients. 
Arm B 
GSK2857916 at multiple dose levels Q4W is currently being evaluated in combination 
with Pom/Dex in the Phase I/II study 209418 conducted by the MCRN in RRMM 
participants who have failed at least 1 prior line of therapy.  As of 08 January 2020, 
11 participants have received GSK2857916 at 1.92 mg/kg dose, and 7 participants at 
2.5 mg/kg dose Q4W in combination with Pom/Dex Q4W. 
Based on the dose escalation criteria, both 1.92 mg/kg and 2.5 mg/kg doses of 
GSK2857916 have been considered to be safe with early signs of clinical activity when 


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administered in combination with Pom/Dex, Q4W.  The observed safety profile of 
GSK2857916 with Pom/Dex is consistent with the safety profile of GSK2857916 and 
pomalidomide.  All 7 participants in the 2.5 mg/kg dose level experienced ocular toxicity 
by C3 of therapy requiring dose interruptions and dose reductions to 1.92 mg/kg Q4W.  
Despite these dose modifications, all participants achieved deep responses (VGPR or 
CR). 
GSK2857916 initial dose of 1.92 mg/kg was better tolerated without need for dose 
reduction of GSK2857916 when administered in combination with Pom/Dex Q4W.  
Preliminary early data showed a trend for early signs of clinical activity. 
Based on the totality of the data from study 209418, the dosing regimen for Phase III 
study of GSK2857916 plus pomalidomide and dexamethasone will be 2.5 mg/kg in C1 
followed by 1.9 mg/kg in Cycle 2 and beyond (C2+) when combined with Pom/Dex 
Q4W for maximizing the potential efficacy while limiting the dose delay/interruption; the 
dose of GSK2857916 in C2+ was changed from 1.92 mg/kg to 1.9 mg/kg to be consistent 
across the GSK2857916 studies. 
In Study 207504, as of the data cut-off date of 09 July 2019, 2.5 mg/kg cohort has 
enrolled 4 participants.  There were no DLTs and AEs leading to treatment 
discontinuation and study withdrawal in 2.5 mg/kg cohort.  AE profile of 2.5 mg/kg in 
Japanese participants was generally consistent with known safety profile of 
GSK2857916.  Therefore, 2.5 mg/kg was considered tolerable in Japanese participants.  
In addition, preliminary PK data showed that the ADC GSK2857916 and total mAb 
plasma concentrations in Japanese participants are similar to concentrations observed in 
participants in Study 205678.  Consequently, notable inter-ethnic differences in ADC and 
total mAb exposures are not observed.  Furthermore, same dose of Pom/Dex has been 
approved and used in both Japan and overseas. 
Therefore, Part 2 Arm B is designed to evaluate safety and tolerability of the dosing 
regimen, which will be used for Phase III study when combined pomalidomide and 
dexamethasone, in Japanese patients. 
4.3.2.2. 
Bortezomib/Dexamethasone Dose  
Bor/Dex will be administered at the approved and clinically used dose.  Details on 
Bor/Dex administration are provided in Section 6.2.1. 
4.3.2.3. 
Pomalidomide/Dexamethasone Dose  
Pom/Dex will be administered at the approved and clinically used dose.  Details on 
Pom/Dex administration are provided in Section 6.2.2. 
4.4. 
End of Study Definition  
A participant is considered to have completed the study if he/she has completed all 
phases of the study including the last visit or the last scheduled procedure shown in the 
Schedule of Activities (SoA). 


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A participant will be also considered to have completed the study if the participant has 
received at least 1 dose of the study treatment and has died. 
A participant will be considered to have withdrawn from the study if any of the following 
apply: 
 
The participant has not died and is lost to follow-up. 
 
The participant has withdrawn consent. 
 
The participant is no longer being followed at the investigator’s discretion. 
 
The study is terminated prematurely. 
A final DCO representing the end of data collection, prior to the EOS, is defined as 21 
months post last subject first dose. Following the final DCO date the study will move into 
the PACT phase and the clinical study database will be closed to new data. Participants 
who are receiving study treatment may continue to receive study treatment if they are 
gaining clinical benefit as assessed by the investigator until they meet any protocol-
defined treatment discontinuation criteria. Although the clinical study database will be 
closed at the time of the final DCO date, the study remains open until all participants 
discontinue study treatment and complete the 70-day safety follow-up and the EOS 
definition is reached. 
The EOS is defined as the date of the last visit of the last participant in the study (e.g. last 
dose plus 70 days AE reporting period) or last scheduled procedure shown in the 
Schedule of Activities for the last participant in the study. A participant is considered to 
have completed the study if he/she has completed all periods of the study including the 
last visit or the last scheduled procedure shown in the SoA. 
5. 
STUDY POPULATION  
Prospective approval of protocol deviations to recruitment and enrolment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
Specific information regarding warnings, precautions, contraindications, AEs, and other 
pertinent information on the GSK study treatment that may impact participant eligibility 
is provided in the IB.  Deviations from inclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability or 
participant safety.  Therefore, adherence to the criteria as specified in the protocol is 
essential. 
5.1. 
Inclusion Criteria  
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
28. Provide signed written informed consent, which includes compliance with the 
requirements and restrictions listed in the consent form 
29. Male or female, 20 years or older (at the time consent is obtained) 


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30. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 
(Appendix 6) 
31. Histologically or cytologically confirmed diagnosis of MM as defined according to 
IMWG 2014 [Rajkumar, 2014], criteria in a participant who fulfills all of the 
following: 
i. 
has undergone stem cell transplant, or is considered transplant ineligible, 
ii. 
Part 1: has received at least 2 prior lines of anti-myeloma drugs containing at 
least 1 proteasome inhibitor and at least 1 immunomodulator, 
Part 2: has received at least 1 prior line of anti-myeloma drugs, 
iii. 
Part 1: has demonstrated progression on, or within 60 days of completion of 
the last therapy. 
Part 2: has documented disease progression during or after their most recent 
therapy. 
32. Has measurable disease with at least one of the following: 
a. Serum M-protein ≥ 0.5 g/dL (≥ 5 g/L) 
b. Urine M-protein ≥200 mg/24h 
c. Serum free light chain (FLC) assay: Involved FLC level ≥ 10 mg/dL 
(≥ 100 mg/L) and an abnormal serum FLC ratio (<0.26 or >1.65). 
33. Participants with a history of autologous stem cell transplant are eligible for study 
participation provided the following eligibility criteria are met: 
a. Transplant was > 100 days prior to study enrolment 
b. No active infection. 
34. Female Participants: Contraceptive use by women should be consistent with local 
regulations regarding the methods of contraception for those participating in clinical 
studies. 
A female participant is eligible to participate if she is not pregnant or breast feeding, 
and at least one of the following conditions applies: 
 
Is not a woman of childbearing potential (WOCBP) 
OR 
 
For Part 1 and Part 2 Arm A: 
Is a WOCBP and using a contraceptive method that is highly effective (with a 
failure rate of <1% per year), preferably with low user dependency, during the 
treatment period and for 4 months after the last dose of GSK2857916, and 
7 months from the last dose of bortezomib (only Part 2 Arm A), and agrees not 
to donate eggs (ova, oocytes) for the purpose of reproduction during this period. 
The investigator should evaluate the effectiveness of the contraceptive method 
in relationship to the first dose of study treatment. 
A WOCBP must have a negative highly sensitive serum pregnancy test (as 
required by local regulations) within 72 hours before the first dose of study 
treatment and agree to use effective contraception during the study and for 


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4 months after the last dose of GSK2857916, and 7 months from the last dose of 
bortezomib (only Part 2 Arm A).  
For Part 2 Arm B: 
Due to pomalidomide being a thalidomide analogue with risk for embryo-fetal 
toxicity and prescribed under a restricted distribution program, WOCBP 
participants will be eligible if they commit either to abstain continuously from 
heterosexual sexual intercourse or to use 2 methods of reliable birth control, 
beginning 4 weeks prior to initiating treatment with pomalidomide, during 
therapy, during dose interruptions and continuing for 4 weeks following 
discontinuation of pomalidomide treatment.  Thereafter, WOCBP participants 
must use a contraceptive method that is highly effective (with a failure rate of 
<1% per year) for a further 3 months, and agrees not to donate eggs (ova, 
oocytes) for the purpose of reproduction during this period. 
Two negative pregnancy tests must be obtained prior to initiating pomalidomide 
therapy.  The first test should be performed within 10 to 14 days and the second 
test within 24 hours prior to prescribing pomalidomide therapy. 
The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
35. Male Participants: Contraceptive use by men should be consistent with local 
regulations regarding the methods of contraception for those participating in clinical 
studies.  
Male participants are eligible to participate if they agree to the following from the 
time of first dose of study treatment until 6 months after the last dose of 
GSK2857916, 4 months after the last dose of bortezomib (only Part 2 Arm A), and 
4 weeks after the last dose of pomalidomide (only Part 2 Arm B) to allow for 
clearance of any altered sperm:  
 
Refrain from donating sperm 
PLUS either: 
 
Be abstinent from heterosexual intercourse as their preferred and usual lifestyle 
(abstinent on a long term and persistent basis) and agree to remain abstinent.  
OR 
 
Must agree to use contraception/barrier as detailed below: 
Agree to use a male condom, even if they have undergone a successful vasectomy, 
and female partner to use an additional highly effective contraceptive method with a 
failure rate of <1% per year as when having sexual intercourse with a woman of 
childbearing potential (including pregnant females). 
36. All prior treatment-related toxicities (defined by National Cancer Institute- Common 
Toxicity Criteria for Adverse Events (NCI-CTCAE), version 4.03, must be ≤Grade 1 
at the time of enrolment except for alopecia.  Participants with Grade 2 peripheral 
neuropathy can be enrolled into Part 1 and Part 2 Arm B but not into Part 2 Arm A. 


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37. Adequate organ system functions as defined in Table 10 or Table 11. 
Table 10 
Criteria for Determining Adequate Organ System Function for Part 1 
System 
Laboratory Values 
Hematologic 
Absolute neutrophil count (ANC) 
1.0 X 109/L 
Hemoglobin 
8.0 g/dL 
Platelets 
50 X 109/L 
Hepatic 
 
Total bilirubin 
≤1.5X ULN  
(Isolated bilirubin ≥1.5xULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%) 
ALT 
2.5 X ULN 
Renal 
eGFR1 
Spot urine (albumin/creatinine ratios via spot 
urine) 
30 mL/min/ 1.73 m2  
<500 mg/g (56 mg/mmol) 
Cardiac 
LVEF (ECHO) 
45% 
1. eGRF via Modified Diet in Renal Disease 
 
Table 11 
Criteria for Determining Adequate Organ System Function for Part 2 
System 
Laboratory Values 
Hematologic 
Absolute neutrophil count (ANC) 
1.5 X 109/L 
Hemoglobin 
8.0 g/dL 
Platelets 
75 X 109/L 
Hepatic 
 
Total bilirubin 
≤1.5X ULN  
(Isolated bilirubin ≥1.5xULN is acceptable if bilirubin is 
fractionated and direct bilirubin <35%) 
ALT 
2.5 X ULN 
Renal 
eGFR1 
Spot urine (albumin/creatinine ratios via spot 
urine) 
40 mL/min/1.73 m2  
<500 mg/g (56 mg/mmol) 
Cardiac 
LVEF (ECHO) 
45% 
1. eGFR via Modified Diet in Renal Disease 
 
5.2. 
Exclusion Criteria  
Participants are excluded from the study if any of the following criteria apply: 
38. Systemic anti-tumor-therapy within 14 days, or plasmapheresis within 7 days prior to 
the first dose of study treatment. 
39. Symptomatic amyloidosis, active ‘polyneuropathy, organomegaly, endocrinopathy, 
myeloma protein, and skin changes’ (POEMS) syndrome, active plasma cell 
leukemia at the time of screening. 


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40. Use of an investigational drug within 14 days or 5 half-lives, whichever is shorter, 
preceding the first dose of study treatment. Prior treatment with a monoclonal 
antibody within 30 days of receiving the first dose of study treatment. Prior BCMA 
targeted therapy. 
41. History of an allogeneic stem cell transplant. 
42. Current use of prohibited medications/device or planned use of any of these during 
the study period.  
43. Current corneal epithelial disease except mild punctate keratopathy 
44. Presence of active renal condition (infection, requirement for dialysis or any other 
condition that could affect participant’s safety). Participants with isolated proteinuria 
resulting from MM are eligible, provided they fulfil criteria given in Table 10 or 
Table 11. 
45. Evidence of active mucosal or internal bleeding. 
46. Any major surgery within the last 4 weeks. 
47. Any serious and/or unstable pre-existing medical, psychiatric disorder, or other 
conditions (including laboratory abnormalities) that could interfere with participant’s 
safety, obtaining informed consent or compliance to the study procedures. 
48. Active infection requiring treatment (antibiotic, antiviral, or antifungal treatment). 
49. Evidence of severe or uncontrolled systemic diseases. 
50. Malignancies other than disease under study are excluded, except for any other 
malignancy from which the participant has been disease-free for more than 2 years 
and, in the opinion of the investigators and Medical Monitor, will not affect the 
evaluation of the effects of this clinical study treatment on the currently targeted 
malignancy (MM). 
51. Evidence of cardiovascular risk including any of the following: 
a. QTcF interval ≥470 msecs (the QT interval values must be corrected for heart rate 
 
by Fridericia’s formula [QTcF]) 
b. Evidence of current clinically significant uncontrolled arrhythmias, including 
 
clinically significant ECG abnormalities such as 2nd degree (Type II) or 3rd 
 
degree atrioventricular (AV) block. 
c. History of myocardial infarction, acute coronary syndromes (including unstable 
 
angina), coronary angioplasty, or stenting or bypass grafting within 6 months of 
 
Screening. 
d. Class III or IV heart failure as defined by the New York Heart Association 
 
functional classification system 
e. Uncontrolled hypertension 
52. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs 
chemically related to GSK2857916 or any of the components of the study treatment. 
53. Pregnant or lactating female or female who are interrupting lactation. 
54. Known human Immunodeficiency virus (HIV) infection. 


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55. Patients with Hepatitis B will be excluded unless the following criteria can be met. 
Serology 
Screening 
During Study Treatment 
 
HBsAb+ and/or 
HBcAb+ 
AND 
 
HBsAg- 
 HBV DNA undetectable 
 Monitoring per protocol 
(Table 4) 
 Antiviral treatment 
instituted if HBV DNA 
becomes detectable 
Note: Participants with positive HBsAb alone due to hepatitis B vaccination can be 
enrolled. 
56. Positive hepatitis C antibody test result or positive hepatitis C ribonucleic acid 
(RNA) test result at screening or within 3 months prior to first dose of study 
treatment. 
Note: Participants with positive hepatitis C antibody due to prior resolved disease 
can only be enrolled, if a confirmatory negative hepatitis C RNA test is obtained. 
Note: Hepatitis RNA testing is optional and participants with negative hepatitis C 
antibody test are not required to also undergo hepatitis C RNA testing. 
57. Current unstable liver or biliary disease per investigator assessment defined by the 
presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or 
gastric varices, persistent jaundice, or cirrhosis. 
Note: Stable chronic liver disease (including Gilbert’s syndrome or asymptomatic 
gallstones) or hepatobiliary involvement of malignancy is acceptable if participant 
otherwise meets entry criteria. 
58. Previously diagnosed with interstitial lung disease or current complication of 
interstitial lung disease. 
Additional Exclusion Criteria for Part 2 Arm A 
59. Intolerant to bortezomib or refractory to bortezomib. 
60. Ongoing Grade 2 or higher peripheral neuropathy or neuropathic pain. 
61. Intolerance or contraindications to herpes zoster prophylaxis. 
Additional Exclusion Criteria for Part 2 Arm B 
62. Prior pomalidomide use. 
63. Intolerance or contraindications to antithrombotic prophylaxis. 
64. Active or history of venous thromboembolism within 3 months prior to first dose of 
study treatment. 
5.3. 
Lifestyle Considerations  
Following lifestyle restrictions applies while the participants are in the study: 
 
Part 1 and Part 2: 


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 
Contact lenses are prohibited while the participant is receiving GSK2857916.  
Contact lens use may be restarted after an ophthalmologist confirms there are no 
other contraindications.  Use of bandage contact lenses is permitted during study 
treatment as directed by the treating eye care specialist. 
 
Part 2 Arm B: 
 
Participants must not donate blood when receiving pomalidomide, during dose 
interruptions, and for 28 days following discontinuation of pomalidomide, as 
transfused blood might be given to a pregnant female whose fetus must not be 
exposed to the drugs. 
No other lifestyle restrictions are required for participants in this study. 
5.4. 
Screen Failures  
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently entered in the study. A minimal set of screen failure information 
is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to 
respond to queries from regulatory authorities. Minimal information includes 
demography, screen failure details, eligibility criteria, and SAEs. 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened. Rescreened participants must be assigned a new unique participant 
number that is different from the initial number. 
6. 
STUDY TREATMENT  
Study treatment is defined as any investigational intervention intended to be administered 
to a study participant according to the study protocol. 
Refer to Table 12, Table 13, and the SRM for further details. 
Table 12 
Study Treatment Administered for Part 1 
Product name: 
GSK2857916  
Dosage form: 
Lyophilized powder, 100 mg/vial in single-use vial for reconstitution  
Unit dose strength(s)/Dose 
Level(s): 
100 mg/vial / 2.5 or 3.4 mg/kg 
Route/ 
Administration/ Duration: 
Delivered as IV solution over 30 min 
Dosing instructions: 
Reconstitute GSK2857916 lyophilized powder 100 mg/vial with water for 
injection before use.   
Manufacturer/ Source of 
Procurement: 
GSK 


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Table 13 
Study Treatments Administered for Part 2 
Study Treatment Name 
GSK2857916 
Arm A and Arm B 
Arm A Standard of Care (21-Day Cycle) 
Arm B Standard of Care (28-Day Cycle) 
Bortezomib 
Dexamethasone 
Pomalidomide 
Dexamethasone 
Dosage Formulation 
Lyophilized powder  
Solution for injection for 
subcutaneous (SC) 
Tablet for oral 
administration 
Capsule for oral 
administration 
Tablet for oral 
administration 
Unit Dose Strength(s) 
100 mg/vial in single-use vial 
for reconstitution  
2.5 mg/mL solution 
4 mg 
1 mg, 4 mg 
4 mg 
Dosage Level(s) 
Arm A 
2.5 mg/kg on Day (D) 1 of 
each cycle, once every 3 
weeks (Q3W) 
Arm B 
2.5 mg/kg on D1 of Cycle (C) 1 
and 1.9 mg/kg on C2D1 and 
beyond, once every 4 weeks 
(Q4W) 
1.3 mg/m2 (SC) on D1, 
D4, D8, and D11, Q3W for 
C1-C8 
20 mg orally on D1, D2, 
D4, D5, D8, D9, D11, and 
D12, Q3W for C1-C8 
4 mg orally daily on 
D1-D21, Q4W 
40 mg orally per day on 
D1, D8, D15, and D22 
Q4W 
Route of Administration  
Intravenous 
SC 
Oral 
Oral 
Oral 
Dosing Instructions 
Reconstitute GSK2857916 
lyophilized powder 100 mg/vial 
with water for injection before 
use 
Refer to labels for dosing 
Refer to labels for dosing 
Refer to labels for dosing 
Refer to labels for dosing 
Manufacturer/ Source of 
Procurement 
GSK 
Refer to Site Reference 
Manual (SRM) 
Refer to SRM 
Refer to SRM 
Refer to SRM 
 


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6.1. 
GSK2857916 Treatments Administered for Part 1  
GSK2857916 is to be administered at a calculated dose of 2.5 mg/kg or 3.4 mg/kg as an 
IV infusion, via an infusion pump on D1 of each cycle over 30 minutes.  Premedication is 
not required prior to infusion unless deemed medically necessary by the investigator, in 
which case it should be administered according to institutional recommendations.  The 
dose to be administered is based on actual body weight calculated at baseline (assessed 
on C1D1 prior to dosing).  However, if the change of body weight is greater than 10%, 
the dose must be recalculated based on the actual body weight at the time of dosing.  
Refer to the SRM for more details on preparation and handling, and administration 
instructions for GSK2857916. 
Administration of GSK2857916 will be documented in the clinic source documents and 
reported in the electronic case report form (eCRF).  The time of start and end of infusion 
will be documented in eCRF. 
Any participant experiencing an IRR must receive appropriate medical treatment.  When 
the participant’s condition is stable, the infusion may be restarted at a slower rate.  For 
details on restarting the GSK2857916 infusion after interruption for IRR, please see 
Section 6.7. 
In general, upon restarting, the infusion rate must be decreased by half at the time the 
infusion was interrupted.  
Participants will be treated until disease progression, until unacceptable toxicity 
(Section 7.1 and Section 7.1.1). 
6.2. 
Treatments Administered for Combination Therapy for 
Part 2)  
6.2.1. 
GSK2857916 with Bortezomib/Dexamethasone (Arm A) 21-day 
Cycle  
The dosing schedule for Arm A is depicted in Figure 3. 
Figure 3 
Summary of Dosing Schedule for Arm A  
 
GSK2857916 
GSK2857916 will be administered IV at the dose of 2.5 mg/kg on D1 of every 21-day 
cycle until disease progression, unacceptable toxicity, or withdrawal of consent.  The 


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dose to be administered is based on actual body weight calculated at baseline (assessed 
on C1D1 prior to dosing).  However, if the change of body weight is greater than 10%, 
the dose should be recalculated based on the actual body weight at the time of dosing.  A 
window of ±3 days is acceptable for administration GSK2857916 after C1D1, but at least 
21 days should elapse between consecutive planned doses of GSK2857916. 
Bortezomib 
Bortezomib 1.3 mg/m2 will be administered subcutaneously (SC) on D1, D4, D8, and 
D11 of every 21-day cycle for a total of 8 cycles.  Bortezomib should be administered 
approximately 1 hour after the GSK2857916 infusion is complete, assuming the 
participant is clinically stable.  In participants who experience an IRR during or after 
GSK2857916 administration, the administration of bortezomib will be delayed until the 
IRR has resolved and the participant is considered clinically stable.  At least 72 hours 
should elapse between consecutive doses of bortezomib. 
Dexamethasone 
Dexamethasone 20 mg (orally) should be administered on D1, D2, D4, D5, D8, D9, D11, 
and D12 (the day of and the day after bortezomib treatment) of every 21-day cycle for a 
total of 8 cycles. 
Dexamethasone should be taken approximately at the same time of each day and may be 
taken at home.  On days where bortezomib administration coincides with administration 
of GSK2857916, dexamethasone should be administered orally 1 to 3 hours prior to the 
infusion of GSK2857916.   
For participants who are unable to retain oral medications due to toxicity, dexamethasone 
can be administered IV. 
Refer to the SRM for further details on preparation, handling, and administration 
contained in package inserts. 
6.2.2. 
GSK2857916 with Pomalidomide/Dexamethasone (Arm B) 28-day 
Cycle  
The dosing schedule for Arm B is depicted in Figure 4. 
Figure 4 
Summary of Dosing Schedule for Arm B  
 


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GSK2857916 
GSK2857916 will be administered IV at the dose of 2.5 mg/kg dose on C1D1 and 
1.9 mg/kg on D1 of C2+ Q4W until disease progression, unacceptable toxicity, or 
withdrawal of consent.  The dose to be administered is based on actual body weight 
calculated at baseline (assessed on C1D1 prior to dosing).  However, if the change of 
body weight is greater than 10%, the dose should be recalculated based on the actual 
body weight at the time of dosing.  A window of ±3 days is acceptable for administration 
of GSK2857916 after C1D1, but at least 28 days should elapse between consecutive 
planned doses of GSK2857916. 
Pomalidomide 
Pomalidomide will be taken orally 4 mg per day on D1 to D21 of 28-day cycles until 
disease progression, unacceptable toxicity, or withdrawal of consent.  On days where 
only pomalidomide and dexamethasone are taken at home, they should be taken in the 
morning approximately at the same time each day. 
Pomalidomide is an analogue of thalidomide, which is known to cause severe 
life-threatening human birth defects.  Because of this potential toxicity and to avoid fatal 
exposure, pomalidomide is only available under a restricted distribution program called 
RevMate®.  Site staff including investigators and participants must comply with the 
requirements of the RevMate® program. 
Dexamethasone 
Dexamethasone will be administered orally at a dose of 40 mg per day on D1, D8, D15, 
and D22 of each 28-day cycle.  For participants who are older than 75 years of age or 
have comorbidities or are intolerant to 40 mg, dexamethasone may be administered at the 
lower dose of 20 mg at the discretion of the investigator.  On days of administration of 
GSK2857916, dexamethasone should be administered orally 1 to 3 hours prior to the 
infusion of GSK2857916.  On days where only pomalidomide and dexamethasone are 
taken at home, they should be taken in the morning approximately at the same time each 
day. 
For participants who are unable to retain oral medications due to toxicity, dexamethasone 
can be administered IV. 
Refer to the SRM for further details on preparation, handling, and administration 
contained in package inserts. 
6.3. 
Preparation/Handling/Storage/Accountability  
65. 
The investigator or designee must confirm appropriate temperature conditions 
have been maintained during transit for all study treatment received and any 
discrepancies are reported and resolved before use of the study treatment. 
66. 
Only participants enrolled in the study may receive study treatment and only 
authorized site staff may supply or administer study treatment. All study 
treatments must be stored in a secure, environmentally controlled, and monitored 


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(manual or automated) area in accordance with the labeled storage conditions 
with access limited to the investigator and authorized site staff. 
67. 
The investigator, institution, or the head of the medical institution (where 
applicable) is responsible for study treatment accountability, reconciliation, and 
record maintenance (i.e., receipt, reconciliation, and final disposition records). 
68. 
Further guidance and information for the final disposition of unused study 
treatment are provided in the SRM or other specified location. 
69. 
Under normal conditions of handling and administration, study treatment is not 
expected to pose significant safety risks to site staff.  Take adequate precautions 
to avoid direct eye or skin contact and the generation of aerosols or mists. In the 
case of unintentional occupational exposure notify the monitor, Medical Monitor 
and/or GSK study contact. 
70. 
A Material Safety Data Sheet (MSDS)/equivalent document describing 
occupational hazards and recommended handling precautions either will be 
provided to the investigator, where this is required by local laws, or is available 
upon request from GSK. 
6.4. 
Measures to Minimize Bias: Randomization and Blinding  
This is an open-label study; GSK2857916 will be administered based on actual body 
weight. 
6.5. 
Study Treatment Compliance  
Participants will receive study treatment at the site directly from the investigator or 
designee, under medical supervision.  The date and time of each dose administered in the 
study site will be recorded in the source documents and reported in the eCRF.  The dose 
of study treatment and study participant identification will be confirmed at the time of 
dosing by a member of the study site staff other than the person administering the study 
treatment and documented in source. 
When participants self-administer oral study treatment(s) at home, dosing will be 
recorded in the Participant’s Study Medication Diary.  The entries in the Diary will be 
assessed through querying the participant during the site visits and documented in the 
source documents and eCRF.  A record of the number of doses dispensed to and taken by 
each participant must be maintained and reconciled with study treatment and compliance 
records.  Treatment start and stop dates, including dates for treatment delays and/or dose 
reductions will also be recorded in the eCRF. 
6.6. 
Concomitant Therapy  
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving at the time of 
enrollment or receives during the study must be recorded along with: 
 
reason for use 
 
dates of administration including start and end dates 


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 
dosage information including dose and frequency 
The Medical Monitor should be contacted if there are any questions regarding 
concomitant or prior therapy. 
Participants will be instructed to inform the investigator prior to starting any new 
medications from the time of first dose of study treatment until the end of the study.  
Concomitant medications administered after the end of treatment (EOT) visit should be 
recorded for SAEs/AESIs.  Any concomitant medication(s), including non-prescription 
medication(s) and herbal product(s), taken during the study will be recorded in the eCRF.  
Additionally, a complete list of all prior anti-myeloma therapies will be recorded in the 
eCRF.  Please see the SRM for the list of permitted/prohibited medications. 
6.6.1. 
Permitted Medications  
Participants should receive full supportive care during the study, including transfusions of 
blood products, growth factors, and treatment with antibiotics, anti-emetics, antidiarrheal, 
and analgesics, as appropriate.   
 
While the participants are receiving treatment with pomalidomide, 
thromboprophylaxis is recommended and the choice of regimen should be based on 
an assessment of the participant’s underlying risks, in accordance with local 
prescribing information. 
 
Herpes zoster prophylaxis is recommended in accordance with local prescribing 
information in participants being treated with bortezomib. 
 
Concomitant therapy with bisphosphonates is allowed and recommended.   
 
Concomitant prophylactic treatment for tumor lysis syndrome (according to local 
standards) in participants with high tumor load should be considered. 
Participants may receive local irradiation for pain or stability control.  In Japan, it is not 
approved to use growth factor products (except for granulocyte-colony stimulating factor) 
for neutropenia due to cancer chemotherapy and erythropoietin products for anemia due 
to cancer chemotherapy. 
6.6.2. 
Prohibited Medications  
Chronic treatment with oral steroids other than part of the study treatment is prohibited 
while the participant is on study, unless for treatment of acute complications related to 
study treatment, or pre-medication prior to GSK2857916 infusion.  Steroids may be used 
to treat IRRs, and acute exacerbations of chronic disease (up to 7 days).  Inhaled steroids 
are allowed for management of asthma or chronic obstructive pulmonary disease 
exacerbations.  Chronic low dose replacement therapy (less than or equal to 10 mg 
prednisolone) is allowed in participants with adrenal insufficiency. 
Elimination pathways for GSK2587916 or cys-mcMMAF in humans have not been 
characterized in humans.  Cys-mcMMAF was not an inhibitor, an inducer or a good 
substrate of CYP450 enzymes in vitro.  However, in vitro, cys-mcMMAF was shown to 
be a substrate of P-gp, and OATP (OATP1B1 and OATP1B3) transporters.  Concomitant 


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administration of strong P-gp inhibitors and strong OATP1B1 and OATP1B3 inhibitors 
with GSK2857916 should be avoided unless considered medically necessary.  Please see 
the SRM for a list of relevant P-gp inhibitors and OATP1B1 and OATP1B3 inhibitors. 
Other prohibited therapies include: 
 
Growth factor products: prohibited from 14 days prior to clinical laboratory test 
(hematology) at Screening to first dose and prohibited to use for primary 
prophylaxis during DLT observation period. 
 
Blood products: prohibited from 7 days prior to clinical laboratory test 
(hematology) at Screening to first dose. 
 
Plasmapheresis: prohibited from 7 days prior to first dose through the end of 
study. 
 
Any other approved or investigational anti-myeloma therapy not specified in this 
protocol (including but not limited to immunomodulatory and antineoplastic 
drugs or proteasome inhibitors). This is inclusive of all medications with activity 
against multiple myeloma and medications used for other indications that have 
anti-myeloma properties. 
 
Investigational agents other than GSK2857916. 
 
In Part 2, administration of live or live-attenuated vaccines are contraindicated 
30 days prior to the first dose of study treatment and while on study.  Use of live 
or live-attenuated vaccines is further contraindicated for at least 70 days 
following the last dose of GSK2857916.  Killed or inactivated vaccines may be 
administered; however, the response to such vaccines cannot be predicted. 
Bortezomib is a substrate of CYP450 enzyme 3A4, 2C19 and 1A2.  Caution should be 
exercised when bortezomib is combined with CYP3A4 or CYP2C19 substrates.  
Participants should be closely monitored when given bortezomib in combination with 
potent CYP3A4 inhibitors.  Co-administration with strong CYP3A4 inhibitors can 
increase bortezomib exposure by 35%.  If bortezomib must be given in combination with 
a strong CYP3A4 inhibitor (e.g., ketoconazole, ritonavir), monitor participants for signs 
of bortezomib toxicity and consider a bortezomib dose reduction.  Co-administration with 
strong CYP3A4 inducers may decrease bortezomib exposure by 45% or more, which 
may reduce bortezomib efficacy.  Strong CYP3A4 inducers are therefore not 
recommended in combination with bortezomib.  St. John’s Wort (Hypericum perforatum) 
may decrease bortezomib exposure unpredictably and should be avoided. 
Pomalidomide clearance includes hydrolysis and CYP450-mediated hydroxylation.  In 
vitro pomalidomide was neither an inducer nor inhibitor of CYP450, nor an inhibitor of 
transporter proteins P-gp.  Oxidative metabolism of pomalidomide was predominantly 
mediated by CYP1A2 and CYP3A4, and pomalidomide was shown to be a P-gp 
substrate.  Co-administration of pomalidomide with fluvoxamine (CYP1A2 inhibitor) in 
the presence of ketoconazole approximately doubled pomalidomide exposure.  Thus, 
concomitant use of strong CYP1A2 inhibitors with pomalidomide should be avoided.  If 
a strong CYP1A2 inhibitor must be used, reduce pomalidomide dose by 50%. 


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For further information see the package inserts included in the SRM [Pomalyst, 2019; 
VELCADE, 2019]. 
6.6.3. 
Prohibited Device(s)  
Contact lenses are prohibited while the participant is on study. 
6.7. 
Dose Modification and Delay  
6.7.1. 
Dose Modification and Delay for Part 1  
After C1, participants may have their dose delayed or reduced for toxicities according to 
the guidance. 
See Table 15 for dose modifications guidelines for GSK2857916-related AEs and 
Table 16 for guidelines for drug-related AEs. 
See Table 17 for dose modification guidelines for cornea-related AEs associated with 
GSK2857916. 
Permitted dose reductions for GSK2857916 are shown in Table 14. 
Table 14 
Permitted Dose Reductions 
Starting dose level 
1st reduction 
(25% reduction of original dose) 
2nd reduction 
(Additional 25% reduction of  
reduced dose) 
2.5 mg/kg 
1.92 mg/kg 
-- 
3.4 mg/kg 
2.5 mg/kg 
1.92 mg/kg 
 
Dose reduction up to 1.92 mg/kg is permitted (up to 2 dose reductions for 
3.4 mg/kg and up to 1 dose reduction for 2.5 mg/kg).  
 
25% dose reduction is defined as de-escalation to 1 lower dose level. 
 
If the participant cannot tolerate the drug after the allowed dose reductions, he or 
she must be withdrawn from the study for lack of tolerability. 
 
In case of full resolution of symptoms which lead to dose reduction, further 
treatment at the previous dose may be considered by the investigator. 
Dosing delays are permitted in the case of medical/surgical events or for logistical 
reasons not related to study therapy (e.g., elective surgery, unrelated medical events, 
participant vacation, and/or holidays, but not for participants’ decision to delay 
treatment).  If a dose is delayed, the participant should wait for the next scheduled dose to 
resume treatment. The reason for any dose delay must be documented in the participant's 
eCRF and site record. 
Resuming treatment with GSK2857916 will be possible with or without dose reduction 
after the toxicity has resolved to Grade 1 or less.  


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Table 15 
Dose Modification Guidelines for GSK2857916-Related Adverse 
Events for Part 1 
Toxicity 
Grade/description 
of toxicity 
Recommendations for GSK2857916 
Elevated serum creatinine 
which cannot be explained by 
concomitant sepsis, tumor 
lysis syndrome, other severe 
condition with fever, or 
dehydration 
If absolute serum 
creatinine 
increases from 
baseline by 
>0.5 mg/dL 
 
Repeat serum creatinine or eGFR within 48 hours 
 
If confirmed: withhold therapy, institute treatment and 
monitoring as clinically indicated, and follow for 
resolution 
 
Discuss any further dosing with Medical Monitor 
Serum creatinine >Grade 3 
>3.0 mg/dL from 
baseline 
or 
3.0-6.0xULN 
 
Provide appropriate medical treatment. 
 
Permanently discontinue treatment with GSK2857916  
Spot urine (albumin / 
creatinine ratios) 
>2000 mg/g 
(or 224 mg/mmol) 
 
Re-test (at least 7 days apart) 
 
If not confirmed, continue GSK2857916 at 100% 
dose 
 
If confirmed on re-test and no clear evidence of 
disease progression 
o 
Interrupt treatment with GSK2857916 
o 
Repeat testing within 4 weeks 
i. 
If spot urine <2000 mg/g (224 mg/mmol), 
may restart GSK2857916 with 25% dose 
reduction 
ii. 
If spot urine remains >2000 mg/g 
(224 mg/mmol) after 4 weeks, 
permanently discontinue GSK2857916 
and withdraw participant from study; 
provide treatment as clinically indicated 
and follow for resolutiona 
Thrombocytopenia  
(on days of dosing)  
3 
 
No bleeding: continue treatment with 25% dose 
reduction.  Consider reverting to previous dose once 
thrombocytopenia recovered to G2 or less 
 
With bleeding: withhold the dose, continue treatment 
after recovery with 25% dose reduction 
Thrombocytopenia 
(On days of dosing) 
4 
 
Withhold the dose.  Consider restarting with 25% 
dose reduction if recovered, or transfused to G3 
only if there is no active bleeding at time of treatment 
re-start 
 
If thrombocytopenia is considered disease related, is 
not accompanied by bleeding, and recovers with 
transfusion to >25x109/L continuing treatment at 25% 
dose reduction or additional 25% dose reduction of 
reduced dose (i.e. up to 1.92 mg/kg) may be 
considered after discussion with the Medical Monitor 
Febrile neutropenia 
3-4 
(defined as: single 
temp of >38.3oC, 
or sustained ≥38oC 
for >1 hr AND ANC 
<1000/mm3 
 
Withhold the dose 
 
Implement treatment with antibiotics, antivirals and 
antifungals, as clinically indicated, consider growth 
factors 
 
Continue treatment after resolution.  Consider 25% 
dose reduction of GSK2857916, if neutropenia was 
drug related 


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Toxicity 
Grade/description 
of toxicity 
Recommendations for GSK2857916 
Infusion-Related Reactionb 
2 
 
Stop the infusion, provide medical treatment and 
continue at half the original infusion rate after 
resolution to Grade 0-1 
Infusion-Related Reactionb 
3 
 
Further treatment with GSK2857916 needs to be 
discussed with Medical Monitor.  Continuation only 
allowed after recovery to Grade 1 and with pre-
medication, and extension of infusion time to 2-4 
hours.  Any future infusion needs to be pre-medicated 
4 
 
Permanently discontinue 
Pneumonitis 
2 
 
Continue treatment when toxicity resolves to Grade 0-
1 
Grade 3-4 
 
Permanently discontinue 
a. 
Medical Monitor may consult GSK’s nephrology panel about plans to continue therapy. 
b. 
If symptoms resolve within one hour of stopping infusion, the infusion may be restarted at 50% of the original 
infusion rate (e.g., from 100 mL/hr to 50 mL/hr).  Otherwise dosing will be held until symptoms resolve and the 
participant must be pre-medicated for the next scheduled dose. 
Table 16 
General Dose Modification and Management Guidelines for 
Drug-related Adverse Events Not Otherwise Specifieda for Part 1 and 
Part 2 
Severity 
Management 
Follow-up 
Grade 1 
 
Administer symptomatic 
treatment as appropriate 
 
Continue study treatmenta 
 
Provide close follow-up to evaluate for increased 
severity, no dose modification necessary 
Grade 2 
 
Administer symptomatic 
treatment 
 
Investigate etiology 
 
Consider consulting 
subspecialist, and/or 
diagnostic procedure 
Symptoms resolved in ≤7 days: 
Continue after resolution at the current dose 
Symptoms ongoing >7 days or worsening: 
o Delay study drugb, or consider dose reduction by 
25% (or consider at the same dose level for Part 2 
Arm B) If recovery takes >3 weeks- consult 
Medical Monitor  
 
If symptoms continue or worsen to Grade 3-4, see 
below 
Grade 3 
 
Provide appropriate 
medical treatment  
 
Consider consulting 
subspecialist 
Delay treatment till recovery to Grade 1 or less.  Consider 
dose reduction (or consider at the same dose level for Part 2 
Arm B).  Consider consultation with Medical Monitor. 
Exceptions: Participants who develop Grade 3 toxicities 
which respond to standard treatment and resolve to ≤Grade 
1 within 48 hours may continue treatment at scheduled or 
reduced dose  
Grade 4 
 
Provide appropriate 
medical treatment 
 
Consider Consulting 
subspecialist 
 
Discuss with 
Sponsor/Medical Monitor 
Interrupt treatment.  Further treatment with GSK2857916 
only allowed on individual basis if in the discussion with 
Medical Monitor it is agreed that benefits outweigh the risks 
for a given participant 
c. 
Treatment-related decisions can be made based on local laboratory results if central results are not available or 
delayed. 
d. 
In case a dose is delayed, the participant should wait for the next scheduled dose to resume treatment. 
 


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Table 17 
Dose Modification Guidelines for GSK2857916 Treatment-Related 
Corneal Events for Part 1 
 
Grade 1 per 
GSK Scalea 
Grade 2 per GSK 
Scalea 
Grade 3 per GSK 
Scalea 
Grade 4 per GSK 
Scalea 
GSK2857916 
Dosing 
Actions 
Continue 
treatment with 
current dose of 
GSK2857916. 
If either ophthalmic 
exam findings or visual 
acuity findings are 
Grade 1, continue 
dosing with 
GSK2857916 at current 
dose. 
Hold GSK2857916. 
 
Upon 
improvement of 
either visual acuity 
or ophthalmic 
exam findings to 
Grade 1 or 
baseline, resume 
with 25% dose 
reduction*. 
(* for participants 
receiving 1.92 mg/kg, 
dose continue at same 
dose) 
Stop treatment with 
GSK2857916. 
If visual acuity and 
exam findings are both 
Grade 2, HOLD 
GSK2857916. 
 
Upon 
improvement of 
either visual acuity 
or ophthalmic 
examination 
findings to 
Grade 1 or 
baseline, resume 
with current dose. 
In case of recurring 
Grade 3 events, 
consider consulting 
GSK. 
Additional topical 
treatment may be 
prescribed as 
recommended by 
ophthalmologist. 
Treatment re-start may 
be possible after 
discussion and 
agreement between 
the treating 
ophthalmologist, 
treating physician, and 
possible discussions 
with GSK. 
Corneal 
Management 
Care 
Regardless of 
Grade 
Preservative-free Artificial Tears: 
 
Increase to 1 drop as frequently as every 2 hours, as needed. 
Cooling Eye Masks: 
 
At the start of each infusion, participants may apply cooling eye masks to their eyes for 
approximately 1 hour or as long as tolerated. 
Steroid Eye Drops: 
 
Corticosteroid eye drops are not required but can be used if clinically indicated per 
discretion of an eye-care specialist. Allow at least 5-10 minutes between administration 
of artificial tears and steroid eye drops (if administered). 
e. 
See Appendix 7 for corneal event grading scale 
 
6.7.2. 
Dose Modification and Delay for Part 2 Arm A  
Dose delays and reductions are permitted throughout the study as described below. 
After Cycle 1 Day 1, dose modifications may be made for individual participants based 
on safety findings. 


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Dosing delays are also permitted for medical/surgical events or logistical reasons not 
related to study therapy (e.g., elective surgery, unrelated medical events, participant 
vacation, and/or holidays) but not for participant’s decision to delay treatment. 
6.7.2.1. 
GSK2857916  
The dose allowed for GSK2857916 may be reduced once from the starting dose (Dose 
Level -1) (Table 18).  Participants not able to tolerate Dose Level -1 will permanently 
discontinue GSK2857916 treatment due to unacceptable toxicity.  Detailed guidance for 
dose modifications are shown in Table 16, Table 19, and Table 20.  
In case of full resolution of symptoms which lead to dose reduction, further treatment at 
the previous dose may be considered by the investigator. 
Table 18 
Dose Levels GSK2857916 for Part 2 Arm A 
Dose Level 
GSK2857916 Dose 
Starting Dose 
2.5 mg/kg intravenously (IV) once every 3 weeks (Q3W) 
Dose Level -1  
1.9 mg/kg IV Q3W  
 
Table 19 
Dose Modification Guidelines for Adverse Events Associated with 
GSK2857916 for Part 2 Arm A 
Toxicity 
Grade/Symptoms 
Recommendations  
Serum creatinine elevation 
which cannot be explained 
by concomitant sepsis, 
tumor lysis syndrome, 
other severe condition with 
fever or dehydration 
If absolute serum 
creatinine increases 
from baseline of 
>0.5 mg/dL 
Repeat within 48 hours 
 
If confirmed: withhold therapy, initiate treatment and 
monitoring as clinically indicated, and follow for 
resolution. 
Discuss any further dosing with Medical Monitora 
Serum creatinine >Grade 3 
>3.0 mg/dL from 
baseline 
or 
3.0-6.0 × ULN 
 
Provide appropriate medical treatment 
 
Permanently discontinue treatment with 
GSK2857916 
Spot urine (albumin / 
creatinine ratios) 
>2000 mg/g 
(224 mg/mmol) 
 
Re-test (at least 7 days apart) 
 
If not confirmed, continue GSK2857916 at pre-held dose 
 
If confirmed on re-test and no clear evidence of disease 
progression: 
o 
Interrupt treatment with GSK2857916 
o 
Repeat testing within 4 weeks 
o If spot urine ≤2000 mg/g (224 mg/mmol), may restart 
GSK2857916 with 1 dose level reduction 


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Toxicity 
Grade/Symptoms 
Recommendations  
o If spot urine remains >2000 mg/g (224 mg/mmol) 
after 4 weeks, permanently discontinue 
GSK2857916 and withdraw participant from study; 
provide treatment as clinically indicated and follow 
for resolutiona. 
Thrombocytopenia (on 
days of dosing)  
Graded according to 
National Cancer Institute-
Common Terminology 
Criteria for Adverse Events 
(NCI-CTCAE) criteria 
Grade 3 
 
No bleeding: continue treatment with 1 dose level 
reduction. Consider reverting to previous dose once 
thrombocytopenia recovered to Grade 2, or less. 
 
With bleeding: withhold the dose, continue treatment 
after recovery with 1 dose level reduction. 
 
Consider additional supportive treatment (e.g., 
transfusion), as clinically indicated and per local practice. 
Grade 4 
 
Withhold the dose.  Consider restarting with 1 dose level 
reduction if recovered, or transfused to ≤Grade 3 only if 
there is no active bleeding at time of treatment restart 
 
If thrombocytopenia is considered disease related, is not 
accompanied by bleeding, and recovers with transfusion 
to >25x109/L, continuing treatment with dose reduction 
may be considered after discussion with the Medical 
Monitor 
Neutropenia 
Graded according to NCI-
CTCAE criteria 
≥Grade 3 (Defined as 
absolute neutrophil 
count [ANC] <1.0x109/L) 
 
If noted on Day (D) 1 of any cycle, withhold GSK2857916 
dose. 
 
Resume GSK2857916 at pre-held dose once 
neutropenia recovers to ≤Grade 2 (ANC ≥1.0x109/L) on 
D1 of a subsequent cycle. 
 
Prophylactic antibiotics, per physician discretion and 
local institutional guidance.  Consider growth factors.  
 
Local guidance must be followed for hematological 
monitoring if more conservative than the protocol 
schedule of activities specifications.  
 
In cases of frequent recurrent neutropenia (ANC 
<1.0x109/L), consider dose reduction of GSK2857916. 
Febrile neutropenia 
Graded according to 
NCI-CTCAE criteria 
Grade 3-4 (Defined as: 
single temperature of 
>38.3°C, or sustained 
≥38°C for >1 hr AND 
ANC <1.0x109/L) 
 
Withhold GSK2857916 and immediately hospitalize 
participant with appropriate management, per local 
institutional guidance. 
 
Consider additional supportive treatment per local 
practice (e.g., growth factors). 
 
Upon recovery, consider dose reduction of GSK2857916, 
if neutropenia was drug-related. 
Infusion-Related Reactionb 
Grade 2 
 
Stop the infusion, provide medical treatment and 
continue at a reduced rate after resolution to Grade 0-1 


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Toxicity 
Grade/Symptoms 
Recommendations  
Grade 3 
 
Further treatment with GSK2857916 needs to be 
discussed with Medical Monitor.  Continuation only 
allowed after recovery to ≤Grade 1 and with 
premedication, and extension of infusion time to 
2-4 hours.  Any future infusion needs to be 
premedicated. 
Grade 4 
 
Permanently discontinue 
Pneumonitis 
Grade 2 
 
Withhold treatment with GSK2857916  
 
Upon recovery, restart treatment with 1 dose level 
reduction. 
 
If participant is already at the lowest dose level 
(1.9 mg/kg), then rechallenge with the same dose must 
be discussed with the Medical Monitor  
Grade 3-4 
 
Permanently discontinue treatment with GSK2857916  
f. 
Medical Monitor may consult GSK’s nephrology panel about plans to continue therapy. 
g. 
If symptoms resolve within 1 hour of stopping infusion, the infusion may be restarted at 1 dose level reduction of 
the original infusion rate (e.g., from 100 mL/h to 50 mL/h).  Otherwise, dosing will be held until symptoms resolve 
and the participant must be pre-medicated for the next scheduled dose. 
 


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Table 20 
Dose Modification Guidelines for GSK2857916 Treatment-Related 
Corneal Events for Part 2 
Grade per GSK scale 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Recommended 
Dosage 
Modificationsa 
Continue treatment 
at current dose. 
Withhold 
GSK2857916 until 
improvement in 
either corneal 
examination 
findings or 
changes in BCVA 
to Grade 1 or 
better and resume 
at same dose. 
Withhold 
GSK2857916 until 
improvement in 
either corneal 
examination 
findings or 
changes in BCVA 
to Grade 1 or 
better and resume 
at reduced dose (1 
level)b. 
 
Consider re-
escalating after at 
least 2 ophthalmic 
assessments post 
treatment re-
initiation, for events 
that do not worsen 
after resuming at 
lower dose and 
following 
benefit/risk 
assessment and 
discussion with the 
Sponsor. 
Permanently 
discontinue 
GSK2857916.  
 
Patient may be re-
challenged on a 
case-by-case basis 
at a reduced dose 
after improvement 
and following 
benefit/risk 
assessment and 
discussion 
between the eye 
care specialist, the 
investigator, and 
the Sponsor.  
BCVA = best corrected visual acuity 
h. 
Dose modification should be based on the most severe grade. If eyes differ in severity, dose modification 
guideline should be applied based on the more severe eye. 
i. 
If already on reduced dose (1.9 mg/kg), participant should resume treatment at that dose. 
 
6.7.2.2. 
Bortezomib  
Detailed guidance for bortezomib dose modifications is shown in Table 21 and Table 22. 
If the decision is made to permanently discontinue bortezomib, but GSK2857916 
continues, a participant may remain in the study and continue treatments and assessments 
as described in the SoA (Section 1.3).  
Dose adjustments should be based on the highest grade of toxicity that is attributed to 
bortezomib.  Bortezomib therapy should be withheld at the onset of any Grade 3 
non-hematological or Grade 4 hematological toxicities excluding neuropathy.  Once the 
symptoms of the toxicity have resolved, bortezomib therapy may be reinitiated at a 
reduced dose per approved labeling, as described in Table 21. 


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Table 21 
Dose Levels for Bortezomib 
Dose Level 
Bortezomib Dose 
Starting Dose 
1.3 mg/m2 
Dose Level -1  
1.0 mg/m2 
Dose Level -2 
0.7 mg/m2 
Dose Level -3 
Discontinue bortezomib 
 
Table 22 
Dose Modification Guidelines for Hematologic and Other Toxicities 
Associated with Bortezomib 
Toxicity 
Grade 
Recommendations 
Hematological toxicity 
≥Grade 4 
 
Withhold bortezomib therapy until symptoms of toxicity 
have resolved. 
 
Bortezomib may be reinitiated with 1 dose level 
reduction (from 1.3 mg/m2 to 1 mg/m2, or from 1 mg/m2 
to 0.7 mg/m2). 
Non-hematological 
toxicities (excluding 
peripheral neuropathy) 
≥Grade 3 
 
Withhold bortezomib therapy until symptoms of toxicity 
have resolved. Then, bortezomib may be reinitiated 
with a 1 dose level reduction (from 1.3 mg/m2 to 1 
mg/m2, or from 1 mg/m2 to 0.7 mg/m2). 
 
For bortezomib-related neuropathic pain and/or 
peripheral neuropathy, hold or modify bortezomib as 
outlined below and in the package inserts included in 
the Site Reference Manual. 
Peripheral neuropathy 
Grade 1 
 
Defined as clinical or diagnostic observations only 
 
Grade 1 asymptomatic, without pain or loss of function 
– No action needed 
 
Grade 1 with pain: 1 dose level reduction (from 
1.3 mg/m2 to 1 mg/m2, or from 1 mg/m2 to 0.7 mg/m2) 
Grade 2 
 
Defined as moderate symptoms; limiting instrumental 
Activities of Daily Living (ADL)a 
 
Grade 2 with no pain: 1 dose level reduction (from 
1.3 mg/m2 to 1 mg/m2, or from 1 mg/m2 to 0.7 mg/m2) 
 
Grade 2 with pain: withhold bortezomib therapy until 
toxicity resolves.  When toxicity resolves reinitiate with 
a reduced dose of bortezomib at 0.7 mg/m2 once per 
week 
Grade 3 
 
Defined as severe symptoms; limiting self-care ADLb 


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 
Grade 3: withhold bortezomib therapy until toxicity 
resolves. When toxicity resolves reinitiate with a 
reduced dose of bortezomib at 0.7 mg/m2 once per 
week 
Grade 4 
 
Defined as life-threatening consequences; urgent 
intervention indicated 
 
Discontinue bortezomib 
a. 
Instrumental ADL: refers to preparing meals, shopping for groceries or clothes, using telephone, managing 
money etc. 
b. 
Self-care ADL: refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden. 
 
6.7.2.3. 
Dexamethasone  
Starting dose of dexamethasone may be reduced to 10 mg for participants older than 
75 years of age, who have a body mass index (BMI) of less than 18.5, who had previous 
unacceptable side effects associated with glucocorticoid therapy, or who are unable to 
tolerate the starting dose (Table 23). 
For participants with contraindications to the starting dose regimen of dexamethasone in 
combination with bortezomib, or who are intolerant to this regimen, the dose of 
dexamethasone can be reduced dose level -1.  If dose level -1 is not tolerated, the 
dexamethasone dose can be reduced by a further 50%.  If this is also not tolerated, 
dexamethasone should be discontinued. 
If bortezomib dosing is delayed or discontinued, dexamethasone dosing could continue 
per investigator discretion and local institutional guidelines. 
Dose modification guidelines are described in Table 24 for dexamethasone-related AEs. 
Table 23 
Permitted Dose Reductions for Dexamethasone for Part 2 Arm A 
Dose Level 
≤ 75 years of age 
> 75 years of age, BMI ≤ 18.5 Kg/m2 
Starting dose 
20 mg 
10 mg 
Dose level -1   
12 mg 
6 mg 
Dose level -2*  
8 mg 
4 mg 
*Dexamethasone could be reduced further than dose level -2 per Investigator discretion. 
 


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Table 24 
Dose Modifications Guidelines for Dexamethasone-Related Adverse 
Events for Part 2 
Toxicity 
Dose Modification 
Dyspepsia + Grade 1-2 
 
Dyspepsia ≥ Grade 3 
Maintain dose and treat with histamine (H2) blockers or 
equivalent.  Decrease by 1 dose level if symptoms persist.  
Interrupt dose until symptoms are controlled.  Add H2 blocker 
or equivalent and decrease 1 dose level when dose restarted.  
Edema ≥ Grade 3 
Use diuretics as needed and decrease dose by 1 dose level.  
Confusion or mood alteration ≥ Grade 2 
Interrupt dose until symptoms resolve.  When dose restarted, 
decrease dose by 1 dose level. 
Muscle weakness ≥ Grade 2 
Interrupt dose until muscle weakness ≤Grade 1.  Restart with 
dose decreased by 1 level. 
Hyperglycemia ≥ Grade 3 
Decrease dose by 1 dose level.  Treat with insulin or oral 
hypoglycemic agents as needed.  
Acute pancreatitis  
Discontinue participant from dexamethasone treatment 
regimen.  
Other ≥ Grade 3 dexamethasone-related adverse 
events  
Stop dexamethasone dosing until adverse event resolves to 
≤Grade 2.  Resume with dose reduced by 1 level.  
 
6.7.2.4. 
Guidance on Dose Delays  
Table 25 provides guidance on dose delays for Part 2 Arm A.  
In any dosing delay scenario, Q3W assessments should continue to be carried out as 
described in the SoA.  For treatment delays within the treatment window, subsequent 
treatment dates will not be adjusted. 


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Table 25 
Dose Delays for Part 2 Arm A 
Scenario 
Actions for GSK2857916 
Actions for Bortezomib 
1. Delay of only 
GSK2857916 
After Cycle (C) 1, a window of 3 days is 
acceptable for GSK2857916 dosing.  
Outside this window, treatment should be 
given on Day (D) 1 of the next planned 
cycle. 
Continue bortezomib according to the 
regimen outlined in the schedule of 
activities (SoA), until completion of 8 full or 
truncated cycles of bortezomib. 
2. Delay of only 
bortezomib 
Continue GSK2857916 according to the 
regimen outlined in the SoA. 
Bortezomib should be administered on the 
planned treatment day.  If treatment 
cannot be administered as planned, when 
a participant is ready to resume treatment, 
bortezomib may be restarted at the 
appropriate point in the planned dosing 
regimen, e.g., if the participant is unable to 
receive bortezomib on D1 and D4 of a 
given cycle, treatment could resume on 
D8 or D11, and missed D1 and D4 doses 
will not be made up. 
3. Delay of both 
GSK2857916 and 
bortezomib >21 days 
(C1-C8) 
Bortezomib can be resumed at the appropriate point in the cycle, e.g., in C1-C8, if the 
participant is unable to receive bortezomib on D1 and D4, resume treatment with 
bortezomib on D8 or D11.  
GSK2857916 should be administered on D1 of the next planned cycle. 
Visits and assessments should continue to occur as specified in the SoA until treatment 
is restarted. 
4. Delay of both 
GSK2857916 and 
bortezomib <21 days 
(C1-C8) 
Follow the guidance as outlined in 
Scenario 1 above. 
Follow the guidance as outlined in 
Scenario 2 above. 
 
6.7.3. 
Dose Modification and Delay for Part 2 Arm B  
6.7.3.1. 
GSK2857916  
After C1, participants may have their dose delayed or reduced for toxicities according to 
the recommendations. 
See Table 26 for dose modification guidelines for GSK2857916-related AEs, Table 16 
for guidelines for drug-related otherwise specified AEs, and Table 20 for dose 
modification guidelines for corneal-related AEs associated with GSK2857916. 
 
GSK2857916 will be administered at 2.5 mg/kg on C1D1 and then followed at 
1.9 mg/kg on D1 of C2+ Q4W. 
 
For GSK2857916, no dose reductions, except for dose delays and interruptions, will 
be allowed. 


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 
If the participant cannot tolerate the drug after the allowed dose level of 
GSK2857916, the participant can delay or interrupt GSK2857916 treatment and can 
continue Pom/Dex therapy. 
 
In case of full resolution of symptoms which lead to dose delay or interruption, 
further treatment at the same dose level may be considered by the investigator. 
Dosing delays are permitted in the case of medical/surgical events or for logistical 
reasons not related to study treatment (e.g., elective surgery, unrelated medical events, 
participant vacation, and/or holidays), but not simply for participants’ decision to delay 
treatment.  For dose delays or interruptions lasting more than 21 days the Medical 
Monitor should be contacted to discuss restarting treatment. 
The reason for any dose delay must be documented in the participant’s eCRF and clinic 
record.  Where safety findings cannot be ascribed solely to 1 study treatment, follow the 
guidance provided in Table 16. 
Resuming treatment with GSK2857916 will be possible without dose reduction after the 
toxicity has resolved to Grade 2 or less. 


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Table 26 
Dose Modifications Guidelines for GSK2857916 Treatment-Related Adverse Events for Part 2 Arm B 
Toxicity 
Grade/Symptoms 
Recommendations 
Elevated serum creatinine that cannot be 
explained by concomitant sepsis, tumor lysis 
syndrome, other severe condition with fever, or 
dehydration 
If absolute serum creatinine 
increases from baseline by 
>0.5 mg/dL 
 
Repeat within 48 hours. 
 
If confirmed: withhold therapy, institute treatment and monitoring as clinically indicated, 
and follow for resolution. 
 
Discuss any further dosing with Medical Monitora. 
Serum creatinine >Grade 3 
>3.0 mg/dL from baseline  
or 
3.0-6.0 x ULN 
 
Provide appropriate medical treatment. 
 
Permanently discontinue treatment with GSK2857916. 
Spot urine (albumin/creatinine ratios) 
>2000 mg/g 
(or 224 mg/mmol) 
Re-test (at least 7 days apart) 
 
If not confirmed, continue GSK2857916 at pre-held dose.  
 
If confirmed on re-test and no clear evidence of disease progression 
o 
Interrupt treatment with GSK2857916. 
o 
Repeat testing within 4 weeks. 
o If spot urine <2000 mg/g (224 mg/mmol), may restart GSK2857916 at same dose 
level. 
o If spot urine remains >2000 mg/g (224 mg/mmol) after 4 weeks, permanently 
discontinue GSK2857916 and withdraw participant from study; provide treatment 
as clinically indicated and follow for resolutiona. 


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Toxicity 
Grade/Symptoms 
Recommendations 
Thrombocytopenia (on days of dosing)  
 
Graded according to National Cancer Institute-
Common Terminology Criteria for Adverse 
Events (NCI-CTCAE) criteria 
Grade 3 
 
No bleeding: continue treatment with at the same dose level. 
 
With bleeding: withhold the dose, continue treatment after recovery at the same dose 
level. 
 
Consider additional supportive treatment (e.g., transfusion), as clinically indicated and 
per local practice. 
Grade 4 
 
Withhold the dose.  Consider restarting at the same dose level if recovered, or 
transfused to ≤Grade 3 only if there is no active bleeding at time of treatment restart. 
 
If thrombocytopenia is considered disease related, is not accompanied by bleeding, 
and recovers with transfusion to >25x109/L continuing treatment at the same dose level 
may be considered after discussion with the Medical Monitor. 
Neutropenia 
Graded according to NCI-CTCAE criteria 
Grade ≥3 (Defined as absolute 
neutrophil count [ANC] 
<1.0x109/L) 
 
If noted on Day (D) 1 of any cycle, withhold GSK2857916 dose. 
 
Resume GSK2857916 at pre-held dose once neutropenia recovers to ≤Grade 2 (ANC 
≥1.0x109/L) on D1 of the subsequent cycle. 
 
Prophylactic antibiotics, per physician discretion and local institutional guidance.  
Consider growth factors. 
 
Local guidance must be followed for hematological monitoring, if more conservative 
than the protocol schedule of activities specifications. 
 
In cases of frequent recurrent neutropenia (ANC <1.0x109/L), consider at the same 
dose level of GSK2857916. 


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Toxicity 
Grade/Symptoms 
Recommendations 
Febrile neutropenia 
Graded according to NCI-CTCAE criteria 
Grade 3-4 (Defined as: single 
temperature of >38.3°C, or 
sustained ≥38°C for >1 hr AND 
ANC <1.0x109/L) 
 
Withhold the dose and immediately hospitalize participant with appropriate 
management, per local institutional guidance. 
 
Consider additional supportive treatment per local practice (e.g., growth factors). 
 
Upon recovery, consider at the same dose level of GSK2857916, if neutropenia was 
drug-related. 
Infusion-Related Reactionb 
 
Grade 2 
 
Stop the infusion, provide medical treatment and continue at a reduced rate after 
resolution to Grade 0-1. 
Grade 3 
 
Further treatment with GSK2857916 needs to be discussed with Medical Monitor.  
Continuation only allowed after recovery to ≤Grade 1 and with pre-medication, and 
extension of infusion time to 2-4 hours.  Any future infusion needs to be premedicated. 
Grade 4 
 
Permanently discontinue. 
Pneumonitis 
Grade 2 
 
Withhold treatment with GSK2857916. 
 
Upon recovery to Grade 1, restart treatment at the same dose level. 
 
Rechallenge with the same dose must be discussed with the Medical Monitor. 
Grade 3-4 
 
Permanently discontinue treatment with GSK2857916. 
j. 
Medical Monitor may consult GSK’s nephrology safety panel about plans to continue therapy. 
k. 
If symptoms resolve within 1 hour of stopping infusion, the infusion may be restarted at 1 dose level reduction of the original infusion rate (e.g., from 100 mL/h to 50 mL/h).  
Otherwise, dosing will be held until symptoms resolve and the participant must be pre-medicated for the next scheduled dose. 
 


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6.7.3.2. 
Pomalidomide  
Pomalidomide dose reductions will be permitted in each 28-day treatment cycle (Q4W).  
Permitted dose level -1, level -2, and level -3 reductions for pomalidomide is shown in 
Table 27.  Detailed dose modifications guidelines for pomalidomide-related AEs are 
described in Table 28. 
Table 27 
Permitted Dose Reductions for Pomalidomide 
Starting dose level 
Dose level -1 
Dose level -2 
Dose level -3 
4 mg 
3 mg 
2 mg 
1 mg 
 
Table 28 
Dose Modifications Guidelines for Hematologic and Other Toxicities 
associated with Pomalidomide 
Toxicity 
Dose Modification 
Neutropenia 
Absolute neutrophil count (ANC) <500/μL (<0.5 x 109/L) 
or febrile neutropenia (single temperature of >38.3°C, 
or sustained ≥38°C for >1 hr and ANC <1,000/μL 
[<1 x 109/L]) 
Interrupt pomalidomide treatment, follow complete 
blood counts weekly 
ANC return to ≥1000/μL  
Resume pomalidomide treatment at 1 mg less than the 
previous dose 
Thrombocytopenia 
Platelet count <25,000/μL (<25 x 109/L) 
Platelet count returns to ≥50,000/μL (≥50 x 109/L) 
Interrupt pomalidomide treatment, follow complete 
blood counts weekly 
Resume pomalidomide treatment at 1 mg less than the 
previous dose 
Cutaneous Reactions 
Grade 3 
Hold pomalidomide treatment and restart at the 
physician's discretion at next lower dose level when 
toxicity has resolved to ≤Grade 1 
Grade 4 or blistering 
Permanently discontinue pomalidomide 
Hypersensitivity 
Angioedema and anaphylaxis reactions 
Permanently discontinue pomalidomide 


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Toxicity 
Dose Modification 
For other non-hematologic toxicities judged to be related to pomalidomide 
Grade 3-4 
Hold pomalidomide treatment and restart at the 
physician's discretion at next lower dose level when 
toxicity has resolved to ≤Grade 2 
 
To initiate a new cycle of pomalidomide, the neutrophil count must be ≥500/L, the 
platelet count must be ≥50,000/L (≥50 x 109/L). 
 
In case of neutropenia, the physician should consider the use of growth factors. 
 
If adverse reactions occur after dose reductions to 1 mg, then pomalidomide should 
be discontinued. 
 
Concomitant use of strong CYP1A2 inhibitors (e.g., ciprofloxacin, enoxacin, and 
fluvoxamine) should be avoided.  If strong inhibitors of CYP1A2 must be used, 
reduce pomalidomide dose by 2 dose levels. 
 
6.7.3.3. 
Dexamethasone  
Dexamethasone dose reductions will be permitted in each 28-day treatment cycle (Q4W).  
Permitted dose level -1 and level -2 reductions for dexamethasone are shown in Table 29.  
Detailed dose modification guidelines for dexamethasone-related AEs are described in 
Table 24.  If recovery from toxicities is prolonged beyond 21 days in 28-day cycles, then 
the dose of dexamethasone will be decreased by 1 dose level. 
Table 29 
Permitted Dose Reductions for Dexamethasone 
Starting dose level 
Dose level -1 
Dose level -2 
40 mg (≤75 years of age) 
20 mg 
12 mg 
20 mg (>75 years of age) 
12 mg 
8 mg 
 
6.7.3.4. 
Guidance on Dose Delays  
Table 30 summarizes the guidance on dose delays for Part 2 Arm B.  


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Table 30 
Dose Delays for Part 2 Arm B 
Scenario 
Actions for GSK2857916 
Actions for Pomalidomide and 
Dexamethasone (Pom/Dex) 
1. Delay of only GSK2857916 
After Cycle 1, a window of ±3 days 
is acceptable for GSK2857916 
dosing.  Outside this window, 
treatment should be given on Day 
(D) 1 of the next planned cycle, 
every 4 weeks (Q4W). 
Continue Pom/Dex according to the 
regimen outlined in the schedule of 
activities (SoA). 
2. Delay of only pomalidomide 
Continue GSK2857916 according to 
the schedule, Q4W as outlined in 
the SoA. 
If pomalidomide treatment cannot 
be administered as planned, when a 
participant is ready to resume 
treatment, pomalidomide may be 
restarted at the appropriate time in 
the planned dosing regimen.  If the 
participant is unable to receive 
pomalidomide on D1-D21 of a given 
cycle, treatment could resume on 
D1 of next cycle, and missed 
pomalidomide doses will not be 
made up.  Dexamethasone should 
be administered on the planned 
treatment day. 
3. Delay of only dexamethasone 
Continue GSK2857916 according to 
the schedule, Q4W as outlined in 
the SoA. 
If participant is ready to resume 
treatment, dexamethasone may be 
restarted at the appropriate time in 
the planned dosing regimen (e.g., 
on D1, D8, D15, and D22 Q4W).  If 
the participant is unable to receive 
dexamethasone on D22 of a given 
cycle, treatment could resume on 
D1 of next cycle, and missed 
dexamethasone doses will not be 
made up.  Pomalidomide should be 
administered on the planned 
treatment day. 
4. Delay of Pom/Dex components 
Continue GSK2857916 according to 
the schedule, Q4W as outlined in 
the SoA if Pom/Dex are delayed. 
Follow Pom/Dex delay guidelines as 
outlined above for pomalidomide 
only delay (Scenario 2) or 
dexamethasone only delay 
(Scenario 3). 
5. Delay of both GSK2857916 and 
Pom/Dex 
Follow GSK2857916 only delay 
guidelines as outlined above 
(Scenario 1). 
Follow Pom/Dex delay guidelines as 
outlined above for pomalidomide 
only delay (Scenario 2) or 
dexamethasone only delay 
(Scenario 3). 
6, Permanent discontinuation of 
GSK2857916 
Not applicable 
Pom/Dex will be allowed to continue 
according to the schedule, Q4W as 
outlined in the SoA. 


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Scenario 
Actions for GSK2857916 
Actions for Pomalidomide and 
Dexamethasone (Pom/Dex) 
7. Permanent discontinuation of 
either pomalidomide or 
dexamethasone or both 
Continue GSK2857916 according to 
the schedule, Q4W as outlined in 
the SoA. 
If either pomalidomide or 
dexamethasone is permanently 
discontinued, the remaining drug in 
Pom/Dex combination will be 
allowed to continue. 
6.7.4. 
Management of Hepatitis B+ participants  
 
Management by local hepatology or infectious disease services is required.  If no 
subspecialist support is available, consultation with Medical Monitor is required 
prior to enrolment into the study for participants with positive titres to Hepatitis B. 
 
Participants should be monitored according to SoA Table 4.  
 
Participants who experience clinically significant elevations in liver chemistry 
should follow liver event monitoring and stopping criteria (Section 7.1.2 
andAppendix 5), and careful evaluation should be immediately initiated for 
evaluation of etiology including HBV DNA testing.  
 
Participants who develop detectable HBV DNA levels during study treatment 
should be reviewed by local specialist(s) immediately (within 1 week) and 
appropriate therapy and monitoring instituted. 
 
Study treatment should be withheld, and Medical Monitor should be contacted 
for any participant who develops detectable HBV DNA levels. 
 
Table 31 
Dose Modification Guideline for Hepatitis B Reactivation 
Toxicity 
Grade/description of 
toxicity 
Recommendations 
Hepatitis B 
reactivation 
Detectable HBV DNA 
 Immediate consult with local specialist to 
institute/modify treatment 
 Hold study treatment 
 Contact Medical Monitor promptly - 
agreement with MM must be obtained prior 
to further dosing of study treatment 
 Follow liver monitoring/stopping guidelines 
per protocol for elevation in liver function 
tests. 
 


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6.7.5. 
Corneal Supportive Care Guideline  
Corneal events, which commonly manifests as a superficial microcystic keratopathy, has 
been observed with antibody drug conjugates, including those conjugated to MMAF.  
Further information regarding corneal event associated with GSK2857916, including a 
grading scale and prophylactic measures are in Appendix 7. 
Sites are required to establish a close collaboration with an ophthalmologist who will be 
responsible for assessing participants and managing those who develop corneal events in 
close communication with Medical Monitor and possibly a GSK ophthalmologist.  
Participants will be assessed by an ophthalmologist at baseline and every 3 weeks for 
Part 1 and Part 2 Arm A or every 4 weeks for Part 2 Arm B. If there are no corneal signs 
per the GSK scale at time specified in SoA, participants may have their ophthalmologic 
exams decreased to once every 3 months. If a participant subsequently develops ocular 
symptoms, the participant should be evaluated by an ophthalmologist. Intraocular 
pressure must be monitored if steroid eye drops are used continuously for more than 7 
days. 
Participants who have corneal signs per the GSK scale at EOT will continue to be 
followed at 3 weeks after the EOT visit and then every 6 weeks for up to 12 months, or 
until full resolution of findings defined as a return to participant’s baseline, or deemed 
clinically stable by an ophthalmologist, whichever comes first. 
In case a dose reduction is necessary, the study treatment will be administered as follows 
as shown in Section 6.7. 
6.8. 
Continued Access to Study Intervention after the End of the 
Study  
Study participants that continue to benefit from study intervention beyond the final 
analysis DCO date will continue to have access to study intervention until the EOS as 
defined in Section 4.4. There is no planned intervention following the EOS. 
The investigator is responsible for ensuring that consideration has been given to the post-
study care of the participant’s medical condition. 
Refer to Section 8.3.1 for follow-up assessments from the final DCO date to the EOS. 
6.8.1. 
Continued Access to Study Intervention After Data Cut-off prior 
to EOS  
Participants receiving study treatment at the time of the final analysis DCO date may 
continue to receive study treatment, if in the opinion of their treating physician, they are 
benefiting from continued treatment, and they do not meet any protocol-defined treatment 
discontinuation criteria (see Section 7.1). Study treatment will continue until a study 
treatment discontinuation criterion (see Protocol Section 7.1), as assessed by the 
investigator, has been met.  


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Participants who continue study treatment in the PACT phase will be cared for in 
accordance with local standard clinical practice, at a participant's particular site. 
Participants will continue to be monitored for all SAEs, AEs leading to treatment 
discontinuation, prespecified ocular data, overdoses and pregnancy cases while receiving 
study drugs.  Information relating to participant care will be recorded on participant 
medical records, with the exception of SAEs, AEs leading to treatment discontinuation, 
prespecified ocular data, overdoses and pregnancy cases that must continue to be reported 
to GSK, will not otherwise be reported for the purposes of this study.  Investigators must 
report all SAEs, AEs leading to treatment discontinuation, overdose and pregnancy cases 
until 70 days after the participant’s last dose of study treatment in accordance with 
Section 8.3.1. Prespecified ocular data will be reported until resolution unless the event is 
considered by the investigator to be unlikely to resolve, or the patient is lost to follow up. 
During the PACT phase, reporting and follow up of SAEs, overdose and pregnancy cases 
and prespecified ocular data will be done via paper forms. All other assessments will 
revert to standard of care at their site. 
7. 
DISCONTINUATION OF STUDY TREATMENT AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL  
7.1. 
Discontinuation of Study Treatment  
Participants will receive study treatment until disease progression, unacceptable toxicity, 
or withdrawal of consent (including but not restricted to meeting stopping criteria for 
significant toxicity as outlined below). 
Study treatment may be permanently discontinued for any of the following reasons: 
 
disease progression or unacceptable toxicity 
 
participant has met any of the protocol defined safety stopping criteria 
 
deviation(s) from the protocol 
 
request of the participant or proxy (withdrawal of consent by participant or 
proxy) 
 
investigator’s discretion 
 
concurrent illness that prevents further administration of study treatment. 
 
participant is lost to follow-up (see Section 7.3) 
 
pregnancy 
 
study is closed or terminated. 
Once a participant has permanently discontinued from study treatment, the participant 
will not be allowed to re-enter the study. The primary reason study treatment was 
permanently discontinued must be documented in the participant’s medical records and 
eCRF. If the participant voluntarily discontinues from treatment due to toxicity, AE must 
be recorded as the primary reason for permanently discontinuation on the eCRF. 


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If study treatment is permanently discontinued, the participant will remain in the study to 
be evaluated for safety. See the SoA for data to be collected at the time of discontinuation 
of study treatment. 
7.1.1. 
Discontinuation of Individual Components of Combination Study 
Treatment in Part 2  
At the discretion of the investigator, participants who discontinue bortezomib and 
dexamethasone (Arm A) or pomalidomide and dexamethasone (Arm B) may continue 
GSK2857916 monotherapy until disease progression, unacceptable toxicity, or 
withdrawal of consent.  Similarly, participants in Arm A who discontinue GSK2857916 
may continue bortezomib and dexamethasone until completion of 8 cycles (after which 
they should attend an EOT Visit and be followed up according to the SoA), disease 
progression, unacceptable toxicity, or withdrawal of consent.  Participants in Arm B who 
discontinue GSK2857916 may continue pomalidomide and dexamethasone until disease 
progression, unacceptable toxicity, or withdrawal of consent. 
The primary reason for discontinuation of each study treatment must be documented 
independently in the medical record and on the eCRF. 
7.1.2. 
Liver Chemistry Stopping Criteria  
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology. The diagram below illustrates 
Liver Stopping Event Algorithm (Figure 5). 
Figure 5 
Liver Chemistry Stopping Criteria – Liver Stopping Event Algorithm  
 


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Refer to Appendix 5 for required Liver Safety Actions and Follow up Assessments and 
for required process for study treatment restart/rechallenge if considered for the 
participant. 
7.1.2.1. 
Study Treatment Restart or Rechallenge after Liver Stopping Criteria 
Met  
A participant who met liver chemistry stopping criteria cannot resume study treatment 
unless all of the following conditions are met: 
 
GSK approval is granted (as described below) 
 
Institutional Review Board/Independent Ethics Committee (IRB/IEC) approval is 
obtained 
 
Separate informed consent form (ICF) for study treatment restart/rechallenge is 
signed by the participant and participant is informed of any associated risks 
If GSK approval to restart/rechallenge the participant with study treatment is not 
granted, then the participant must permanently discontinue study treatment and may 
continue in the study for protocol-specified follow up assessments. 
7.1.3. 
QTc Interval Stopping Criteria  
If a participant that meets the corrected QT (QTc) interval duration criteria below, study 
treatment(s) will be withheld. 
 
QT interval corrected for heart rate by Fridericia’s formula (QTcF = QT / 
RR0.33) >530 msec 
OR 
 
Increase of QTcF by ≥60 msec from baseline 
If an ECG demonstrates a prolonged QT interval, obtain 2 additional ECGs over a 
brief period (e.g., within approximately 10 minutes of the abnormal ECG, if possible, 
and approximately 10 minutes apart from each other), and then use the averaged QTc 
values of the 3 ECGs to determine whether the participants should have study 
treatment(s) withheld.  The QTc should be based on single or averaged QTc values 
of triplicate electrocardiograms obtained over a brief (e.g., 5-10 minutes) recording 
period.   
The QT interval should be corrected for heart rate by Fridericia’s formula (QTcF). 
7.1.4. 
Left Ventricular Ejection Fraction (LVEF) Stopping Criteria  
Echocardiography must be performed at Screening and the EOT visit.  If an ECHO is 
done at any point during the study, the following stopping criteria are to be employed.  
Participants who have an asymptomatic absolute decrease of >10% in LVEF and the 
ejection fraction is below the institution’s lower limit of normal (LLN) should 
temporarily discontinue study treatment and have a repeat evaluation of LVEF within 
1 week.  Echocardiogram (ECHO) should be repeated every 1 to 2 weeks for 4 weeks or 
until LVEF recovery to above institutional LLN and within 10% of baseline.  


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 
If the LVEF recovers (defined as  institutional LLN and absolute decrease 10% 
compared with baseline) at any time during the next 4 weeks, after consultation with 
and approval from the Medical Monitor, the participant may be restarted on 
GSK2857916 at a reduced dose.  For such participants, monitoring of LVEF will be 
performed 2 and 4 weeks after rechallenge, then every 4 weeks for a total of 
16 weeks 
 
If repeat LVEF does not recover within 4 weeks, treatment must be permanently 
discontinued.  Ejection fraction must be monitored every 4 weeks for a total of 
16 weeks or until resolution (whichever occurs first). 
Participants with Grade 3 or 4 (symptomatic) left ventricular systolic dysfunction must 
interrupt treatment with GSK2857916.  Ejection fraction must be monitored every 
4 weeks for a total of 16 weeks or until resolution.  If recovery occurs 
(LVEF  institutional LLN and symptom resolution) within 4 weeks, then treatment with 
GSK2857916 may be restarted at a reduced dose in consultation with the medical 
monitor. 
7.1.5. 
Corneal Event Stopping Criteria  
Corneal events should be graded according to the guidelines provided in Appendix 7.  
The investigator must discuss the participants who develop a Grade 4 corneal event with 
the Medical Monitor to determine whether the participant can be allowed to continue 
treatment with GSK2857916 or whether GSK2857916 should be permanently 
discontinued.  If a participant is allowed to continue on study, the dose of GSK2857916 
will be reduced by at least 25%, and the treatment will only be allowed to continue upon 
recovery to Grade 1 or less.  The decision will be documented in study files, together 
with individual assessment of risk-benefit. For details on re-start guidance, see Table 17 
for Part 1 and Table 20 for Part 2. 
7.1.6. 
Infusion-Related Reaction Management and Stopping Criteria  
Premedication is not required prior to infusion unless deemed medically appropriate by 
the investigator following evaluation of IRRs.  Premedication should be considered in 
any participant who experienced an IRR at first or any subsequent infusion with 
GSK2857916. 
IRRs should be managed by guidelines provided in Section 6.7. A participant that 
experiences a Grade 4 IRR should be permanently withdrawn from the study. 
7.1.7. 
Allergic and Anaphylactic Reaction Stopping Criteria  
All participants will be monitored carefully for evidence of allergic response.  A 
participant that exhibits signs or symptoms of severe hypersensitivity or anaphylaxis will 
receive appropriate medical treatment and be permanently withdrawn from the study. 
In accordance with the preparedness for treatment of anaphylaxis, emergency 
resuscitation equipment, advanced cardiac life support equipment, and medications must 
be readily accessible during GSK2857916 administration. 


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It is important to recognize early signs of an anaphylaxis reaction and appropriate 
treatment must begin immediately to prevent progression to severe anaphylaxis. 
Participants will be closely monitored in an appropriate setting for early signs of dyspnea 
and edema. Antihistamines, such as diphenhydramine; and corticosteroids such as 
prednisone may be given to reduce symptoms. 
If more severe clinical signs arise, immediate assessment of the ABC’s (airway, 
breathing, and circulation from Basic Life Support) will be done in all suspected 
anaphylactic reactions. Cardio-Pulmonary Resuscitation (CPR) will be initiated if 
needed. Epinephrine will be given by injection without delay. Emergency interventions 
may include endotracheal intubation or tracheostomy. Treatment for shock will include 
IV fluids and medications that support the actions of the heart and circulatory system. 
7.2. 
Participant Discontinuation/Withdrawal from the Study  
 
A participant may withdraw from the study at any time at his/her own request, 
or may be withdrawn at any time at the discretion of the investigator for safety, 
behavioral, compliance or administrative reasons. 
 
If the participant withdraws consent for disclosure of future information, the 
sponsor may retain and continue to use any data collected before such a 
withdrawal of consent. 
 
If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the investigator must document this in the site 
study records. 
 
Refer to the SoA for data to be collected at the time of study discontinuation 
follow-up and for any further evaluations that need to be completed. 
7.3. 
Lost to Follow Up  
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site.  
The following actions must be taken if a participant fails to return to the study site for a 
required study visit: 
 
The site must attempt to contact the participant and reschedule the missed visit 
as soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study 
 
Before a participant is deemed lost to follow up, the investigator or designee 
must make every effort to regain contact with the participant (where possible, 
3 telephone calls and, if necessary, a certified letter to the participant’s last 
known mailing address or local equivalent methods). These contact attempts 
should be documented in the participant’s medical record 
 
Should the participant continue to be unreachable, he/she will be considered to 
have withdrawn from the study. 


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 
Discontinuation of specific sites or of the study as a whole are handled as part of 
Appendix 1. 
8. 
STUDY ASSESSMENTS AND PROCEDURES  
A signed, written informed consent form must be obtained from the participant prior to 
any study-specific procedures or assessments being performed. The timing of each 
assessment is listed in the SoA (Section 1.3). 
A list of clinical laboratory tests is displayed in Table 32. 
Whenever vital signs, 12-lead electrocardiograms (ECGs) and blood draws are scheduled 
for the same nominal time, blood draws must occur last.  The timing of the assessments 
must allow the blood draw to occur at the exact nominal time.  Detailed procedures for 
obtaining each assessment are provided in the SRM. 
 
Study procedures and their timing are summarized in the SoA (Section 1.3) 
 
Protocol waivers or exemptions are not allowed 
 
Demographic and baseline assessments will include year of birth, sex, race, and 
ethnicity. 
 
Medical/medication/family history will be assessed as related to the 
inclusion/exclusion criteria listed in Section 5.1 and Section 5.2 
 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or 
discontinue study treatment 
 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct 
 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening 
log to record details of all participants screened and to confirm eligibility or record 
reasons for screening failure, as applicable 
 
Procedures conducted as part of the participant’s routine clinical management (e.g., 
blood count) and obtained before signing of ICF may be utilized for screening or 
baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in the SoA 
 
Visit Window:  
 
Baseline disease assessments must be completed with 21 days prior to dosing 
start unless otherwise specified.  Refer to SoA (Section 1.3) 
 
Screening assessments performed within the permitted time do not need to be 
repeated on C1D1 unless otherwise specified 
 
Safety labs completed within 72 hours of first dose do not need to be repeated 
on C1D1 


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 
Part 1 and Part 2 Arm A: Pregnancy testing may be completed within 72 hours 
prior to first dose 
Part 2 Arm B: Two negative serum pregnancy tests must be obtained prior to 
initiating treatment; the first test should be performed within 10 to 14 days of 
C1D1, but the second must be performed within 24 hours of C1D1. 
 
ECHO must be completed within 35 days prior to first dose 
 
Imaging may be completed within 30 days prior to first dose 
 
Bone marrow (BM) archival tissue from up to 60 days prior to study is 
acceptable 
 
Part 1: For C1D2 assessments, no time window is permitted.  C1D8 and C1D15 
assessments can be performed within ±1 day of scheduled occurrence. 
Part 2 Arm A: D4, D8, and D11 assessments of each cycle can be performed 
within ±1 day of scheduled occurrence.  Other assessments at non-dosing days 
can be performed within ±3 days of scheduled occurrence unless otherwise 
specified. 
Part 2 Arm B: D8, D15, and D22 assessments of each cycle can be performed 
within ±1 day of scheduled occurrence.  Other assessments at non-dosing days 
can be performed within ±3 days of scheduled occurrence unless otherwise 
specified. 


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Table 32 
List of clinical Laboratory Tests 
Hematology1 
Platelet count  
RBC Indices: 
Automated WBC 
Differential: 
Red blood cell (RBC) count 
Mean corpuscular volume (MCV) 
Neutrophils 
White blood cell (WBC) 
count (absolute)  
Mean corpuscular hemoglobin (MCH) 
Lymphocytes 
Reticulocyte count 
Mean corpuscular hemoglobin concentration (MCHC) 
Monocytes 
Hemoglobin 
 
Eosinophils 
Hematocrit 
 
Basophils 
Clinical Chemistry1 
Blood urea nitrogen (BUN) 
Potassium 
Aspartate aminotransferase 
(AST) 
Total and direct bilirubin 
Creatinine   
Chloride 
Alanine aminotransferase 
(ALT) 
Uric Acid 
Glucose 
Spot urine (albumin / 
creatinine ratio) 
Gamma glutamyl 
transferase (GGT) 
Albumin 
Sodium 
Calcium 
Alkaline phosphatase (ALP) 
Total Protein 
Magnesium 
Phosphorous 
Creatine kinase (CK) 
Lactate dehydrogenase 
(LDH) 
Estimated glomerular 
filtration rate (eGFR) 
 
 
 
Urine1 
Routine Urine Dipstick (Urinalysis required if blood or protein is detected by dipstick) 
Specific gravity 
pH, glucose, protein, blood and ketones by dipstick 
Microscopic examination (if blood or protein is abnormal) 
Other Safety 
C-reactive protein (CRP)1 
Troponin I or T4 
B-type natriuretic peptide (BNP)4 
Follicle stimulating hormone (FSH) and estradiol (as needed in women of non-childbearing potential only) 
(screening)1 
Pregnancy test (urine or blood per local practice)1 
Hepatitis B surface antigen (HBsAg)1 
Hepatitis B surface antibody (HbsAb)1 
Hepatitis B core antibody (HbcAb)1 
Hepatitis B virus DNA (HBV DNA) 1 
Hepatitis C (Hep C antibody)1: 
Note: Hepatitis C RNA testing is optional but may be done to determine participant eligibility if hepatitis C antibody 
positive.  Participants with positive hepatitis C antibody due to prior resolved disease may be offered hepatitis C 
RNA testing to determine eligibility. 
PK/ADA  
Pharmacokinetics (PK)2 
Anti-drug antibodies (ADA)2, 3 
Optional Testing 
Genetics2 
 


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Disease Evaluation Laboratory Tests 
Urine protein 
Electrophoresis 
(UPEP)1 
Urine Immunofixation1 
24-hour urine 
collection for M-
protein1 
Calcium corrected for 
albumin (serum)
1 
Serum Protein 
Electrophoresis 
(SPEP)1 
Serum M-protein calculation1 Serum 
Immunofixation1 
Beta2 microglobulin1 
Serum kappa, lambda 
FLC, FLC ratio1 
IgG, IgA, IgM. 
IgD and IgE only in 
participants with IgD or IgE 
myeloma 
  
 
Bone Marrow Aspiration/Biopsy 
Bone marrow for disease assessment1 
Bone marrow biopsy to confirm sCR by IHC1 
Bone marrow for FISH testing5 
1. To be performed at local laboratory.   
3. Not needed at screening 
4. If not available from local laboratory, it can be performed at central laboratory. 
5. FISH testing at least for: t(4;14), t(14;16), 17p13del.  BM samples from within 60 days prior to first dose are 
acceptable for FISH analysis. 
8.1. 
Efficacy Assessments  
Standard disease assessments for RRMM will include the following assessments:  
 
UPEP, Urine Immunofixation, 24 hr collection for urine M-protein 
 
SPEP, Serum M-protein, Serum Immunofixation 
 
Calcium corrected for albumin 
 
IgG, IgM, IgA 
 
IgD, IgE (only in participants with IgD or IgE myeloma)  
 
Serum Kappa, lambda FLC, FLC ratio 
 
Bone marrow aspirate at screening and to confirm CR and biopsy for 
immunohistochemistry (IHC) to confirm sCR. 
 
Imaging of extramedullary disease (in participants with extramedullary disease) 
 
CT, MRI, or PET/CT is required upon achieving CR or sCR 
 
Skeletal surveys at screening and as clinically indicated. 
Response evaluation will be performed according to the IMWG Uniform Response 
Criteria for Multiple Myeloma [Kumar, 2016]. 
CCI
CCI


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Baseline serum/urine disease assessment will be completed during screening period 
(within 21 days prior to the first dose of study treatment) and baseline imaging within 
30 days prior to the first dose of study treatment.  On study serum and urine-based 
assessments (M-protein, FLC, immunofixation) will be performed as specified in the SoA 
(Section 1.3).  Details for the preparation and shipment of samples for central laboratory 
assessments will be provided in the SRM. 
In participants with extramedullary plasmacytoma, the disease assessments must include 
imaging (e.g., CT, MRI, or PET/CT scans- the same method should be used throughout 
the study) and physical examination (as indicated for palpable/superficial lesions).  
For participants who are followed by imaging for extramedullary disease the imaging has 
to be performed as described in the SoA (Section 1.3). 
All assessments on study must be performed on a calendar schedule and must not be 
affected by dose interruptions/delays.  For post-baseline assessments, a window of 
3 days is permitted to allow for flexible scheduling. 
The confirmation of progressive disease must be performed within 14 days, but NOT on 
the same day, and NOT from the same blood draw as the initial test documenting 
progressive disease.  The assessments of anti-myeloma activity will be performed during 
the EOT Visit as described in the SoA (Section 1.3).  
If the last imaging assessment was greater than or equal to 8 weeks prior to the 
participant’s discontinuation from study treatment and progressive disease has not been 
documented, a new disease assessment must be obtained at the time of discontinuation 
from study treatment. 
8.2. 
Safety Assessments  
Planned time points for all safety assessments are provided in the SoA. 
8.2.1. 
Physical Examinations  
At screening, on dosing days, and at EOT visit a full physical examination will include 
assessments of the head, eyes, ears, nose, throat, skin, thyroid, lungs, cardiovascular, 
abdomen (liver and spleen), lymph nodes, and extremities.  Height and weight will also 
be measured at Screening and recorded, with weight repeated at the start of each cycle. 
During the physical examinations, investigators should pay special attention to clinical 
signs related to previous serious illnesses and record any changes noted during study 
treatment, if any. 
8.2.2. 
Ocular Examinations and Procedures  
A full baseline ophthalmic examination for all participants must include, but is not 
limited to: 
1. Best corrected visual acuity  


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2. Documentation of manifest refraction used to obtain best corrected visual acuity 
3. Current glasses prescription (if applicable) 
4. Pupillary light reflex 
5. Extraocular muscle movements (graded from 1 to 4 with (+) sign indicating over 
action, (-) sign indicating under action and 0 representing normal movements 
6. Intraocular pressure measurement and time checked 
7. Full anterior segment examination including fluorescein staining of the cornea: 
 
Anterior segment exam (slit lamp) includes: orbit/lids/adnexa, conjunctiva, 
sclera, cornea, anterior chamber, iris, lens and anterior vitreous. 
8. Anterior segment photography of a fluorescein stained cornea 
9. Dilated funduscopic exam: fundus photography with interpretation 
The on-treatment and follow-up ophthalmic exam must include everything except, dilated 
funduscopic exam, including fundus photography, anterior segment photography, 
extraocular muscle movements, (which must be performed as clinically indicated) and 
current glasses prescription (if applicable). 
The last follow-up visit should also include anterior segment photography of a fluorescein 
stained cornea. 
The EOT ophthalmic exam should match the baseline (screening) exam. 
Additional examinations should be performed at the discretion of the treating eye 
specialist. 
8.2.3. 
ECOG Performance Status  
Participant performance status will be assessed as specified in the SoA (Section 1.3), 
using the Eastern Cooperative Oncology Group (ECOG) scale, provided in Appendix 6. 
8.2.4. 
Vital Signs  
Vital sign measurements must include systolic and diastolic blood pressure, temperature, 
and pulse rate.  Vital signs must be measured after resting for at least 5 minutes.  Vital 
signs must be measured more frequently if warranted by the clinical condition of the 
participant.  On days where vital signs are measured multiple times, temperature does not 
need to be repeated unless clinically indicated. 
8.2.4.1. 
First Infusion  
Monitoring intervals: Vital signs must be monitored at designated time points related to 
drug infusion as specified in the SoA (Section 1.3).  In general, participants must also be 
monitored for at least 1 hour after the completion of the first infusion and may be 
discharged if considered clinically stable and all other study procedures have been 
completed. 


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8.2.4.2. 
Subsequent Infusions  
Monitoring intervals: Vital signs must be monitored at designated time points related to 
drug infusion as specified in the SoA (Section 1.3).  Participants may be discharged after 
the infusion has been completed if considered clinically stable and all other study 
procedures have been completed. 
8.2.5. 
Electrocardiograms  
Singlet 12-lead ECGs must be obtained at designated time points specified in the SoA 
(Section 1.3).  The ECG machine must automatically calculate the heart rate and measure 
PR, QRS, QT, and corrected QT (QTc) intervals.  At each assessment, a 12-lead ECG 
must be performed by qualified personnel at the site after the participant has at least a 
5-minute rest. 
8.2.6. 
Echocardiogram  
Echocardiograms (ECHOs) must be performed at baseline to assess cardiac ejection 
fraction for the purpose of study eligibility, as specified in the SoA (Section 1.3).  The 
evaluation of the echocardiographer must include an evaluation for LVEF.  If an ECHO 
is performed on study the results must be documented in the eCRF. 
8.2.7. 
Clinical Safety Laboratory Assessments  
 
Refer to Table 32 for the list of clinical laboratory tests to be performed and to 
the SoA for the timing and frequency 
 
The investigator must review the laboratory report, document this review, and 
record any clinically relevant changes occurring during the study in the AE 
section of the CRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which 
are not associated with the underlying disease, unless judged by the investigator 
to be more severe than expected for the participant’s condition 
 
All laboratory tests with values considered clinically significantly abnormal 
during participation in the study or within 70 days after the last dose of study 
treatment should be repeated until the values return to normal or baseline or are 
no longer considered significantly abnormal by the investigator or medical 
monitor 
 
If such values do not return to normal/baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor 
notified 
 
All protocol-required laboratory assessments, as defined in Table 32, must be 
conducted in accordance with the laboratory manual and the SoA. 
8.3. 
Adverse Events and Serious Adverse Events  
The definitions of an AE or SAE can be found in Appendix 2. 


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Adverse events will be coded using the standard Medical Dictionary for Regulatory 
Activities (MedDRA) and grouped by system organ class.  Adverse events, aside from 
corneal events, will be graded by the investigator according to the NCI-CTCAE, 
(version 4.03).  Corneal events associated with GSK2857916 will be graded according to 
the grading scale provide in Appendix 7. 
The investigator and any qualified designees are responsible for detecting, documenting, 
and reporting events that meet the definition of an AE or SAE and remain responsible for 
following up Aes that are serious, considered related to the study treatment or the study, 
or that caused the participant to discontinue the study treatment or the study (see 
Section 7.1 and Section 7.1.1). 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information  
 
All SAEs will be collected from the start of treatment until 70 days following 
discontinuation of study treatment regardless of initiation of a new cancer 
therapy or transfer to hospice at the time points specified in the SoA 
(Section 1.3).  However, any SAEs assessed as related to study participation 
(e.g., study treatment, protocol-mandated procedures, invasive tests, or change 
in existing therapy) or related to a GSK product will be recorded from the time a 
participant consents to participate in the study up to and including any 
follow-up. 
 
All Aes will be collected continually from the start of treatment until 70 days 
following discontinuation of study treatment regardless of initiation of a new 
cancer therapy or transfer to hospice at the time points specified in the SoA 
(Section 1.3) 
 
Medical occurrences that begin before the start of study treatment but after 
obtaining informed consent will be recorded on the Medical History/Current 
Medical Conditions section of the eCRF not the AE section 
 
All SAEs will be recorded and reported to the sponsor or designee immediately 
and under no circumstance should this exceed 24 hours, as indicated in 
Appendix 2. The investigator will submit any updated SAE data to the sponsor 
within 24 hours of it being available 
 
Investigators are not obligated to actively seek Aes or SAEs after the conclusion 
of the study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the 
study, and he/she considers the event to be reasonably related to the study 
treatment or study participation, the investigator must promptly notify the 
sponsor 
 
For participants in the PACT phase of the study, GSK will continue to collect 
safety information including SAEs, Aes leading to treatment discontinuation, 
prespecified ocular data, overdose and pregnancy cases via paper forms which 
will be reported directly to GSK. SAEs, Aes leading to treatment 
discontinuation, overdose and pregnancy cases will be reported during the 
PACT treatment period and for up to 70 days after last dose and pre-specified 


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ocular data will be reported until resolution unless the event is considered by the 
investigator to be unlikely to resolve, or the patient is lost to follow up. 
Additionally, any SAEs that are ongoing at the time of the final DCO must be 
followed up to resolution unless the event is considered by the investigator 
unlikely to resolve, or the patient is lost to follow-up. Updates to these events 
will also occur via paper forms directly to GSK.  
Follow up of ocular data after the start of PACT: 
1) For participants continuing on GSK2857916 as part of PACT: 
Ocular exam schedule during PACT treatment:  
 
For participants before completing the 6th dose of GSK 2857916: ophthalmic 
exams to be performed by an ophthalmologist every cycle prior to dosing, up 
to, and including, the 6th dose of GSK2857916. 
 
For participants completing the 6th dose of GSK 2857916: Participants 
without ocular (including corneal) examinations findings, symptoms or vision 
changes when entering the PACT phase, and up to and including the 6th GSK 
2857916 dose, may have their ocular assessment decreased to at least every 3 
months, or as clinically indicated, until the end of treatment. For participants 
who at the time of entering PACT and/or during PACT doses, have ocular 
(including corneal) examinations findings, symptoms or vision changes, the 
ocular assessment will occur (increase to) every cycle (and prior to the next 
GSK2857916 infusion if dosing), until resolution (GSK Grade 1 or baseline). 
After resolution, the ocular exam assessment frequency reduces to at least 
every 3 months, or as clinically indicated, until the end of treatment. 
Ocular exam schedule after end of PACT treatment: Participants with treatment-
related ocular (including corneal) examination findings, symptoms, or vision changes 
at the end of PACT treatment have ocular assessments at least every 3 months, or 
more frequently as clinically indicated, for up to 12 months from the end of 
treatment or until resolution (to GSK Grade 1 or baseline), or withdrawal of consent, 
whichever comes first. For participants without ocular (including corneal) 
examination findings, symptoms, or vision changes at the end of PACT treatment no 
further ocular exams are required. 
2) For participants who stopped GSK2857916 prior to PACT but have ongoing ocular 
events at the time of final study data-cut-off/start of PACT: 
 
Participants with treatment-related ocular (including corneal) examination 
findings, symptoms, or vision changes at the start of PACT have ocular 
assessments at least every 3 months, or more frequently as clinically indicated, 
for up to 12 months from the end of treatment or until resolution (GSK Grade 1 
or baseline), or withdrawal of consent, whichever comes first. 
GSK retains the right to request additional information for any patient with ongoing 
AE(s)/SAE(s) at EOS, if judged necessary. 


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8.3.2. 
Method of Detecting AEs and SAEs  
 
The method of recording, evaluating, and assessing causality of AEs and SAEs 
and the procedures for completing and transmitting SAE reports are provided in 
Appendix 2. 
 
Care will be taken not to introduce bias when detecting AE and/or SAE. 
Open-ended and non-leading verbal questioning of the participant is the 
preferred method to inquire about AE occurrence. 
8.3.3. 
Follow-up of AEs and SAEs  
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs and non-serious AEs of special 
interest (as defined in Section 8.3.5), will be followed until the event is resolved, 
stabilized, otherwise explained, or the participant is lost to follow-up (as defined in 
Section 7.3). Further information on follow-up procedures is given in Appendix 2. 
8.3.4. 
Regulatory Reporting Requirements for SAEs  
 
Prompt notification by the investigator to the sponsor of a SAE is essential so 
that legal obligations and ethical responsibilities towards the safety of 
participants and the safety of a study treatment under clinical investigation are 
met 
 
The sponsor has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study treatment 
under clinical investigation. The sponsor will comply with country-specific 
regulatory requirements relating to safety reporting to the regulatory authority, 
IRB/IEC, and investigators 
 
Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions (SUSAR) according to local regulatory requirements and 
sponsor policy and forwarded to investigators as necessary 
 
An investigator who receives an investigator safety report describing a SAE or 
other specific safety information e.g., summary or listing of SAE) from the 
sponsor will review and then file it along with the IB and will notify the 
IRB/IEC, if appropriate according to local requirements 
8.3.5. 
Adverse Events of Special Interest  
AESI for GSK2857916 are corneal events, thrombocytopenia and IRRs.  The severity of 
corneal events associated with GSK2857916 and related ophthalmic exam findings or 
visual acuity will be graded using the scale provided in Table 37.  The severity of corneal 
events and other AESI will be graded utilizing NCI-CTCAE.  Guidelines for dose 
modifications and interruptions for management of common toxicities associated with the 
study treatment are provided in Section 6.7. 


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8.3.6. 
Pregnancy  
Do not collect pregnancy information for female participants known to be pregnant 
during the screening phase or before exposure to study. 
The need for a screening pregnancy test depends on whether a female participant is of 
childbearing potential or non-childbearing potential. 
If a female participant in Part 1 or Part 2 Arm A is of childbearing potential, she must 
have a serum pregnancy test performed within 72 hours prior to the first dose of 
GSK2857916, and the result must be negative.  For questionable cases, 
follicle-stimulating hormone (FSH) and estradiol (as needed) should be performed at 
local lab to determine childbearing potential.  Subsequent pregnancy tests on dosing days 
may be either serum or urine.  Final pregnancy test (serum or urine) must be performed at 
the EOT Visit.  Follow up pregnancy assessment by telephone (for female participants 
with childbearing potential only) should be performed 4 months after the last dose of 
GSK2857916 or 7 months after the last dose of bortezomib (only Part 2 Arm A), 
whichever is longest. 
If a female participant in Part 2 Arm B is of childbearing potential, she must have a 
serum pregnancy test at screening.  Two negative serum pregnancy tests must be obtained 
prior to initiating treatment; the first test should be performed within 10 to 14 days of the 
first dose of GSK2857916, but the second must be performed within 24 hours of the first 
dose of GSK2857916.  After the first dose, pregnancy test will be done weekly during the 
first month, then every cycle thereafter (or every 2 weeks in females with irregular 
menstrual cycles).  Subsequent pregnancy test on dosing days may be either serum or 
urine test.  Each pregnancy test must be performed within 24 hours prior to dosing.  Final 
pregnancy test (serum or urine) must be performed in female participants of childbearing 
potential at the EOT visit and at 2 weeks (in case of irregular menses) and 4 weeks 
following treatment discontinuation.  Follow up pregnancy assessment by telephone (for 
female participants of childbearing potential only) should be performed 4 months after 
the last dose of GSK2857916 or 4 weeks after the last dose of pomalidomide, whichever 
is longest. 
 
Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study and for 4 months following 
the last dose of GSK2857916, 7 months following the last dose of bortezomib 
(only Part 2 Arm A), and 4 weeks following the last dose of pomalidomide (only 
Part 2 Arm B), whichever is longest 
 
Investigator will attempt to collect pregnancy information on any male 
participant’s female partner who becomes pregnant while participating in this 
study and for 6 months following the last dose of GSK2857916, 4 months 
following the last dose of bortezomib (only Part 2 Arm A), and 4 weeks 
following the last dose of pomalidomide (only Part 2 Arm B), whichever is 
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 
If a pregnancy is reported, the investigator should inform GSK within 24 hours 
of learning of the pregnancy and should follow the procedures outlined in 
Appendix 2 
 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, 
stillbirth, congenital anomalies, ectopic pregnancy) are considered SAE. 
8.3.7. 
Cardiovascular and Death Events  
The Death CRF is provided immediately after the occurrence or outcome of death is 
reported.  Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
For any cardiovascular events detailed in Appendix 2 and all deaths, whether or not they 
are considered SAEs, specific Cardiovascular and Death sections of the eCRF will be 
required to be completed.  These sections include questions regarding cardiovascular 
(including sudden cardiac death) and non-cardiovascular death. 
The Cardiovascular eCRFs are presented as queries in response to reporting of certain 
cardiovascular MedDRA terms.  The cardiovascular information must be recorded in the 
specific cardiovascular section of the eCRF within one week of receipt of a 
Cardiovascular Event data query prompting its completion. 
8.3.8. 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as SAEs  
Disease progression does not need to be reported as a SAE.  Death due to disease under 
study is to be recorded on the Death electronic eCRF.  However, if the underlying disease 
(i.e., progression) is greater than that which would normally be expected for the 
participant, or if the investigator considers that there was a causal relationship between 
treatment with study treatment(s) or protocol design or procedures and the disease 
progression, then this must be reported as a SAE. 
8.4. 
Treatment of Overdose  
There is no specific antidote for an overdose of GSK2857916.  GSK does not recommend 
a specific treatment for an overdose of GSK2857916. 
In the event of an overdose, the investigator should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for AE/SAE and laboratory abnormalities until study 
treatment can no longer be detected systemically (at least 90 days). 
3. Obtain a plasma sample for PK analysis and a blood sample for 
 within 
24 hours of the event study treatment if requested by the Medical Monitor 
(determined on a case-by-case basis). 
4. Document the quantity of the excess dose as well as the duration of the overdosing in 
the CRF. 
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Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant. 
There is no known specific antidote for pomalidomide, bortezomib, or dexamethasone 
overdose. 
No specific information is available on the treatment of overdose with pomalidomide.  
Hemodialysis can remove pomalidomide from circulation [Pomalyst, 2019].   
In the event of an overdose of bortezomib, the participant’s vital signs should be 
monitored, and appropriate supportive care given to maintain blood pressure (such as 
fluids, pressors, and/or inotropic agents) and body temperature [VELCADE, 2019].   
For dexamethasone, it is difficult to define an excessive dose of a corticosteroid as the 
therapeutic dose will vary according to indication and participant requirements.  
Exaggeration of corticosteroid related adverse effects may occur.  Treatment should be 
asymptomatic and supportive as necessary [LenaDex, 2019]. 
For further information, see the SRM for prescribing information. 
8.5. 
Pharmacokinetics  
8.5.1. 
Blood Sample Collection for Pharmacokinetics  
Blood samples for PK analysis of GSK2857916 (intact ADC and total mAb) and 
cys-mcMMAF will be collected at the time points indicated in the SoA (Section 1.3), 
Table 33, Table 34, and Table 35.  Each PK sample must be collected as close as possible 
to the planned time relative to the dose (which is 0 h) administered to the participant on 
PK days.  The actual date and time of each blood sample collection will be recorded. 
Details on PK blood sample collection, processing, storage, and shipping procedures are 
provided in the SRM. 
8.5.2. 
Pharmacokinetic Sample Analysis  
Plasma analysis will be performed under the control of GSK Platform Technology and 
Sciences (PTS)-Bioanalysis Immunogenicity and Biomarkers (BIB) group, the details of 
which will be included in the SRM.  Concentrations of GSK2857916 (intact ADC and 
total mAb) and cys-mcMMAF will be determined in plasma samples using the currently 
approved bioanalytical methodology.  Raw data will be archived at the bioanalytical site 
(detailed in the SRM). 
Once the plasma has been analyzed for GSK2857916 (intact ADC and total mAb) and 
cys-mcMMAF, any remaining plasma may be analyzed for other compound-related 
metabolites and the results reported under a separate GSK PTS-BIB protocol. 


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8.7. 
Genetics  
In this study, genetics may be evaluated after review by the ethical review committee 
established by GSK in accordance with Japanese ethical guidelines for human 
genome/gene analysis research. 
A 6 mL sample for blood sample for deoxyribonucleic acid (DNA) isolation will be 
collected from participants who have consented to participate in the genetics analysis 
component of the study. Participation is optional. Participants who do not wish to 
participate in the genetic research may still participate in the study. 
In the event of DNA extraction failure, a replacement genetic blood sample may be 
requested from the participant. Signed informed consent will be required to obtain a 
replacement sample unless it was included in the original consent. 
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See Appendix 4 for Information regarding genetic research. Details on processes for 
collection and shipment and destruction of these samples can be found in study manual. 
8.9. 
Immunogenicity Assessments  
Immunogenicity sample analysis will be performed under control of GSK Platform 
Technology and Sciences (PTS)-Bioanalysis Immunogenicity and Biomarkers (BIB) 
group, the details of which will be included in the SRM. 
In Part 1, serum samples for determination of anti-GSK2857916 antibodies will be taken 
from all participants in this study at the time-points specified in the SoA.   
In Part 2, serum samples for the analysis of anti-GSK2857916 antibodies will be 
collected prior to each GSK2857916 dose on PK/PD sampling days (at the same time as 
the predose GSK2857916 PK/PD samples are taken); for treatment beyond 12th doses, 
collect samples for ADA analysis prior to every 6th dose of GSK2857916 (Dose 18, Dose 
24, Dose 30, and so on, until PD).  A final ADA sample will be drawn at the EOT visit. 
Anti-GSK2857916 antibody samples will be tested for anti-GSK2857916 antibodies 
using a tiered-testing scheme consisting of validated screening, confirmation, and 
titration assays.  Briefly, all samples will be tested in the screening assay.  Samples that 
screen positive are considered potentially positive and will be tested for specificity in a 
confirmation assay.  Finally, titer values will be obtained for confirmed positive samples 
using a titration assay.  The sample results (e.g., positive or negative) and titer values 
(positive samples only) will be reported.  Samples that test positive for anti-GSK2857916 
antibodies may be further characterized in a validated neutralizing antibody assay to 
determine the neutralizing activity of the antibodies. 
The detection and characterization of antibodies to GSK2857916 will be performed using 
validated assays.  The anti-GSK2857916 antibody assay was designed to detect 
antibodies to GSK2857916, the unconjugated monoclonal antibody and the 
linker-payload portion of GSK2857916. 
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For each participant, immunogenicity results, including the incidence and titers, will be 
reported. Raw data will be archived at the bioanalytical site (detailed in the SRM). 
8.10. 
Evaluation of Anti-myeloma Activity  
Response will be assessed according to the IMWG criteria [Kumar, 2016] by the 
Investigator. 
Standard disease assessments for MM will include serum and urine laboratory tests, bone 
marrow aspirate/biopsy at the time of CR (IHC).  Evaluation will follow the guidance of 
IMWG Uniform Response Criteria for Multiple Myeloma [Kumar, 2016]. 
 
Clinical efficacy measured as ORR, which is defined as the percentage of 
participants with confirmed sCR, CR, VGPR, or PR as assessed by 2016 
recommendation of the IMWG Panel I [Kumar, 2016]. 
 
Other efficacy measures of interest (see Section 8.1). 
Disease assessment will include laboratory testing and physical examination (as indicated 
for palpable/superficial lesions), or imaging CT, MRI, PET/CT, or X-ray (as indicated).  
Laboratory-based disease assessments will be completed within 21 days prior to the first 
dose of GSK2857916 then testing will be performed every 3 weeks from C1D1.  The 
imaging will be performed up to 30 days prior to the first dose and will be repeated as 
indicated in the SoA table.  See the SoA (Section 1.3) for the schedule of anti-cancer 
activity. 
Assessments must be performed on a calendar schedule and must not be affected by dose 
interruptions/delays. 
8.11. 
Health Economics  
Not applicable. 
9. 
DATA MANAGEMENT  
For this study, data will be collected using defined eCRFs, transmitted electronically to 
the sponsor or designee and combined with data provided from other sources in a 
validated data system. 
Management of clinical data will be performed in accordance with applicable the sponsor 
or designee standards and data cleaning procedures to ensure the integrity of the data, e.g. 
removing errors and inconsistencies in the data.  AEs and concomitant medications terms 
will be coded using MedDRA and an internal validated medication dictionary, GSK 
Drug.  ECRFs, including queries and audit trails, will be retained by the sponsor or 
designee, and copies will be sent to the investigator to maintain as the investigator copy. 
When laboratory samples (i.e., hematology and clinical chemistry) are analyzed by a 
central laboratory the results will be stored in a database maintained by the central 
laboratory and transferred to the sponsor or designee at agreed times. 


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In all cases, participant initials will not be collected or transmitted to the sponsor or 
designee according to GSK policy. 
10. 
STATISTICAL CONSIDERATIONS  
This section briefly describes the planned analyses to be performed for study 207504. 
Analyses will be fully described in the Reporting and Analysis Plan (RAP). 
For Part 1, available safety data will be reviewed after the completion of DLT evaluation 
period to determine if a dose-escalation is appropriate.  Additionally, PK data will be 
reviewed after the completion of DLT evaluation period to assess PK similarity between 
Japanese and overseas populations. A primary analysis will be conducted to evaluate 
safety, efficacy and PK profiles by the data cut-off performed after both EOT and the 
completion of AE and SAE collection (i.e., 70 days after the last dose of study treatment) 
for last participant in Part 1. 
For Part 2, available safety data will be reviewed after the completion of DLT evaluation 
period per each arm to determine if the combination dose regimen is tolerable. An interim 
analysis may be conducted when the last participant within any arm in Part 2 has 
completed at least one cycle of the combination treatment to support a regulatory 
submission. A primary analysis will be conducted per arm to evaluate safety, efficacy and 
PK profiles by the data cut-off performed after both EOT and the completion of AE and 
SAE collection (i.e., 70 days after the last dose of study treatment) for last participant in 
Part 2. The later of the primary analyses for Arm A (B-Vd cohort) and Arm B (B-Pd 
cohort) in Part 2 will be the final analysis for the entire study. 
10.1. 
Statistical Hypotheses  
No formal statistical hypotheses are being tested in the study.  Analysis of the data 
obtained from the study will only utilize descriptive methods.  Statistical analyses will be 
performed separately for Part 1 and for Part 2 as well as being performed independently 
for Arm A and Arm B. 
10.2. 
Sample Size Determination  
The sample size planned for this study arises from the predefined criteria for dose 
escalation and is not driven by statistical considerations. 
The maximum number of participants for Part 1 will be up to 12 participants, 
6 participants each for 2.5 mg/kg cohort and 3.4 mg/kg cohort based on the 3 + 3 design.  
The maximum number of participants for Part 2 will be up to 12, up to 6 participants each 
for Arm A and Arm B based on the 3 + 3 design. 
10.3. 
Populations for Analyses  
For purposes of analysis, the following populations are defined.  Each of the following 
populations will be created separately for Part 1 and for Part 2 as well as being performed 
independently for Arm A and Arm B. 


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Population 
Description 
All Screened 
The ‘All Screened’ population is defined as all participants who 
sign the ICF to participate in the clinical study. Participants in this 
population will be used for screen failure summary 
All Treated 
All eligible participants who receive at least 1 dose of study 
treatment. An incorrect treatment schedule or study treatment 
administration or an early termination of treatment will not result in 
exclusion of participants from this population.  
Note: Participants with major deviations from the eligibility criteria 
affecting safety or from the treatment schedule at the DLT 
evaluation period (1 cycle: 21 days for once every 3 weeks 
schedule for Part 1 and Part 2 Arm A or 28 days for once every 4 
weeks for Part 2 Arm B) for reasons other than toxicity may be 
presented in separate tables/listings. 
DLT Evaluable 
This population enables an appropriate evaluation of study DLTs. 
It is defined as those participants fulfilling the ‘All Treated’ 
population criteria, and those who received a complete infusion in 
Cycle 1 (Part 1) or received a complete infusion of GSK2857916 
and at least 75% of planned doses of bortezomib/dexamethasone 
or pomalidomide/dexamethasone in Cycle 1 (Part 2). 
Pharmacokinetic 
Population 
Defined as those participants in the “All Treated” population from 
whom at least one PK sample is obtained and analyzed. 
Pharmacodynamic (PD) 
Population 
Defined as those participants in the “All Treated” population from 
whom at least one PD sample is obtained, analyzed, and is 
measurable. 
10.4. 
Statistical Analyses  
Data will be listed and summarized according to the GSK reporting standards and the 
Clinical Data Interchange Standards Consortium (CDISC), where applicable. Any 
deviations from, or additions to, the original analysis plan described in this protocol will 
be documented in the RAP and final study report. 
All data up to the time of study completion/withdrawal from study will be included in the 
analysis, regardless of duration of treatment. 
As the duration of treatment for a given participant will depend on efficacy and 
tolerability, the duration of follow-up will vary between participants. Consequently there 
will be no imputation for missing data. 
Demographic and baseline characteristics will be summarized separately for Part 1 and 
for Part 2 as well as being performed independently for Arm A and Arm B. 


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10.4.1. 
Safety Analyses  
The All Treated Population will be used for the analysis of safety data. All serially 
collected safety endpoints (e.g. laboratory tests, vital signs, ECGs) will be summarized 
separately for Part 1 and for Part 2 as well as being performed independently for Arm A 
and Arm B, according to the scheduled, nominal visit at which they were collected and 
across all on-treatment time points using a “worst-case” analysis. Complete details of the 
safety analyses will be provided in the RAP. 
Endpoint 
Statistical Analysis Methods 
Primary 
Adverse Events: Events will be summarized by frequency and proportion of 
total participants, by system organ class and preferred term. Separate 
summaries for Part 1 and for Part 2 as well as for Arm A and Arm B will be 
given for all AEs, treatment related AEs, SAEs and AEs leading to 
discontinuation of study treatment. AEs, if listed in the NCI-CTCAE (version 
4.03) will be summarized by the maximum grade separately for Part 1 and for 
Part 2 as well as being performed independently for Arm A and Arm B. 
Otherwise, the AEs will be summarized by maximum intensity separately for 
Part 1 and for Part 2 as well as being performed independently for Arm A and 
Arm B. 
Characteristics (e.g. number of occurrences, action taken, grade, etc.) of the 
following AEs of clinical interest will be summarized separately for Part 1 and 
for Part 2 as well as being performed independently for Arm A and Arm B: 
Corneal events, hematologic toxicities (including but not limited to 
thrombocytopenia and neutropenia), infusion related reaction etc. 
The incidence of deaths and the primary cause of death will be summarized 
separately for Part 1 and for Part 2 as well as being performed independently 
for Arm A and Arm B. 
Laboratory Events: Hematology and clinical chemistry data will be 
summarized separately for Part 1 and for Part 2 as well as being performed 
independently for Arm A and Arm B, using frequencies and proportions 
according to NCI-CTCAE Version 4.03. The evaluation of clinical laboratory 
tests will focus on selected laboratory analytes from the hematology and blood 
chemistry panel. 
Descriptive statistics (mean, standard deviation, median, range) will be used to 
summarize observed laboratory values and change from baseline in observed 
value at each scheduled visit, as appropriate. 
The worst-case- toxicity grade in hematology and chemistry result during the 
treatment will be summarized separately for Part 1 and for Part 2 as well as 
being performed independently for Arm A and Arm B. Shift tables from baseline 
to the worst toxicity grade during treatment will be provided for each laboratory 
analyte separately for Part 1 and for Part 2 as well as being performed 
independently for Arm A and Arm B. 
Further details will be provided in the RAP. 


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Endpoint 
Statistical Analysis Methods 
Other Safety 
Measures: 
Data for vital signs, ECGs and ophthalmic examination findings will be 
summarized separately for Part 1 and for Part 2 as well as being performed 
independently for Arm A and Arm B, based on predetermined criteria identified 
to be of potential clinical concern (PCI). For continuous variables, these 
summaries will include sample size, mean, median, standard deviation, 
minimum, and maximum. For categorical variables, the summaries will include 
frequencies and corresponding percentages. 
Further details will be provided in the RAP. 
10.4.1.1. 
Extent of Exposure  
The number of participants administered study treatment will be summarized separately 
for Part 1 and for Part 2 as well as being performed independently for Arm A and Arm B, 
according to the duration of therapy. 
10.4.2. 
Efficacy Analyses  
ORR is one of the secondary endpoints to measure clinical activity of this study. 
For multiple myeloma, ORR is defined as the percentage of participants with a confirmed 
PR or better (i.e., PR, VGPR, CR and sCR), according to the IMWG Response Criteria 
[Kumar, 2016], as assessed by the investigator. In addition CBR is defined as the 
percentage of participants with a confirmed MR or better (i.e., MR, PR, VGPR, CR and 
sCR), according to the IMWG Response Criteria [Kumar, 2016], as assessed by the 
investigator. 
The number and percentage of participants in the following response categories will be 
presented separately for Part 1 and for Part 2 as well as being performed independently 
for Arm A and Arm B: sCR, CR, VGPR, PR, MR, SD, progressive disease, and not 
evaluable. 
sCR+CR+VGPR+PR for ORR. 
sCR+CR+VGPR+PR+MR for CBR. 
The corresponding exact 95% CI for ORR and CBR will also be provided. Participants 
with unknown or missing response will be treated as non-responders, i.e., these 
participants will be included in the denominator when calculating percentages of 
response. 
Endpoint 
Statistical Analysis Methods 
Primary 
No primary efficacy analysis is planned in the study 


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Endpoint 
Statistical Analysis Methods 
Secondary 
Investigation of initial anti-tumor activity is a secondary objective in the study. 
The All Treated Population will be used for anti-myeloma activity analyses. 
Since this is a Phase I study, anti-myeloma activity will be evaluated based 
on clinical evidence and response criteria. If data warrant, the response data 
will be summarized separately for Part 1 (by dose level) and for Part 2 as 
well as being performed independently for Arm A and Arm B. Full details will 
be specified in the RAP. 
10.4.3. 
Immunogenicity Analyses  
For each participant, the results and titers of anti-GSK2857916 binding antibodies will be 
listed for each assessment time point. The frequency and percentage of participants with 
positive and negative results will be summarized for each assessment time and overall for 
each participant separately for Part 1 (by dose cohort) and for Part 2 as well as being 
performed independently for Arm A and Arm B. 
10.4.4. 
Pharmacokinetic Analyses  
10.4.4.1. 
Concentration-Time Data  
Linear and semi-logarithmic individual plasma concentration-time profiles and mean and 
median profiles (when applicable) will be plotted for both GSK2857916 (intact ADC and 
total mAb) and cys-mcMMAF separately for Part 1 (by dose cohort) and for Part 2 by 
Arm. 
GSK2857916 (intact ADC and total mAb) and cys-mcMMAF concentration-time data 
will be listed for each participant and summarized by descriptive statistics at each time 
point separately for Part 1 (by dose cohort) and for Part 2 as well as being performed 
independently for Arm A and Arm B. 
10.4.4.2. 
Derived Pharmacokinetic Parameters  
PK parameters will be calculated by standard non-compartmental analysis according to 
current working practices and using the currently supported version of WinNonlin. All 
calculations of non-compartmental parameters will be based on the actual sampling 
times. From the plasma concentration-time data, the following GSK2857916 (intact 
ADC, total mAb), and cys-mcMMAF PK parameters will be determined as data permit, 
for each dose of GSK2857916 and for each participant:  
1. After single dose: area under the plasma concentration-time curve (AUC(0-t), 
AUC(0-tau) and/or AUC(0-∞)), maximum observed concentration (Cmax, plasma), 
time to Cmax (tmax), last time point where the concentration is above the limit of 
quantification (tlast), systemic clearance (CL), volume of distribution at steady state 
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2. After repeat dose: concentration at end of infusion (Ceoi), concentration pre-dose 
after C3 (Ctrough), Rac (accumulation ratio) for Ceoi and Ctrough. 
Pharmacokinetic parameters will be listed, and summarized descriptively (mean, standard 
deviation, median, minimum, maximum, geometric mean, and the standard deviation, 
coefficient of variation [CV%] and 95% CI of log-transformed parameters) separately for 
Part 1 (by dose cohort) and for Part 2 by Arm. 
To assess the extent of accumulation following GSK2857916 repeat dosing, the observed 
Rac for both GSK2857916 intact ADC, total mAb, and cys-mcMMAF will be determined 
as Ceoi and Ctrough at steady-state to Ceoi and Ctrough after the first dose, respectively. 
10.4.6. 
Genetic Analyses  
Further details on genetic analyses will be addressed in Appendix 4. 
10.5. 
Interim Analyses  
10.5.1. 
Part 1  
Available safety data will be reviewed after the completion of DLT evaluation period to 
determine if a dose-escalation is appropriate.  Additionally, PK data will be reviewed 
after the completion of DLT evaluation period to assess PK similarity between Japanese 
and overseas populations. 
 
10.5.2. 
Part 2  
Available safety data will be reviewed after the completion of DLT evaluation period 
within each arm to determine if the combination dose regimen is tolerable. 
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An interim analysis may be conducted when the last participant within any arm in Part 2 
has completed at least one cycle of the combination treatment to evaluate safety, efficacy 
and PK profiles. 
10.5.3. 
Data Monitoring Committee (DMC)  
Data Monitoring Committee will not be established in the study. 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS  
11.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations  
11.1.1. 
Regulatory and Ethical Considerations  
 
This study will be conducted in accordance with the protocol and with: 
 Consensus ethical principles derived from international guidelines 
including the Declaration of Helsinki and Council for International 
Organizations of Medical Sciences (CIOMS) International Ethical 
Guidelines 
 Applicable ICH Good Clinical Practice (GCP) Guidelines 
 Applicable laws and regulations: The Ministerial Ordinance on the 
Standards for the Conduct of Clinical Trials of Medicinal Products (MHW 
Notification No.28 dated 27 Mar 1997)” and Pharmaceuticals and Medical 
Devices Act  
 
The protocol, protocol amendments, ICF, IB, and other relevant documents 
(e.g., advertisements) must be submitted to an IRB/IEC by the investigator and 
reviewed and approved by the IRB/IEC before the study is initiated.  
 
Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes 
necessary to eliminate an immediate hazard to study participants.  
 
The investigator will be responsible for the following: 
 Providing written summaries of the status of the study to the IRB/IEC 
annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/EC 
 Notifying the IRB/IEC of SAE or other significant safety findings as 
required by IRB/IEC procedures 
 Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European 
regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations. 


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GSK will submit the Clinical Trial Notification to the regulatory authorities in 
accordance with Pharmaceuticals and Medical Devices Act before conclusion of any 
contract for the conduct of the study with study sites. 
11.1.2. 
Financial Disclosure  
Investigators and sub-investigators will provide the sponsor with sufficient, accurate 
financial information as requested to allow the sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
11.1.3. 
Informed Consent  
Prior to participation in the study, the investigator should fully inform the potential 
participant and/or the participant's legally acceptable representative of the study including 
the written information. The investigator should provide the participant and/or the 
participant's legally acceptable representative ample time and opportunity to inquire 
about details of the study. The participant and/or the participant’s legally acceptable 
representative should sign and personally date the consent form. The participant may 
consider the content of the written information at home. The person, who conducted the 
informed consent discussion and the study collaborator giving supplementary 
explanation, where applicable, should sign and personally date the consent form. If an 
impartial witness is required, the witness should sign and personally date the consent 
form. The investigator should retain this signed and dated form (and other written 
information) together with the source medical records, such as clinical charts (in 
accordance with the rules for records retention, if any, at each medical institution) and 
give a copy to the participant and/or the participant’s legally acceptable representative. 
11.1.3.1. 
Informed Consent Process  
 
The investigator or his/her representative will explain the nature of the study to 
the participant or his/her legally authorized representative and answer all 
questions regarding the study. 
 
Participants must be informed that their participation is voluntary. Participants 
or their legally authorized representative will be required to sign a statement of 
informed consent that meets the requirements of 21 CFR 50, local regulations, 
ICH guidelines, Health Insurance Portability and Accountability Act (HIPAA) 
requirements, where applicable, and the IRB/IEC or study center. 
 
The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent 
must also sign the ICF. 
 
Participants must be re-consented to the most current version of the ICF(s) 
during their participation in the study. 
 
A copy of the ICF(s) must be provided to the participant or the participant’s 
legally authorized representative. 


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 
Participants who are rescreened are required to sign a new ICF. 
11.1.4. 
Data Protection  
 
Participants will be assigned a unique identifier by the sponsor. Any participant 
records or datasets that are transferred to the sponsor will contain the identifier 
only; participant names or any information which would make the participant 
identifiable will not be transferred 
 
The participant must be informed that his/her personal study-related data will be 
used by the sponsor in accordance with local data protection law. The level of 
disclosure must also be explained to the participant 
 
The participant must be informed that his/her medical records may be examined 
by Clinical Quality Assurance auditors or other authorized personnel appointed 
by the sponsor, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities. 
11.1.5. 
Committees Structure  
Safety and Efficacy Evaluation Committee will be utilized in this study to ensure external 
objective medical and/or statistical review of safety and/or efficacy issues in order to 
protect the ethical and safety interests of participants and to protect the scientific validity 
of the study. GSK can request the Safety and Efficacy Evaluation Committee to assess at 
intervals the progress of the study, the safety data, and the efficacy endpoints, and to 
make a recommendation whether to continue, modify, or stop the study if necessary. 
11.1.6. 
Dissemination of Clinical Study Data  
 
Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report.  The investigator 
will be provided reasonable access to statistical tables, figures, and relevant 
reports and will have the opportunity to review the complete study results at a 
GSK site or other mutually-agreeable location 
 
GSK will also provide the investigator with the full summary of the study 
results.  The investigator is encouraged to share the summary results with the 
study participants, as appropriate 
 
The procedures and timing for public disclosure of the protocol and results 
summary and for development of a manuscript for publication for this study will 
be in accordance with GSK Policy 
 
GSK intends to make anonymized patient-level data from this study available to 
external researchers for scientific analyses or to conduct further research that 
can help advance medical science or improve patient care. This helps ensure the 
data provided by study participants are used to maximum effect in the creation 
of knowledge and understanding. 


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11.1.7. 
Data Quality Assurance  
 
All participant data relating to the study will be recorded on printed or electronic 
CRF unless transmitted to the sponsor or designee electronically (e.g., 
laboratory data). The investigator is responsible for verifying that data entries 
are accurate and correct by physically or electronically signing the CRF 
 
The investigator must maintain accurate documentation (source data) that 
supports the information entered in the CRF 
 
The investigator must permit study-related monitoring, audits, IRB/IEC review, 
and regulatory agency inspections and provide direct access to source data 
documents 
 
Monitoring details describing strategy (e.g., risk-based initiatives in operations 
and quality such as Risk Management and Mitigation Strategies and Analytical 
Risk-Based Monitoring), methods, responsibilities and requirements, including 
handling of noncompliance issues and monitoring techniques (central, remote, 
or on-site monitoring) are provided in the Monitoring Plan. 
 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data 
 
The sponsor assumes accountability for actions delegated to other individuals 
(e.g., Contract Research Organizations) 
 
Study monitors will perform ongoing source data verification to confirm that 
data entered into the CRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants 
are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements 
 
Records and documents, including signed ICF, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
Clinical Study Report (CSR)/ equivalent summary unless local regulations or 
institutional policies require a longer retention period. No records may be 
destroyed during the retention period without the written approval of the 
sponsor. No records may be transferred to another location or party without 
written notification to the sponsor. 
11.1.8. 
Source Documents  
 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site 
 
Data reported on the CRF or entered in the eCRF that are transcribed from 
source documents must be consistent with the source documents or the 
discrepancies must be explained. The investigator may need to request previous 
medical records or transfer records, depending on the study. Also, current 
medical records must be available 


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 
Definition of what constitutes source data can be found in SRM. 
11.1.9. 
Study and Site Closure  
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study 
supplies have been collected and a study-site closure visit has been performed. 
The investigator may initiate study-site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the sponsor or investigator may include 
but are not limited to: 
 
Failure of the investigator to comply with the protocol, the requirements of the 
IRB/IEC or local health authorities, the sponsor's procedures, or GCP guidelines 
 
Inadequate recruitment of participants by the investigator 
 
Discontinuation of further study treatment development 
11.1.10. 
Publication Policy  
 
The results of this study may be published or presented at scientific meetings. If 
this is foreseen, the investigator agrees to submit all manuscripts or abstracts to 
the sponsor before submission. This allows the sponsor to protect proprietary 
information and to provide comments  
 
The sponsor will comply with the requirements for publication of study results. 
In accordance with standard editorial and ethical practice, the sponsor will 
generally support publication of multicenter studies only in their entirety and not 
as individual site data. In this case, a coordinating investigator will be 
designated by mutual agreement 
 
Authorship will be determined by mutual agreement and in line with 
International Committee of Medical Journal Editors authorship requirements 
11.1.11. 
Study Period  
Study period is included in Exhibit 3. 
11.1.12. 
Study Administrative Structure  
Sponsor information is included in Exhibit 1. List of Medical Institutions and 
Investigators is included in Exhibit 2. 
 


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11.2. 
Appendix 2: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting  
11.2.1. 
Definition of AE  
AE Definition 
 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study treatment, whether or not considered 
related to the study treatment. 
 
NOTE: An AE can therefore be any unfavorable and unintended sign (including 
an abnormal laboratory finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a study treatment. 
 
Events Meeting the AE Definition 
 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease). 
 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
 
New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study. 
 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae. 
 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not 
be reported as an AE or SAE. Such instances will be captured in the efficacy 
assessments. However, the signs, symptoms, and/or clinical sequelae resulting 
from lack of efficacy will be reported as AE or SAE if they fulfill the definition of 
an AE or SAE. 
 
Events NOT Meeting the AE Definition  
 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the participant’s condition. 


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 
The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that 
leads to the procedure is the AE. 
 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
11.2.2. 
Definition of SAE  
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
A SAE is defined as any untoward medical occurrence that, at any dose: 
o Results in death 
o Is life-threatening 
The term 'life-threatening' in the definition of 'serious' refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AE. If a 
complication prolongs hospitalization or fulfills any other serious criteria, the event is 
serious. When in doubt as to whether “hospitalization” occurred or was necessary, the 
AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 
Results in persistent disability/incapacity 
 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 


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Is a congenital anomaly/birth defect 
Other situations: 
 
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
Is associated with liver injury and impaired liver function defined as: 
 
ALT 3 x ULN and total bilirubin* 2 x ULN (>35% direct), or 
 
ALT 3 x ULN and INR** >1.5. 
* Serum bilirubin fractionation should be performed if testing is available; if 
unavailable, measure urinary bilirubin via dipstick.  If fractionation is unavailable and 
ALT 3 x ULN and total bilirubin 2 x ULN, then the event is still to be reported as an 
SAE. 
** INR testing not required per protocol and the threshold value does not apply to 
participants receiving anticoagulants.  If INR measurement is obtained, the value is to 
be recorded on the SAE form. 
Refer to Appendix 5 for liver chemistry follow-up procedures. 
11.2.3. 
Definition of Cardiovascular Events  
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs: 
 
Myocardial infarction/unstable angina 
 
Congestive heart failure 
 
Arrhythmias 
 
Valvulopathy 
 
Pulmonary hypertension 
 
Cerebrovascular events/stroke and transient ischemic attack 


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 
Peripheral arterial thromboembolism 
 
Deep venous thrombosis/pulmonary embolism 
 
Revascularization 
11.2.4. 
Recording and Follow-Up of AE and SAE  
AE and SAE Recording 
 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
 
The investigator will then record all relevant AE/SAE information in the CRF. 
 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK /AE/SAE CRF page. 
 
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to GSK. 
 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis 
(not the individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to 1 of the following categories:  
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated.  
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting age-
appropriate instrumental ADL*.  
Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL**.  
Grade 4: Life-threatening consequences; urgent intervention indicated.  
Grade 5: Death related to AE. 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc. 
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not 
bedridden. 


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Corneal events associated with GSK2857916 will be graded according to the 
grading scale provide in Appendix 7. 
 
Assessment of Causality 
 
The investigator is obligated to assess the relationship between study treatment 
and each occurrence of each AE/SAE. 
 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot 
be ruled out. 
 
The investigator will use clinical judgment to determine the relationship. 
 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study treatment 
administration will be considered and investigated. 
 
The investigator will also consult the IB and/or Product Information, for marketed 
products, in his/her assessment. 
 
For each AE/SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE/SAE and has provided an assessment of causality. 
 
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK. 
 
The investigator may change his/her opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality 
assessment. 
 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE and SAE 
 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK 
to elucidate the nature and/or causality of the AE or SAE as fully as possible. This 
may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
 
If a participant dies during participation in the study or during a recognized 
follow-up period, the investigator will provide GSK with a copy of any post-
mortem findings including histopathology. 
 
New or updated information will be recorded in the originally completed CRF. 


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 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
 
11.2.5. 
Reporting of SAE to GSK  
SAE Reporting to GSK via Electronic Data Collection Tool 
 
The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool. 
 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) in order to report the event within 24 hours. 
 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
 
The investigator or medically-qualified sub-investigator must show evidence 
within the eCRF (e.g., check review box, signature, etc.) of review and verification 
of the relationship of each SAE to IP/study participation (causality) within 72 
hours of SAE entry into the eCRF. 
 
After the study is completed at a given site, the electronic data collection tool will 
be taken off-line to prevent the entry of new data or changes to existing data. 
 
If a site receives a report of a new SAE from a study participant or receives 
updated data on a previously reported SAE after the electronic data collection tool 
has been taken off-line, then the site can report this information on a paper SAE 
form (see next section) or to the medical monitor/SAE coordinator by telephone 
 
Contacts for SAE reporting can be found in SRM. 
 
SAE Reporting to GSK via Paper CRF 
 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit 
this information to the SAE coordinator. Detail provided in the SRM. 
 
In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE CRF pages within the designated reporting time 
frames. 
 
Contacts for SAE reporting can be found in SRM. 


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11.3. 
Appendix 3: Contraceptive Guidance and Collection of 
Pregnancy Information  
11.3.1. 
Definitions:  
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile (see below). 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study treatment, additional evaluation should be 
considered. 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
 
Documented hysterectomy 
 
Documented bilateral salpingectomy 
 
Documented bilateral oophorectomy 
For individuals with permanent infertility due to an alternate medical cause other 
than the above, (e.g., mullerian agenesis, androgen insensitivity), investigator 
discretion should be applied to determining study entry. 
Note: Documentation can come from the site personnel’s: review of the 
participant’s medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause.  
 
A high FSH level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or 
hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, confirmation with more than one FSH 
measurement is required.  
 
Females on HRT and whose menopausal status is in doubt will be required to 
use one of the non-estrogen hormonal highly effective contraception methods 
if they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before 
study enrollment. 
11.3.2. 
Contraception Guidance:  
 
CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE: 


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 
Highly Effective Methodsb That Have Low User Dependency 
 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
 
Intrauterine device (IUD) 
 
Intrauterine hormone-releasing system (IUS)c 
 
Bilateral tubal occlusion 
 
Vasectomized partner 
Note: Vasectomized partner is a highly effective contraceptive method provided that 
the partner is the sole sexual partner of the woman of childbearing potential and the 
absence of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. Spermatogenesis cycle is approximately 90 days. 
 
Highly Effective Methodsb That Are User Dependent 
 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationc 
 
oral 
 
intravaginal 
 
transdermal 
 
injectable 
 
Progestogen-only hormone contraception associated with inhibition of ovulationc 
 
oral 
 
injectable 
 
Sexual abstinence 
Note: Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with 
the study treatment. The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the study and the preferred and usual lifestyle of the 
participant. 
l. 
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
m. Failure rate of <1% per year when used consistently and correctly. Typical use failure rates differ from those 
when used consistently and correctly. 
n. 
Male condoms must be used in addition to hormonal contraception.  If locally required, in accordance with 
Clinical Trial Facilitation Group (CTFG) guidelines, acceptable contraceptive methods are limited to those 
which inhibit ovulation as the primary mode of action. 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), withdrawal (coitus interruptus), 
spermicides only, and lactational amenorrhoea method (LAM) are not acceptable methods of contraception for this 
study. Male condom and female condom should not be used together (due to risk of failure with friction). 
 
Of contraceptive methods defined in the protocol Appendix 3, Contraceptive Methods 
Approved in this Study, the followings are not approved in Japan as contraceptive 
method. 


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Highly Effective Methods That Have Low User Dependency 
 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation 
Highly Effective Methods That Are User Dependent 
 
Combined (estrogen- and progestogen-containing) hormonal contraception 
associated with inhibition of ovulation  
 
intravaginal 
 
transdermal 
 
injectable 
 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
 
oral 
 
injectable 
 
11.3.3. 
Collection of Pregnancy Information:  
Male participants with partners who become pregnant 
 
Investigator will attempt to collect pregnancy information on any male participant’s 
female partner of a male study participant who becomes pregnant while participating 
in this study and for 6 months following the last dose of GSK2857916, 4 months 
following the last dose of bortezomib (only Part 2 Arm A), and 4 weeks following 
the last dose of pomalidomide (only Part 2 Arm B), whichever is longest, by 
telephone for WOCBP partners only. This applies only to male participants who 
receive study treatment. 
 
After obtaining the necessary signed informed consent from the pregnant female 
partner directly, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 24 hours of learning of the partner’s 
pregnancy.  
 
The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to GSK. 
 
Generally, follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of fetal 
status (presence or absence of anomalies) or indication for procedure.  
Female Participants who become pregnant 
 
Investigator will collect pregnancy information on any female participant, who 
becomes pregnant while participating in this study and for 4 months following the 
last dose of GSK2857916, 7 months following the last dose of bortezomib (only 


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Part 2 Arm A), and 4 weeks following the last dose of pomalidomide (only Part 2 
Arm B), whichever is longest.  
 
Information will be recorded on the appropriate form and submitted to GSK within 
24 hours of learning of a participant's pregnancy.  
 
Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow up information on participant and neonate, which will 
be forwarded to GSK Generally, follow-up will not be required for longer than 6 to 
8 weeks beyond the estimated delivery date.   
 
Any termination of pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure.  
 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
SAE.  
 
A spontaneous abortion is always considered to be an SAE and will be reported as 
such.  
 
Any SAE occurring as a result of a post-study pregnancy which is considered 
reasonably related to the study treatment by the investigator, will be reported to GSK 
as described in Appendix 3. While the investigator is not obligated to actively seek 
this information in former study participants, he or she may learn of an SAE through 
spontaneous reporting.  
Any female participant who becomes pregnant while participating will discontinue 
study treatment or be withdrawn from the study 


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11.4. 
Appendix 4: Genetics  
USE/ANALYSIS OF DNA 
In this study, genetics may be evaluated after review by the ethical review committee 
established by GSK in accordance with Japanese ethical guidelines for human 
genome/gene analysis research, see Section 8.7 for further details on genetic research. 
 
Genetic variation may impact a participant’s response to study treatment, 
susceptibility, severity and progression of disease. Variable response to study 
treatment may be due to genetic determinants that impact drug absorption, 
distribution, metabolism, and excretion; mechanism of action of the drug; disease 
etiology; and/or molecular subtype of the disease being treated. Therefore, where 
local regulations and IRB/IEC allow, a 6 mL of blood sample will be collected for 
DNA analysis 
 
DNA samples will be used for research related to Multiple Myeloma and related 
diseases. They may also be used to develop tests/assays including diagnostic tests) 
related to GSK2857916 or study treatments of this drug class, and Multiple 
Myeoloma. Genetic research may consist of the analysis of one or more candidate 
genes or the analysis of genetic markers throughout the genome or analysis of the 
entire genome (as appropriate) 
 
DNA samples will be analyzed for describe planned analyses. Additional analyses 
may be conducted if it is hypothesized that this may help further understand the 
clinical data.  
 
The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to GSK2857916 or study treatments of this class. The 
results of genetic analyses may be reported in the clinical study report or in a 
separate study summary. 
 
The results of genetic analyses will not be disclosed to each participant because they 
may not directly relevant to the treatment strategy and may stress out the participant 
and his/her family. 
 
Where participants withdraw the consent to participate in the genetics analysis 
component of the study after samples have been taken from them, the samples will 
not be used for new analyses and will be destroyed.  Where participants’ genetic data 
have been analyzed before they withdraw the consent to the genetics analysis 
component, the results will be used.  In addition, where participants’ genetic data 
have been obtained but have not been analyzed yet when they withdraw they 
withdraw the consent to the genetics analysis component, the data will not be used 
for any purposes. 
 
The sponsor will store the DNA samples in a secure storage space at 
approximately -80℃ with adequate measures to protect confidentiality.  
Please refer to Gx Sample Storage Facility of Exhibit 1 for information about the 
storage facility. 


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 
The samples will be retained while research on GSK2857916 (or study treatments of 
this class) or Multiple Myeloma continues but no longer than 15 years after the last 
subject last visit or other period as per local requirements. 
 
The samples will be destroyed appropriately according to the procedures of the 
storage facility (see Exhibit 1), under administration of the sponsor.  The sponsor 
will be informed of sample destruction. 


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11.5. 
Appendix 5: Liver Safety: Required Actions and Follow-up 
Assessments and Study Treatment Rechallenge Guidelines  
Phase I liver chemistry stopping criteria have been designed to assure participant’s safety 
and to evaluate liver event etiology. 
Phase I liver chemistry stopping criteria and required follow up assessments  
Liver Chemistry Stopping Criteria – Liver Stopping Event 
ALT-absolute 
ALT≥5xULN 
ALT Increase 
ALT≥3xULN persists for ≥4 weeks 
Bilirubin1, 2 
ALT≥3xULN and bilirubin≥2xULN (>35% direct bilirubin) 
INR2 
ALT≥3xULN and INR>1.5 
Cannot 
Monitor 
ALT≥3xULN and cannot be monitored weekly for 4 weeks 
Symptomatic3 
ALT≥3xULN associated with symptoms (new or worsening) believed to be 
related to liver injury or hypersensitivity 
Required Actions and Follow up Assessments following ANY Liver Stopping Event 
Actions 
Follow Up Assessments 
 Immediately discontinue study treatment 
 Report the event to GSK within 24 hours 
 Complete the liver event form and complete 
SAE data collection tool if the event also meets 
the criteria for an SAE2 
 Perform liver event follow up assessments  
 Monitor the participant until liver chemistries 
resolve, stabilise, or return to within baseline 
(see MONITORING below) 
MONITORING: 
If ALT≥3xULN AND total bilirubin≥2xULN or 
INR>1.5:  
 Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin and INR) and 
perform liver event follow up assessments 
within 24 hrs 
 Viral hepatitis serology4 
 Obtain INR and recheck with each 
liver chemistry assessment until the 
transaminases values show 
downward trend 
 Blood sample for pharmacokinetic 
(PK) analysis and a blood sample for 
 
 within 70 days after last 
dose of GSK28579165 
 Serum creatine phosphokinase 
(CPK) and lactate dehydrogenase 
(LDH), gamma glutamyltransferase 
(GGT), glutamate dehydrogenase 
(GLDH), and serum albumin 
 Fractionate bilirubin, if total 
bilirubin2xULN 
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 Monitor participants twice weekly until liver 
chemistries resolve, stabilise or return to within 
baseline 
 A specialist or hepatology consultation is 
recommended 
For all other criteria (bilirubin <2xULN and 
INR≤1.5):  
 Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin and INR) and 
perform liver event follow up assessments 
within 24-72 hrs  
 Monitor participants weekly until liver 
chemistries resolve, stabilize or return to within 
baseline 
RESTART/RECHALLENGE:  
 Restart/rechallenge is allowed per protocol 
but do not resume study treatment unless 
GSK approval is granted; If 
restart/rechallenge is not granted, permanently 
discontinue study treatment and continue 
participant in the study for any protocol 
specified follow up assessments. Refer to 
Restart/Rechallenge guidelines in Appendix 5. 
 Obtain complete blood count with 
differential to assess eosinophilia 
 Record the appearance or worsening 
of clinical symptoms of liver injury, or 
hypersensitivity, on the liver event 
form 
 Record use of concomitant 
medications on the concomitant 
medications report form including 
acetaminophen, herbal remedies, 
recreational drugs and other over the 
counter medications. 
 Record alcohol use on the liver event 
alcohol intake form 
If ALT≥3xULN AND total 
bilirubin≥2xULN or INR>1.5 obtain the 
following in addition to the assessments 
listed above: 
 Anti-nuclear antibody, anti-smooth 
muscle antibody, Type 1 anti-liver 
kidney microsomal antibodies, and 
quantitative total immunoglobulin G 
(IgG or gamma globulins) 
 Serum acetaminophen adduct assay 
should be conducted (where 
available) to assess potential 
acetaminophen contribution to liver 
injury unless acetaminophen use is 
very unlikely in the preceding week. 
(e.g., where the participant has been 
resident in the clinical unit 
throughout) 
 Liver imaging (ultrasound, magnetic 
resonance, or computerised 
tomography) to evaluate liver 
disease; complete Liver Imaging form 
 Liver biopsy may be considered and 
discussed with local specialist if 
available, for instance: 
o In participants when serology 
raises the possibility of 
autoimmune hepatitis (AIH) 


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o In participants when suspected 
drug-induced liver injury (DILI) 
progresses or fails to resolve on 
withdrawal of study treatment 
o In participants with acute or 
chronic atypical presentation 
 If liver biopsy conducted complete 
liver biopsy form. 
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that participant if ALT  3xULN and bilirubin  2xULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable urinary 
bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury.  
2. All events of ALT  3xULN and total bilirubin  2xULN (>35% direct bilirubin) or ALT  3xULN and INR>1.5, 
which may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE (excluding studies of 
hepatic impairment or cirrhosis); and the threshold value stated will not apply to participants receiving 
anticoagulants. 
3. New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, rash or 
eosinophilia). 
4. Includes: Hepatitis A IgM antibody; Hepatitis B surface antigen and Hepatitis B Core Antibody (IgM); Hepatitis C 
RNA; Cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain 
heterophile antibody or monospot testing); Hepatitis E IgM antibody or Hepatitis E RNA 
5. PK sample and associated 
 sample may not be required for participants known to be receiving placebo or 
non-GSK comparator treatments. Record the date/time of the PK/
blood sample draw and the date/time of 
the last dose of study treatment prior to blood sample draw on the CRF. If the date or time of the last dose is 
unclear, provide the participant’s best approximation. If the date/time of the last dose cannot be approximated OR 
a PK
sample cannot be collected in the time period indicated above, do not obtain a PK/
 sample. 
Instructions for sample handling and shipping are in the SRM 
Phase I liver chemistry stopping criteria and required follow up assessments 
Liver Chemistry Increased Monitoring Criteria and Actions with Continued Study 
Treatment Liver Monitoring Event 
Criteria 
Actions 
ALT3xULN but <5xULN and total bilirubin 
<2xULN or INR≤1.5, without symptoms 
believed to be related to liver injury or 
hypersensitivity and who can be monitored 
weekly for 4 weeks 
 Notify the Medical Monitor within 24 hours of 
learning of the abnormality to discuss 
participant safety 
 Participant can continue study treatment 
 Participant must return weekly for repeat liver 
chemistries (ALT, AST, alkaline phosphatase, 
total bilirubin and INR) until they resolve, 
stabilise or return to within baseline  
 If at any time participant meets the liver 
chemistry stopping criteria, proceed as 
described above 
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 If, after 4 weeks of monitoring, ALT<3xULN 
and total bilirubin<2xULN and INR≤1.5, 
monitor participants twice monthly until liver 
chemistries resolve or return to within baseline. 
11.5.1. 
Liver Safety Drug Restart or Rechallenge Guidelines  
A participant who met liver chemistry stopping criteria cannot resume study treatment 
unless all of the following conditions are met: 
 
GSK approval is granted (as described below) 
 
IRB/IEC approval is obtained 
 
Separate ICF for study treatment restart/rechallenge is signed by the participant and 
participant is informed of any associated risks 
If GSK approval to restart/rechallenge the participant with study intervention is not 
granted, then the participant must permanently discontinue study treatment and may 
continue in the study for protocol-specified follow-up assessments. 
11.5.1.1. 
Rechallenge Following Liver Stopping Events that are Possibly Related 
to Study Treatment  
Following drug-induced liver injury (DILI), drug rechallenge is associated with a 13% 
mortality across all drugs in prospective studies [Andrade, 2009]. Clinical outcomes 
vary by drug with nearly 50% fatality with halothane readministered within 1 month of 
initial injury.  However, some drugs seldom result in recurrent liver injury or fatality.   
Risk factors for a fatal drug rechallenge outcome include: 
 
Hypersensitivity with initial liver injury (e.g., fever, rash, eosinophilia) [Andrade, 
2009] 
 
Jaundice or bilirubin >2 x ULN with initial liver injury (direct bilirubin >35% of 
total) 
 
Ongoing severe liver injury defined by: ALT ≥3 x ULN, bilirubin ≥2 x ULN (direct 
bilirubin >35% of total), or INR >1.5 
SAE or fatality has been observed with drug rechallenge [Hunt, 2010; Papay, 2009] 
Evidence of drug-related preclinical liability (e.g., reactive metabolites; mitochondrial 
impairment) [Hunt, 2010] 
Rechallenge refers to resuming study treatment following study treatment induced liver 
injury (DILI).  Because of the risks associated with rechallenge after DILI this should 
only be considered for a participant for whom there is compelling evidence of benefit 
from a critical or life-saving medicine, there is no alternative approved medicine 
available, and a benefit:risk assessment of rechallenge is considered to be favorable. 


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Approval by GSK for rechallenge with study treatment can be considered where: 
 
The Principal Investigator requests consideration of rechallenge with study treatment 
for a participant who is receiving compelling benefit with study treatment that 
exceeds risk, and no effective alternative therapy is available.   
 
IRB/IEC approval for rechallenge with study treatment must be obtained.   
If the rechallenge is approved by GSK in writing 
 
The participant must be provided with a clear description of the possible benefits and 
risks of study treatment administration, including the possibility of recurrent, more 
severe liver injury or death.   
 
The participant must also provide signed informed consent specifically for the 
rechallenge with study treatment. Documentation of informed consent must be 
recorded in the study file.   
 
Study treatment must be administered at the dose specified by GSK. 
 
Participants approved by GSK for rechallenge with study treatment must return to 
the study site twice a week for liver chemistry tests until stable liver chemistries have 
been demonstrated and then standard laboratory monitoring may resume as per 
protocol. 
 
If after study treatment rechallenge, participant meets protocol-defined liver 
chemistry stopping criteria, study treatment should be permanently discontinued.  
 
Medical Monitor and the IRB/IEC as required, must be informed of the participant’s 
outcome following study treatment rechallenge.  
 
GSK to be notified of any AEs, as per Section 11.2. 
11.5.1.2. 
Restart Following Transient Resolving Liver Stopping Events NOT 
Related to Study Treatment  
Restart refers to resuming study treatment following liver stopping events in which there 
is a clear underlying cause (other than DILI) of the liver event (e.g., biliary obstruction, 
pancreatic events, hypotension, and acute viral hepatitis).  Furthermore, restart is not 
permitted following liver stopping event when the underlying cause was aoclhol-related 
hepatitis. 
Approval by GSK for study treatment restart can be considered where: 
 
Principal Investigator requests consideration for study treatment restart if liver 
chemistries have a clear underlying cause (e.g., biliary obstruction, hypotension and 
liver chemistries have improved to normal or are within 1.5 x baseline and ALT 
<3 x ULN). 
 
Possible study treatment-related liver injury has been excluded by the Principal 
Investigator and the study team. This includes the absence of markers of 
hypersensitivity (otherwise unexplained fever, rash, eosinophilia). Where a study 
treatment has an identified genetic marker associated with liver injury (e.g., 
lapatinib, abacavir, amoxicillin/clavulanate), the presence of the marker should be 


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excluded. If study treatment-related liver injury cannot be excluded, the guidance on 
rechallenge as stated in previous section will apply. 
 
There is no evidence of alcoholic hepatitis. 
 
IRB/IEC approval of study treatment restart must be obtained, as required. 
If restart of study treatment is approved by GSK in writing,  
 
The participant must be provided with a clear description of the possible benefits and 
risks of study treatment administration including the possibility of recurrent, more 
severe liver injury or death. 
 
The participant must also provide signed informed consent specifically for the study 
treatment restart. Documentation of informed consent must be recorded in the study 
file. 
 
Study treatment must be administered at the dose specified by GSK. 
 
Participants approved by GSK for restarting study treatment must return to the study 
site once a week for liver chemistry tests until stable liver chemistries have been 
demonstrated and then laboratory monitoring may resume as per protocol. 
 
If participant meets protocol-defined liver chemistry stopping criteria after study 
treatment restart, study treatment should be permanently discontinued. 
 
Medical Monitor and the IRB/IEC must be informed of the participant’s outcome 
following study treatment restart. 
 
GSK must be notified of any AEs, as per Section 11.2. 


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CCI - This section contained Clinical Outcome Assessment data collection questionnaires or indices, which are protected by third party copyright 
laws and therefore have been excluded.


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11.7. 
Appendix 7: Corneal Event Severity Grading and Mitigation 
Strategy  
In order to minimize the corneal toxicity, prophylactic preservative-free artificial tears 
should be administered in each eye at least 4 to 8 times daily beginning on C1D1 until the 
EOT.  In the event of ocular symptoms (e.g., dry eyes), the use of artificial tears may be 
increased up to every 2 hours as needed.  Corticosteroid eye drops are not required but 
can be used if clinically indicated per discretion of an eye-care specialist.  Allow at least 
5 to 10 minutes between administration of artificial tears and steroid eye drops (if 
administered together).  If steroid eye drops are deemed medically necessary and 
prescribed, intraocular pressure must be monitored if used for more than 7 days. 
While not yet clinically demonstrated, it is theoretically possible that the application of a 
cooling eye mask during GSK2857916 administration, and in the first few hours after 
infusion may subsequently decrease ocular side effects.  On the day of infusion at the 
discretion of the participant and the investigator, the following may be considered:  
 
Beginning with the start of each GSK2857916 infusion, participants may apply 
cooling eye masks to their eyes for approximately 1 hour or as much as tolerated. 
 
Participants may continue using the cooling eye mask beyond the first hour for up to 
4 hours.  Further use beyond 4 hours is at the participant’s discretion. 
Participants must avoid the use of contact lenses while the participant is receiving 
GSK2857916.  Contact lens use may be restarted after an ophthalmologist confirms there 
are no other contraindications.  Use of bandage contact lenses is permitted during study 
treatment as directed by the treating eye care specialist. 
An ophthalmology consult is required for all participants who develop signs or symptoms 
of corneal toxicity or require steroid eye drops for more than 7 days.  
A summary of prophylactic interventions for corneal events associated with 
GSK2857916 is provided in Table 36.  The severity of corneal events associated with 
GSK2857916 and related to ophthalmic exam findings or visual acuity will be also 
graded using the scale provided in Table 37.  The severity of the other corneal events will 
be graded utilizing the NCI-CTCAE.  Additional guidance on grading visual acuity 
changes provided in Table 38. 


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Table 36 
Prophylactic Measures for Corneal Events Associated with 
GSK2857916 a 
Prophylactic 
Measurea 
Dose and Administration 
Timing 
Preservative-free 
artificial tears 
Administer in each eye at least 4 
to 8 times four times daily 
Administer daily beginning on Cycle 1 
Day 1 until EOT. 
Cooling eye mask 
May apply cooling eye mask to 
both eyes for approximately 
1 hour or as much as tolerated  
During GSK2857916 infusion 
administration in the first hour for up to 
4 hours, as tolerated 
a 
Dose modifications and treatment for ocular toxicities are discussed in Section 6.7 
Table 37 
Grading Scale for Corneal Events Associated with GSK2857916 a 
Measure 
Grade 1 
Grade 2 
Grade 3  
Grade 4 
Ophthalmic 
exam 
findings 
Mild superficial 
keratopathy 
(change from 
baseline) 
 
Moderate punctate 
keratopathy 
and/or 
Mild/patchy 
microcysts 
and/or 
Mild/patchy Epithelial 
or stromal edema 
and/or 
Sub-epithelial haze 
(peripheral)  
and/or 
Active stromal opacity 
(peripheral) 
Severe punctate 
keratopathy 
and/or 
Diffuse microcysts 
and/or 
Diffuse Epithelial or 
stromal edema 
and/or 
Sub-epithelial haze 
(central)  
and/or 
Active stromal opacity 
(central) 
Corneal ulcer 
Visual 
Acuity b 
Change of 1 line 
from baseline c 
Change of 2-3 lines 
from baseline and not 
worse than 20/200 c 
Change of more than 3 
lines from baseline and 
not worse than 20/200 c 
Worse than 
Vision 20/200 c 
Note: Sites will be provided with standardized guidance for grading ophthalmic findings. 
o. 
Grading is based on most severe finding.  If eyes differ in severity, GSK grading should be based on the more 
severe eye. 
p. 
Change in visual acuity should be due to corneal findings associated with GSK2857916.  If change in vision is for 
reason other than corneal findings, ophthalmic exam findings will drive event grading. 
q. 
The change in visual acuity by Snellen chart is shown in this table.  See Table 38 for additional guidance on how 
to grade changes in Landolt ring visual acuity depending on baseline vision.  If a participant has a baseline visual 
acuity of 20/200 (0.1 for Landolt ring visual acuity) or worse in an eye, ophthalmic exam findings will drive event 
grading. 


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Table 38 
Additional Guidance on Grading Based on Changes in Visual Acuity 
(Landolt Ring Chart) 
Baseline Vision 
(best corrected) 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
1.0 
0.7 – 0.9 
0.5 – 0.6 
0.1 – 0.4 
Worse than 0.1 
0.9 
0.6 – 0.8 
0.5 
0.1 – 0.4 
Worse than 0.1 
0.8 
0.6 – 0.7 
0.4 – 0.5 
0.1 – 0.3 
Worse than 0.1 
0.7 
0.5 – 0.6 
0.4 
0.1 – 0.3 
Worse than 0.1 
0.6 
0.4 – 0.5 
0.3 
0.1 – 0.2 
Worse than 0.1 
0.5 
0.4 
0.3 
0.1 – 0.2 
Worse than 0.1 
0.4 
0.3 
0.2 
0.1 
Worse than 0.1 
0.3 
0.2 
NA 
0.1 
 
Worse than 0.1 
0.2 
NA 
0.1 
NA 
Worse than 0.1 


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11.8. 
Appendix 8: Modified Diet in Renal Disease (MDRD) Formula  
The MDRD formula for calculating the eGFR is as follows: 
eGFR = 175 × (Scr)-1.154 × (Age)-0.203 × (0.742 if female) × (0.808 if Japanese) 
GFR is expressed in mL/min/1.73 m2, SCr is serum creatinine expressed in mg/dL, and 
age is expressed in years. 
The link below will auto-calculate the creatinine clearance: http://nephron.org/cgi-
bin/MDRD_GFR/cgi 


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11.9. 
Appendix 9: International Myeloma Working Group Uniform 
Response Criteria for Multiple Myeloma  
Anti-tumor activity will be assessed according to the following criteria [Kumar, 2016]. 
Response 
International Myeloma Working Group (IMWG) Criteria 
sCR (stringent CR) 
CR as defined below plus normal free light chain (FLC) ratio and absence of 
clonal cells in bone marrow biopsy by immunohistochemistory (κ/λ ratio ≤ 4:1 
or ≥ 1:2 for κ and λ patients, respectively, after counting ≥ 100 plasma cells 
[PCs]). 
CR (complete response) 
Negative immunofixation on the serum and urine and disappearance of any 
soft tissue plasmacytomas and < 5% PCs in bone marrow aspirates. 
VGPR (very good partial response) 
 
Serum and urine M-protein detectable by immunofixation but not on 
electrophoresis. 
or 
 
≥ 90% reduction in serum M-protein plus urine M-protein level 
< 100 mg per 24 h. 
PR (partial response) 
 
≥ 50% reduction of serum M-protein plus reduction in 24 h urinary 
M-protein by ≥ 90% or to < 200 mg per 24 h. 
 
If the serum and urine M-protein are unmeasurable, a ≥ 50% decrease 
in the difference between involved and uninvolved FLC levels is 
required in place of the M-protein criteria. 
 
If serum and urine M-protein are unmeasurable, and serum-free light 
assay is also unmeasurable, ≥ 50% reduction in PCs is required in 
place of M-protein, provided baseline bone marrow PC percentage was 
≥ 30%. 
 
In addition to the above listed criteria, if present at baseline, a ≥ 50% 
reduction in the size (sum of the products of the maximal perpendicular 
diameters of measured lesions [SPD]) of soft tissue plasmacytomas is 
also required. 
MR (minimal response) 
 
≥ 25% but ≤ 49% reduction of serum M-protein and reduction in 24-h 
urine M-protein by 50-89%. 
 
In addition to the above listed criteria, if present at baseline, a ≥ 50% 
reduction in the size (SPD) of soft tissue plasmacytomas is also 
required. 
SD (stable disease) 
Not meeting criteria for CR, VGPR, PR, MR, or PD. 
PD (progressive disease) 
Any one or more of the following criteria: 
 
Increase of ≥ 25% from lowest confirmed response value in one or 
more of the following criteria: 
➢ Serum M-protein (absolute increase must be ≥ 0.5 g/dL); 
Serum M-protein increase ≥ 1 g/dL, if the lowest M component was 
≥ 5 g/dL); 
➢ 
Urine M-protein (absolute increase must be ≥ 200 mg/24 h); 
➢ In patients without measurable serum and urine M-protein levels, 
the difference between involved and uninvolved FLC levels 
(absolute increase must be ≥ 10 mg/dL); 
➢ In patients without measurable serum and urine M-protein levels 
and without measurable involved FLC levels, bone marrow PC 
percentage irrespective of baseline status (absolute increase must 
be ≥ 10%); 
 
Appearance of a new lesion(s), ≥ 50% increase from nadir in SPD of 
> 1 lesion, or ≥ 50% increase in the longest diameter of a previous 
lesion > 1 cm in short axis; 
 
≥ 50% increase in circulating PCs (minimum of 200 cells per μL) if this 
is the only measure of disease. 


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11.10. 
Appendix 10: Abbreviations and Trademarks  
ADA 
Anti-drug antibodies 
ADC 
Antibody drug conjugate 
ADCC 
Antibody-dependent cell-mediated cytotoxicity 
ADCP 
Antibody-dependent cellular phagocytosis 
ADL 
Activity of daily living 
AE 
Adverse Event 
AESI 
Adverse event of special interest 
AIH 
Autoimmune hepatitis 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
APRIL 
A proliferation-inducing ligand 
ASCT 
Autologous stem-cell transplantation 
AST 
Aspartate aminotransferase 
AUC 
Area under the curve 
AV 
Atrioventricular 
BAFF 
B-cell-activating factor belonging to the TNF family 
BCMA 
B-cell maturation antigen 
BIB 
Bioanalysis Immunogenicity and Biomarkers 
BM 
Bone marrow 
BMI 
Body mass index 
BNP 
B-type natriuretic peptide 
Bor/Dex 
Bortezomib and dexamethasone 
BP 
Blood Pressure 
BUN 
Blood urea nitrogen 
CBR 
Clinical Benefit Rate 
CDISC 
Clinical Data Interchange Standards Consortium 
Ceoi 
Concentration at end of infusion 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
CIOMS 
Council of International Organizations of Medical Sciences 
CK 
Creatine kinase 
CL 
Clearance 
Cmax 
Maximum observed concentration 
CPR 
Cardio-pulmonary resuscitation 
CONSORT 
Consolidated Standards of Reporting Trials 
CPK 
Creatine phosphokinase 
CR 
Complete Response 
CRF 
Case Report Form 
CRP 
C-reactive protein 
CSR 
Clinical study report 
CT 
Computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctrough 
Trough plasma concentration 


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CV 
Coefficient of variation 
CTFG 
Clinical Trial Facilitation Group 
CYP 
Cytochrome P 
cys-mcMMAF 
Cysteine maleimidocaproyl monomethyl auristatin F 
CX 
Cycle X 
CX+ 
Cycle X and beyond 
DCO 
Data cut-off 
DILI 
Drug-induced liver injury 
DLT 
Dose limiting toxicity 
DNA 
Deoxyribonucleic acid 
DoR 
Duration of Response 
DRESS 
Drug reaction with eosinophilia and systemic symptoms 
DX 
Day X 
ECG 
Electrocardiogram 
ECHO 
Echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form 
eGFR 
Estimated glomerular filtration rate 
EOI 
End of infusion 
EOT 
End of treatment 
FDA 
Food and Drug Administration 
FISH 
Fluoroscence in situ hybridization 
FLC 
Free light chain 
FSH 
Follicle stimulating hormone 
FTIH 
First Time in Human 
GCP 
Good Clinical Practice 
GFR 
Glomerular filtration rate 
GGT 
Gamma glutamyl transferase 
GLDH 
Glutamate dehydrogenase 
GSK 
GlaxoSmithKline 
HBV 
Hepatitis B 
HBcAb 
Hepatitis B core antibody 
HBsAb 
Hepatitis B surface antibody 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HDT 
High-dose conventional therapy 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human Immunodeficiency Virus 
Hr 
hour 
HRT 
Hormone replacement therapy 
HUS 
Hemolytic uremic syndrome 
IB 
Investigator Brochure 
ICD 
Immunogenic cell death 
ICF 
Informed consent form 
ICH 
International Conference on Harmonization 
IEC 
Institutional Ethics Committee 


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IgA 
ImmunoglobulinA 
IgD 
ImmunoglobulinD 
IgE 
ImmunoglobulinE 
IgG 
ImmunoglobulinG 
IgM 
ImmunoglobulinM 
IHC 
Immunohistochemistry 
IMiD 
Immunomodulatory drugs 
IMWG 
International Myeloma Working Group 
INR 
International normalization ratio 
IP 
Investigational product 
IRB 
Institutional review board 
IRR 
Infusion-related reaction 
IUD 
Intra-uterine device 
IUS 
Intrauterine hormone-releasing system 
IV 
Intravenous(ly) 
LAM 
Lactational amenorrhoea method 
LC 
Light chain  
LDH 
Lactate dehydrogenase 
LLN 
Lower limit of normal (range) 
LVEF 
Left ventricular ejection fraction 
mAb 
Monoclonal antibody 
MCV 
Mean corpuscular volume 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCRN 
Myeloma Canada Research Network 
MDRD 
Modified diet in renal disease 
MHW 
Ministry of Health, Labour and Welfare 
MedRA 
Medical Dictionary for Regulatory Activities 
MM 
Multiple myeloma 
MMAF 
Monomethyl auristatin F 
mPFS 
Median progression-free survival 
MR 
Minimal Response. 
MRI 
Magnetic resonance imaging 
MRP 
Multidrug resistance associated protein 
MSDS 
Material Safety Data Sheet 
NA 
Not applicable 
NCI 
National Cancer Institute 
NE 
Not estimable 
NHL 
Non-Hodgkin lymphoma 
NR 
Not reached 
OATP 
Organic anion transporting polypeptide 
ORR 
Overall Response Rate 
OS 
Overall survival 
PACT 
Post analysis continued treatment 
PC 
Plasma cells 
PCI 
Potential clinical concern 


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PD 
Pharmacodynamic(s) 
PET 
Positron emission tomography 
PFS 
Progression-free survival 
P-gp 
P-glycoprotein 
PK 
Pharmacokinetic(s) 
PML 
Progressive multifocal leukoencephalopathy 
POEMS 
Polyneuropathy, organomegaly, endocrinopathy, myeloma protein, 
and skin changes 
Pom/Dex 
Pomalidomide and dexamethasone 
PR 
Partial response 
PRES 
Posterior reversible encephalopathy syndrome 
PTS 
Platform Technology and Sciences 
QD 
Once daily 
Q3W 
Once every 3 weeks 
Q4W 
Once every 4 weeks 
QID 
Four times a day 
QTc 
Corrected QT interval (ECG) 
QTcF 
Corrected QT interval Fridericia 
Rac 
Accumulation ratio 
RAP 
Reporting and Analysis Plan 
RBC 
Red blood cell 
RNA 
Ribonucleic acid 
RP2D 
Recommended Phase II Dose 
RP3D 
Recommended Phase III Dose 
RRMM 
Relapsed / refractory multiple myeloma 
SAE 
Serious adverse event 
 
 
SC 
Subcutaneous(ly) 
sCR 
Stringent Complete Response 
SCr 
Serum creatinine 
SD 
Stable disease 
SJS 
Stevens-Johnson syndrome 
SoA 
Schedule of activities 
SoC 
Standard of care 
SOI 
Start of infusion 
SPD 
Sum of the products of the maximal perpendicular diameters of 
measured lesions 
SPEP 
Serum Protein Electrophoresis 
SRM 
Study Reference Manual 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
t½ 
Terminal phase half-life 
TEN 
Toxic epidermal necrolysis 
tlast 
Time of last quantifiable concentration 
tmax 
Time of maximum observed concentration 
TNF 
Tumor necrosis factor 
TTP 
Thrombotic thrombocytopenic purpura 
CCI


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ULN 
Upper limit of normal 
UPEP 
Urine protein electrophoresis 
US 
United States 
VGPR 
Very good partial response 
Vss 
Volume of distribution at steady state 
VZIG 
Varicella-Zoster immune globulin 
WBC 
White blood cell 
WOCBP 
Woman of Childbearing Potential  
λz 
Terminal phase elimination rate constant 
 
Trademark Information 
Trademarks of the GlaxoSmithKline 
group of companies 
 
Trademarks not owned by the 
GlaxoSmithKline group of companies 
None 
 
None 
 


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11.11. 
Appendix 11: Protocol Amendment History  
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
Amendment 1: 07-DEC-2018 
Overall Rationale for the Amendment: Action taken for the response to inquiries from 
Pharmaceuticals and Medical Devices Agency (PMDA) (dated 27 NOV 2018) to the 
initial clinical trial notification. 
Section # and 
Name 
Description of Change 
Brief Rationale 
Synopsis 
Changed text of Synopsis to 
reflect changes to the text of the 
protocol. 
See below for all significant changes. 
1.3 Schedule of 
Activities (SoA) 
Added chest X-ray imaging. 
For early detection of interstitial lung 
disease. 
4.1 Overall Design 
Added the dosing interval 
between the first and 
subsequent participants in each 
dose cohort. 
Added the information that the 
dose-escalation will be 
determined considering all 
available information on AEs 
occurred in the dose-limiting 
toxicity (DLT) observation 
period. 
To clearly show how to consider the 
safety information for dose-escalation. 
5.1 Inclusion 
Criteria 4 
Added “at least 2 regimens” to 
the criterion of pretreatment. 
To clearly show that the target 
participants are the patients with no 
options of standard of care. 
5.2 Exclusion 
Criteria 16, 18, and 
21 
Added the following exclusion 
criteria. 
Female who are interrupting 
lactation. 
Those who have positive 
hepatitis B surface antibody 
(HBsAb). 
To make the exclusion criteria clearer 
and to add a new exclusion criterion 
according to the regulatory agency 
advice. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
Those who were previously 
diagnosed with interstitial lung 
disease or who have current 
complication of interstitial lung 
disease. 
6.5.1 Permitted 
Medications(s) 
Added the following information. 
In Japan, it is not approved to 
use growth factor products 
(except for granulocyte-colony 
stimulating factor) for 
neutropenia due to cancer 
chemotherapy and 
erythropoietin products for 
anemia due to cancer 
chemotherapy. 
Some of the treatment participants 
may receive during the study included 
non-approved treatment in Japan. 
6.5.2 Prohibited 
Medications(s) 
Growth factor products: 
prohibited to use for primary 
prophylaxis during DLT 
observation period. 
DLT may be underestimated if growth 
factor products are used during the 
DLT observation period. 
8. Study 
Assessments and 
procedures 
Table 10 
Added HBsAb. 
Based on the revised exclusion 
criterion. 
8.6 
Pharmacodynamics 
Added Table 11: Timing and 
volume of blood collection for 
pharmacokinetic and 
pharmacodynamic analyses. 
To clearly show the timing and volume 
of blood collection for pharmacokinetic 
and pharmacodynamic analyses. 
11.4 Appendix 4: 
Genetics 
Added the following information. 
 
How to store, where to 
store, and how to destroy 
blood samples. 
 
Whether to disclose the 
results of genetic analyses 
to participants, and the 
reason of the action. 
 
How to handle tissue and 
blood samples in case of 
consent withdrawal. 
To clearly show how to handle 
samples, whether to disclose the 
results of analyses, and how to handle 
samples in case of consent withdrawal. 
 


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Amendment 2: 05-APR-2019 
Overall Rationale for the Amendment: This protocol has been amended to address 
feedback from investigators, clarification of study assessment and procedure, and 
administrative change. 
Section # and 
Name 
Description of Change 
Brief Rationale 
1.1. Synopsis 
Changed text of synopsis to 
reflect changes to the text of the 
protocol. 
See below for all significant changes. 
1.3. Schedule of 
Activities (SoA) 
Footnote 1 
Added the time window of Cycle 
(C) 1 Day (D) 2, C1D8, and 
C1D15. 
To clarify the time window. 
1.3. Schedule of 
Activities (SoA) 
Footnote 5 
Clarified that corneal supportive 
care will be done based on 
Grading Scale for Corneal 
Events Associated with 
GSK2857916. 
To make the description consistent 
and aligned throughout the protocol. 
1.3. Schedule of 
Activities (SoA) 
Footnote 6 
Added the time window for 
ocular examination during 
follow-up. 
To clarify the time window for ocular 
examination. 
Changed the timing of follow-up 
visits for participants with 
corneal signs per GSK scale 
after the End of Treatment 
(EOT) visit. 
To align the timing of follow-up visits 
after EOT visit with other GSK2857916 
protocols. 
Added the definition of full 
resolution of ophthalmic 
findings. 
To clarify the definition of full resolution 
of ophthalmic findings. 
1.3. Schedule of 
Activities (SoA) 
Footnote 11 
Added troponin T. 
To assess troponin with troponin I or T. 
1.3. Schedule of 
Activities (SoA) 
Footnotes 21, 22, 
and 23 
Added the procedures for 
sample collection for
 
 
, anti-drug antibodies 
(ADA), and pharmacokinetics 
(PK) assessments when a dose 
is delayed. 
To clarify the timing and number of 
times for sample collection for 
 
ADA, and PK assessments when a 
dose is delayed. 
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Section # and 
Name 
Description of Change 
Brief Rationale 
1.3. Schedule of 
Activities (SoA) 
Genetics Sample 
and Footnote 25 
Revised the timing of collecting 
genetics sample. 
To collect it between the first 
opportunity after a participant has met 
all eligibility requirements and the EOT 
Visit. 
1.3. Schedule of 
Activities (SoA) 
Footnote 27 
Added prednisolone acetate as 
an example of steroid eye drops 
as prophylaxis. 
To clarify the allowed steroid eye drops 
as prophylaxis. 
1.3. Schedule of 
Activities (SoA) 
Adverse Events 
Added adverse events 
assessment at Screening. 
Added Footnote 28 that any 
serious adverse events 
assessed as related to study 
participation or related to a GSK 
product will be recorded from 
the time a participant consent. 
To clarify the timing of collection of 
adverse event information. 
3. Objectives and 
Endpoints 
Removed the requirement for 
pretreatment with the specific 
drug and for drug class from the 
criterion of targeting participants 
for this clinical study. 
To align with current practice. 
5.1. Inclusion 
Criteria #4 
Removed the requirement for 
pretreatment with the specific 
drug and for drug class. 
To align with current practice. 
5.2. Exclusion 
Criteria #18 
Added exemption for 
participants with positive HBsAb 
alone due to hepatitis B 
vaccination. 
To allow participants with positive 
HBsAb alone due to hepatitis B 
vaccination to be enrolled given 
Guidelines for the Management of 
Hepatitis B Virus Infection 
6.5.2. Prohibited 
Medications 
Added strong organic anion 
transporting polypeptide (OATP) 
1B1 and OATP1B3 inhibitors as 
prohibited medications. 
To update information on prohibited 
medications. 
Added prohibition period for 
supportive care. 
To clarify that the requirements for 
prohibited medications. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
6.6.2. Dose 
Reduction for 
Toxicity Table 9 
Incorporated Grading Scale for 
Corneal Events Associated with 
GSK2857916 and amended 
dosing modifications guidelines. 
To further clarify dose modifications 
based on the visual acuity or findings 
on ophthalmic examination. 
6.6.3. Corneal 
Supportive Care 
Guideline 
Clarified that corneal supportive 
care will be done based on 
Grading Scale for Corneal 
Events Associated with 
GSK2857916. 
To make the description consistent 
and aligned throughout the protocol. 
8. Study 
Assessments and 
procedures 
Removed the requirement for 
the order of 12-lead 
electrocardiograms and vital 
signs. 
To allow flexibility for assessments. 
Added the time window of 
C1D2, C1D8, and C1D15. 
To clarify the time window. 
8. Study 
Assessments and 
procedures 
Table 10 
Removed total bicarbonate and 
added troponin T. 
 
Total bicarbonate measurement 
became unnecessary. 
To assess troponin with troponin I or T. 
 
8.1. Efficacy 
Assessments 
Added computed tomography 
and magnetic response imaging 
as methods to assess complete 
response (CR) and stringent 
complete response (sCR). 
To clarify additional methods to assess 
CR and sCR. 
8.2.2. Ocular 
Examinations and 
Procedures 
Revised the examination item at 
baseline ophthalmic examination 
from pupillary examination to 
pupillary light reflex. 
To clarify the examination item. 
11.1.2. Financial 
Disclosure 
Revised information about 
financial disclosure. 
To apply GSK’s standard process of 
financial disclosure. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
11.5. Appendix 5: 
Liver Safety: 
Required Actions 
and Follow-up 
Assessments and 
Study Treatment 
Rechallenge 
Guidelines 
More classified liver chemistry 
stopping criteria and added 
follow up assessments. 
To provide Liver Chemistry Stopping 
Criteria and Required Actions and 
Follow up Assessments according to 
GSK’s standard template. 
11.7. Appendix 7: 
Corneal Event 
Severity Grading 
and Mitigation 
Strategy 
Added prednisolone acetate as 
an example of steroid eye drops 
as prophylaxis. 
To clarify the allowed steroid eye drops 
as prophylaxis. 
11.7. Appendix 7: 
Corneal Event 
Severity Grading 
and Mitigation 
Strategy Table 12 
Added prednisolone acetate as 
an example of steroid eye drops 
as prophylaxis. 
To clarify the allowed steroid eye drops 
as prophylaxis. 
11.7. Appendix 7: 
Corneal Event 
Severity Grading 
and Mitigation 
Strategy Table 13 
Revised Grade 2 and Grade 3 
ophthalmic examination findings 
as follows: 
Grade 2 
 
Moderate keratopathy to 
moderate punctate 
keratopahy. 
Grade 3 
 
Severe keratopathy to 
severe punctate 
keratopahy. 
To clarify the ophthalmic examination 
findings that are assessed as Grade 2 
and Grade 3. 
Added how to perform corneal 
event grading into the footnotes. 
To clarify how to perform corneal event 
grading. 
11.7. Appendix 7: 
Corneal Event 
Severity Grading 
and Mitigation 
Strategy Table 14 
Revised guidance on grading 
based on changes in visual 
acuity to use Landolt ring chart. 
To provide change grading scale for 
visual acuity using Landolt ring chart. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
11.9 Appendix 9: 
International 
Myeloma Working 
Group Uniform 
Response Criteria 
for Multiple 
Myeloma 
Added International Myeloma 
Working Group Uniform 
Response Criteria for Multiple 
Myeloma. 
To clarify the response criteria. 
 
Amendment 3: 01-JUL-2020 
Overall Rationale for the Amendment: This protocol has been amended to add 
combination therapy cohorts of GSK2857916 with bortezomib and dexamethasone 
(Part 2 Arm A) or with pomalidomide and dexamethasone (Part 2 Arm B).  Additional 
changes were incorporated which align with program revisions and/or updates based on 
data from the primary analysis of the Phase II Study 205678 (DREAMM-2) evaluating 
the efficacy and safety of two doses of GSK2857916 monotherapy in relapsed / 
refractory multiple myeloma refractory to proteasome inhibitors, immunomodulatory 
drugs and who failed anti-CD38 antibody treatment. 
Section # and 
Name 
Description of Change 
Brief Rationale 
1.1. Synopsis 
Changed text of synopsis to 
reflect changes to the text of the 
protocol. 
See below for all significant changes. 
1.2. Schema 
4.1. Overall Design 
Figure 2 
Added Part 2 (GSK2857916 
combination therapy). 
To include GSK2857916 combination 
therapy cohorts. 
1.3. Schedule of 
Activities (SoA) 
Table 1 Pregnancy 
test and footnote 
13 
Updated the pregnancy test and 
the follow-up period of 
pregnancy assessment for Part 
1. 
To align with Food and Drug 
Administration (FDA) guidance 
“Oncology Pharmaceuticals 
Reproductive Toxicity and Testing 
recommendations” and considering the 
half-life of GSK2857916. 
1.3. Schedule of 
Activities (SoA) 
Table 1 
Added preservative-free artificial 
tears and cooling eye masks 
(optional) instead of steroid eye 
drops. 
To align with revised prophylactic 
measures for corneal events. 
Added new anticancer therapy 
record during follow up. 
To clarify the collection of new 
anticancer therapy. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
1.3. Schedule of 
Activities (SoA) 
Table 1 Adverse 
events and 
concomitant 
medications 
Added adverse event and 
concomitant medication 
assessments at the follow-up 
visit. 
To clarify adverse event (AE) and 
concomitant medication assessment 
1.3. Schedule of 
Activities (SoA) 
Table 1 footnote 3 
Updated the timing of the end of 
treatment visit. 
To align with program level language. 
1.3. Schedule of 
Activities (SoA) 
Table 1 footnotes 7 
and 21 
Added time window for vital sign 
assessments and
 
) 
blood collection. 
To add clarity of the window. 
1.3. Schedule of 
Activities (SoA) 
Table 1 footnote 27 
Clarified the period to collect 
serious AEs assessed as 
related to study participation or 
related to a GSK product. 
Updated the period to collect 
non-serious and serious AEs. 
Added the requirement of 
concomitant medication record. 
 
1.3. Schedule of 
Activities (SoA) 
Added Table 2: Schedule of 
Activities for Part 2 Arm A 
(GSK2857916 in combination 
with Bortezomib plus 
Dexamethasone). 
Added Table 3: Schedule of 
Activities for Part 2 Arm B 
(GSK2857916 in combination 
with Pomalidomide plus 
Dexamethasone). 
To include assessments and 
procedures for Part 2. 
2. Introduction 
Updated the multiple myeloma 
(MM) information. 
To reflect the latest information of MM. 
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Section # and 
Name 
Description of Change 
Brief Rationale 
2.1. Study 
Rationale 
Updated the results of 
BMA117159 study. 
To reflect the latest information of 
BMA117159 study. 
Updated the information of other 
studies of GSK2857916 
combination therapy. 
To provide the rationale of including 
GSK2857916 combination therapy 
cohorts for this study. 
2.3 Antibody-Drug 
Conjugate 
GSK2857916 
Added the mechanism of action 
of GSK2857916. 
 
2.3.1. Human 
Experience with 
GSK2857916 
Added Section 2.3.1.1 and 
updated the information of 
clinical studies with 
GSK2857916 monotherapy. 
To provide the latest information of 
clinical studies with GSK2857916. 
Added Section 2.3.1.1.1 and 
updated the safety information 
of GSK2857916 monotherapy. 
Added Section 2.3.1.2 to 
describe the information of 
clinical studies with 
GSK2857916 combination 
therapy. 
2.3.1.3. 
Pharmacokinetics 
and 
Pharmacodynamics 
in Human 
Updated the pharmacokinetics 
(PK) and added the 
pharmacodynamics (PD) of 
GSK2857916. 
To reflect the latest PK and PD of 
GSK2857916. 
2.4.1. Risk 
Assessment 
Added the potential overlapping 
toxicities of GSK2857916 when 
combined with bortezomib and 
dexamethasone (Bor/Dex) or 
pomalidomide and 
dexamethasone (Pom/Dex) and 
other risks related to 
GSK2857916, bortezomib, 
pomalidomide, or 
dexamethasone. 
To provide the risks related to study 
treatment. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
2.4.2. Benefit 
Assessment 
Updated the benefit assessment 
for GSK2857916 monotherapy. 
To provide the latest benefit 
assessment for GSK2857916 
monotherapy. 
Added the benefit assessment 
for GSK2857916 combination 
therapy. 
To provide the rationale for the 
potential benefit of including 
GSK2857916 combination therapy 
cohorts. 
2.4.3. Overall 
Benefit: Risk 
Conclusion 
Added the overall benefit and 
risk conclusion for GSK2857916 
combination therapy. 
To provide the overall risk-benefit 
balance of including GSK2857916 
combination therapy cohorts. 
3. Objectives and 
Endpoints Table 4 
Updated the endpoints for the 
objective of evaluating PK 
profile of GSK2857916 and 
cys-mcMMAF after IV single 
and repeat dose administration 
in Japanese participants with 
RRMM. 
To include GSK2857916 combination 
therapy cohorts. 
4.1. Overall Design 
Added the study design and 
planned sample size for Part 2. 
To include GSK2857916 combination 
therapy cohorts. 
Added Table 7: Dose Level for 
Part 2 Arm A and Table 8: Dose 
Levels for Part 2 Arm B. 
To clarify the dose levels used for 
each part and each arm. 
4.1.1. 
Dose-Limiting 
Toxicity 
Added the definitions of dose-
limiting toxicity (DLT) and DLT-
evaluable participants and the 
requirement for replacement of 
participants during the DLT 
observation period for Part 2. 
To include GSK2857916 combination 
therapy cohorts. 
4.2. Scientific 
Rationale for Study 
Design 
Updated the results of 
BMA117159 study. 
To reflect the latest information of 
BMA117159 study. 
Added the rationale of including 
GSK2857916 combination 
therapy cohorts for this study. 
To include GSK2857916 combination 
therapy cohorts. 
4.3. Justification for 
Dose 
Added Section 4.3.2 to provide 
justification for dose for Part 2. 
To include GSK2857916 combination 
therapy cohorts. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
4.4. End of Study 
Definition 
Added the definitions of study 
completion and study 
withdrawal. 
To clarify the definition of completion 
of study treatment and withdrawal of 
study treatment. 
5.1. Inclusion 
Criteria #4 
Revised the requirement for 
prior therapy. 
To expand target population for Part 2. 
5.1. Inclusion 
Criteria #7 
Updated the duration of 
contraception and of refraining 
from donating eggs for female 
participants in Part 1. 
Added the requirement of 
pregnancy test and the duration 
of contraception and of 
refraining from donating eggs 
for female participants for Part 
2. 
To align with FDA guidance “Oncology 
Pharmaceuticals Reproductive Toxicity 
and Testing recommendations” and 
considering the half-life of 
GSK2857916. 
5.1. Inclusion 
Criteria #8 
Updated the duration of 
contraception and of refraining 
from donating sperm for male 
participants. 
Updated the contraceptive 
requirement for male 
participants including those who 
have undergone a successful 
vasectomy to use a male 
condom. 
To align with FDA guidance “Oncology 
Pharmaceuticals Reproductive Toxicity 
and Testing recommendations” and 
considering the half-life of 
GSK2857916. 
5.1. Inclusion 
Criteria #9 
Revised to enroll participants 
with Grade 2 peripheral 
neuropathy only into Part 1 and 
Part 2 Arm B. 
To include GSK2857916 combination 
therapy cohorts. 
5.1. Inclusion 
Criteria #10 
Added Table 10: Criteria for 
Determining Adequate Organ 
System Function for Part 2 
To provide the criteria of adequate 
organ system functions for Part 2. 
5.2. Exclusion 
Criteria 
Added #22 to #24 as Part 2 
Arm A-specific exclusion 
criteria. 
Added #25 to #27 as Part 2 
Arm B-specific exclusion 
criteria. 
To include GSK2857916 combination 
therapy cohorts. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
5.3. Lifestyle 
Considerations 
11.7. Appendix 7: 
Corneal Event 
Severity Grading 
and Mitigation 
Strategy 
Updated the period of 
prohibiting contact lenses. 
Added the possibility of 
restarting contact lens use. 
Allowed bandage contact lenses 
during the study treatment. 
To clarify lifestyle considerations. 
5.3. Lifestyle 
Considerations 
Added restrictions of blood 
donation for Part 2 Arm B 
participants. 
To update lifestyle considerations due 
to combination with Bor/Dex or 
Pom/Dex. 
6. Study Treatment 
Added Table 12: Study 
Treatments Administered for 
Part 2 
To include GSK2857916 combination 
therapy cohorts. 
Added Section 6.2 to describe 
the treatments administered for 
Part 2. 
6.1. GSK2857916 
Treatments 
Administered for 
Part 1 
Added how to calculate the 
actual dose of GSK2857916. 
To simplify the structure of this 
protocol. 
6.5. Study 
Treatment 
Compliance 
Added how to assess study 
treatment compliance for self-
administered oral study 
treatments at home. 
Participants in Part 2 will receive study 
treatments orally at home. 
6.6 Concomitant 
Therapy 
Added the requirement of 
recording concomitant 
medications for serious AEs and 
AEs of special interest (AESIs). 
To clarify the requirement of recording 
concomitant medications. 
6.6.1. Permitted 
Medications 
Added recommendation of 
thromboprophylaxis for 
participants treated with 
pomalidomide, herpes zoster 
prophylaxis, and prophylactic 
treatment for tumor lysis 
syndrome. 
To add recommendation due to 
combination with Bor/Dex or Pom/Dex. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
6.6.2. Prohibited 
Medications 
Added live or live-attenuated 
vaccines as a prohibited therapy 
for Part 2. 
Addition of wording due to language 
associated with dexamethasone. 
Added prohibited medications 
for participants treated with 
pomalidomide or bortezomib. 
To include GSK2857916 combination 
therapy cohorts. 
6.7. Dose 
Modification and 
Delay 
Added Section 6.7.1 to describe 
the detailed guideline of dose 
modification and delay for Part 
1. 
To simplify the structure of this 
protocol. 
Added Section 6.7.2 and 
Section 6.7.3 to provide dose 
modification and delay 
guidelines for Part 2. 
To include GSK2857916 combination 
therapy cohorts. 
6.7.4 Corneal 
Supportive Care 
Guidelines 
Updated the frequency of ocular 
examinations.  
To make the statement suitable for 
Part 2 Arm B. 
7. Discontinuation 
of Study Treatment 
and 
Discontinuation/ 
Withdrawal 
Added Section 7.1.1 to clarify 
the stopping criteria of each 
component of combination study 
treatment in Part 2. 
To include GSK2857916 combination 
therapy cohorts. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
7.1.2. Liver 
Chemistry Stopping 
Criteria 
7.1.2.1. Study 
Treatment Restart 
or Rechallenge 
after Liver Stopping 
Criteria Met 
11.5. Appendix 5 
Liver Safety: 
Required Actions 
and Follow-up 
Assessments and 
Study Treatment 
Rechallenge 
Guidelines 
11.5.1.1. 
Rechallenge 
Following Liver 
Stopping Events 
that are Possibly 
Related to Study 
Treatment 
11.5.1.2. Restart 
Following Transient 
Resolving Liver 
Stopping Events 
Not Related to 
Study Treatment 
Reflected the latest liver 
language template. 
To reflect the liver language template 
update. 
8. Study 
Assessments and 
Procedures 
Updated visit window of 
pregnancy test, bone marrow 
archival tissue, and each study 
visit’s assessments. 
To include GSK2857916 combination 
therapy cohorts and to add clarity. 
8.1. Efficacy 
Assessments 
Updated the frequency of serum 
and urine-based assessments 
(M-protein, free light chain, 
immunofixation). 
To make the statement suitable for 
Part 2 Arm B. 


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Section # and 
Name 
Description of Change 
Brief Rationale 
8.2.7. Clinical 
Safety Laboratory 
Assessments 
Updated the period to perform 
repeated laboratory tests for 
parameters with values 
considered clinically significantly 
abnormal. 
 
8.3.1. Time Period 
and Frequency for 
Collecting AE and 
SAE Information 
Updated the period to collect 
non-serious and serious AEs. 
 
8.3.5. Adverse 
Events of Special 
Interest 
Updated how to assess severity 
of corneal events and other 
AESIs 
Corneal events will be assessed using 
National Cancer Institute-Common 
Toxicity Criteria for Adverse Events 
and GSK scale. 
8.3.6. Pregnancy 
Updated the pregnancy test and 
the follow-up period of 
pregnancy assessment for Part 
1. 
Added the pregnancy test and 
the follow-up period of 
pregnancy assessment for Part 
2. 
To align with FDA guidance “Oncology 
Pharmaceuticals Reproductive Toxicity 
and Testing recommendations” and 
considering the half-life of 
GSK2857916. 
8.3.6. Pregnancy  
11.3.3. Collection 
of Pregnancy 
Information 
Added the period to collect 
pregnancy information from 
female participant and male 
participant’s female partner. 
To clarify the period to collet 
pregnancy information in Part 2 and to 
align with FDA guidance “Oncology 
Pharmaceuticals Reproductive Toxicity 
and Testing recommendations” 
considering the half-life of 
GSK2857916, 
8.4. Treatment of 
Overdose 
A blood sample for
 will 
also be obtained in the event of 
an overdose. 
PK measurement needs 
 
concentration. 
Added the information of 
overdose treatment for 
pomalidomide, bortezomib, and 
dexamethasone. 
To include GSK2857916 combination 
therapy cohorts. 
CCI
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Section # and 
Name 
Description of Change 
Brief Rationale 
8.6. 
Pharmacodynamics 
Revised timing of blood 
collection for PD analyses. 
To add clarity of the window. 
Added Table 32: Timing and 
Volume of Blood Collection for 
GSK2857916 Pharmacokinetic 
and Pharmacodynamic 
 Analyses (Part 2 Arm 
A). 
To clarify the sampling time and blood 
volume for PK and PD analyses of 
GSK2857916 in Part 2. 
Added Table 33: Timing and 
Volume of Blood Collection for 
GSK2857916 Pharmacokinetic 
and Pharmacodynamic 
) Analyses (Part 2 Arm 
B). 
8.9. 
Immunogenicity 
Assessments 
Added the detailed description 
of immunogenicity assessments 
and analyses. 
To perform immunogenicity 
assessments in GSK2857916 
combination therapy cohorts. 
10.1. Statistical 
Hypotheses 
Clarified that statistical analyses 
will be performed separately for 
each part and each arm. 
To include GSK2857916 combination 
therapy cohorts. 
10.2. Sample Size 
Determination 
Added the planned sample size 
for Part 2. 
To include GSK2857916 combination 
therapy cohorts. 
10.3. Populations 
for Analyses 
Updated the definitions of all 
treated population and DLT 
evaluable population. 
Clarified that each analysis 
population will be created 
separately for each part and 
each arm. 
To include GSK2857916 combination 
therapy cohorts. 
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Section # and 
Name 
Description of Change 
Brief Rationale 
10.4. Statistical 
Analyses 
10.4.1 Safety 
Analyses 
10.4.1.1. Extent of 
Exposure 
10.4.2. Efficacy 
Analyses 
10.4.3. 
Immunogenicity 
Analyses 
Clarified that each statistical 
analysis will be performed 
separately for each part and 
each arm. 
To include GSK2857916 combination 
therapy cohorts. 
10.4.4.1 
Concentration-Time 
Data 
10.4.4.2 Derived 
Pharmacokinetic 
Parameters 
Updated the planned analyses 
of PK parameters of 
GSK2857916. 
To align with the current analysis plan 
and to include GSK2857916 
combination therapy cohorts. 
10.5. Interim 
Analyses 
Added Section 10.5.1 and 
clarified the data cut-off for 
Part 1. 
To perform interim analysis for Part 1 
of this study. 
Added Section 10.5.2 to add 
interim analyses for Part 2. 
To perform interim analyses for Part 2 
of this study. 
CCI


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Section # and 
Name 
Description of Change 
Brief Rationale 
11.7. Appendix 7: 
Corneal Event 
Severity Grading 
and Mitigation 
Strategy 
Made steroid eye drops as 
prophylaxis for corneal events 
optional. 
Added the option to use 
corticosteroid eye drops as 
prophylaxis for corneal events 
optional. 
Based on available data from overseas 
study, steroid eye drops were removed 
from mandatory prophylactic measures 
for corneal events. 
Updated how to assess severity 
of corneal events. 
Corneal events will be assessed using 
National Cancer Institute-Common 
Toxicity Criteria for Adverse Events 
and GSK scale. 
11.7. Appendix 7: 
Corneal Event 
Severity Grading 
and Mitigation 
Strategy Table 34 
Deleted steroid eye drops as 
prophylaxis for corneal events 
associated with GSK2857916. 
Based on available data from overseas 
study, steroid eye drops were removed 
from mandatory prophylactic measures 
for corneal events. 
11.1.11. Study 
Period 
Deleted the study period. 
To move the study period to Exhibit 3. 
 
Amendment 4: 15-JAN-2021 
Overall Rationale for the Amendment: This protocol has been amended to address 
feedback from investigators, to clarify study assessment and procedures, and to reflect 
administrative change. Additional changes were incorporated to align with program-wide 
revisions and/or updates. 
Section # and Name 
Description of Change 
Brief Rationale 
1.1. Synopsis 
Changed text of synopsis 
to reflect changes to the 
text of the protocol. 
See below for all significant 
changes. 
1.3. Schedule of Activities 
(SoA) 
Added Table 4 for 
additional procedures for 
participants with a history 
of Hepatitis B. 
In line with program wide 
update. 
1.3. Schedule of Activities 
(SoA) for Part 2 Arm A 
Updated timepoint for 12-
lead ECG. 
Updated footnote 27. 
To clarify the timepoint. 
Administrative changes were 
made as described. 


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Section # and Name 
Description of Change 
Brief Rationale 
5.1. Inclusion Criteria #4 
Revised the requirement 
for most recent therapy for 
Part 2. 
To ensure consistency in target 
population with DREAMM-7 / 
207503 study and DREAMM-8 / 
207499 study. 
5.2. Exclusion Criteria #18 
Updated exclusion criteria 
for Hep B+ participants. 
In line with program wide 
update. 
6.2.1. GSK2857916 with 
Bortezomib/Dexamethasone 
(Arm A) 21-day Cycle 
Clarified language 
regarding dosing schedule 
for GSK2857916. 
To clarify dosing schedule for 
GSK2857916. 
6.2.2. GSK2857916 with 
Pomalidomide/Dexamethasone 
(Arm B) 28-day Cycle 
Clarified language 
regarding dosing schedule 
for GSK2857916. 
To clarify dosing schedule for 
GSK2857916. 
6.7.2. Dose Modification and 
Delay for Part 2 Arm A 
Updated dose modification 
guidelines for adverse 
events associated with 
GSK2857916 for Part 2 
Arm A. 
Updated dose modification 
guideline for GSK2857916 
treatment-related corneal 
events for Part 2. 
Updated dose delay 
scenario for GSK2857916. 
To align with program level 
language. 
 
 
In line with program wide 
update.  
 
 
To clarify dosing schedule for 
GSK2857916. 
6.7.3. Dose Modification and 
Delay for Part 2 Arm B 
Updated dose delay 
scenario for GSK2857916. 
To clarify dosing schedule for 
GSK2857916. 
6.7.4. Management of 
Hepatitis B+ participants 
Added section to clarify 
management of Hepatitis 
B+ participants 
In line with program wide 
update. 
 
Amendment 5: 12-NOV-2021 
Overall Rationale for the Amendment: This protocol has been amended to clarify the 
timing and purpose of analyses. 


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Section # and Name 
Description of Change 
Brief Rationale 
1.3. Schedule of Activities 
(SoA) 
Table 3 
Added examination points 
for IgG, IgM and IgA at C2 
D1 and C3 to CX D1 
Corrected 
2.3.1. Human Experience with 
GSK2857916 
2.3.1.3. Pharmacokinetics and 
Pharmacodynamics in Human 
Background information 
has been amended to be 
consistent with clarifications 
and updates made in the 
most current version of the 
Investigator Brochure 
(v9.0). 
To align language with the most 
current version of the 
Investigator Brochure (v9.0). 
2.4.1 Risk Assessment 
Risks from Study Procedures 
Updated the procedure of 
incidental findings during 
image acquisition. 
To align with program level 
language. 
8.3. Adverse Events and 
Serious Adverse Events 
8.3.1. Time Period and 
Frequency for Collecting AE 
and SAE Information 
Deleted the description 
related to post-marketing 
study. 
This study is not applicable. 
8.3. Adverse Events and 
Serious Adverse Events 
8.3.3. Follow-up of AEs and 
SAEs 
Deleted the description 
related to post-marketing 
study. 
This study is not applicable. 
8.3. Adverse Events and 
Serious Adverse Events 
8.3.4. Regulatory Reporting 
Requirements for SAEs 
Deleted the description 
related to post-marketing 
study. 
This study is not applicable. 
10. Statistical Considerations 
Added the description for 
primary analysis in Part 1 
and for potential interim 
analysis and primary 
analysis in Part 2. 
To clarify the purpose and timing 
for analyses. 
10.5. Interim Analyses 
10.5.1 Part 1 
10.5.2. Part 2 
Part1: Deleted the 
description on data cut-off.  
Part2: Added potential 
interim analysis. 
To clarify the purpose and timing 
for analyses. 


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Section # and Name 
Description of Change 
Brief Rationale 
11.2. Appendix 2: Adverse 
Events: Definitions and 
Procedures for Recording, 
Evaluating, Follow-up, and 
Reporting 
11.2.4. Recording and Follow-
Up of AE and SAE 
Deleted the description 
related to post-marketing 
study. 
This study is not applicable. 
11.2. Appendix 2: Adverse 
Events: Definitions and 
Procedures for Recording, 
Evaluating, Follow-up, and 
Reporting 
11.2.5. Reporting of SAE to 
GSK 
SAE Reporting to GSK via 
Electronic Data Collection 
Tool 
SAE Reporting to GSK via 
Paper CRF 
Deleted the description 
related to post-marketing 
study. 
This study is not applicable. 
 


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12. 
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Belnoue E, Pihlgren M, McGaha TL, et al. APRIL is critical for plasmablast survival in 
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Cowan AJ, Allen C, Barac A, et al. Global Burden of Multiple Myeloma: A Systematic 
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during human B cell differentiation. J Immunol. 2007 Dec 1;179(11):7276-86. 
GSK Document Number 2013N175128_09. 2021 GSK2857916 Investigator's Brochure. 
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Hunt, CM. Mitochondrial and immunoallergic injury increase risk of positive drug 
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James LP, Letzig L, Simpson PM, Capparelli E, Roberts DW, Hinson JA, Davern TJ, Lee 
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Jiang C, Loo WM, Greenley EJ, et al. B cell maturation antigen deficiency exacerbates 
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Janssen-Cilag International NV. Darzalex (daratumumab) summary of Product 
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Kumar SK, Lee JH, Lahuerta JJ, et al. Risk of progression and survival in multiple 
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Improved survival in multiple myeloma and the impact of novel therapies. Blood. 
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Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group 
consensus criteria for response and minimal residual disease assessment in multiple 
myeloma. The Lancet Oncology. 2016;17: e328-e346. 
Langat DL, Wheaton DA, Platt JS, Sifers T, Hunt JS. Signaling pathways for B cell-
activating factor (BAFF) and a proliferation-inducing ligand (APRIL) in human placenta. 
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Laurent SA, Hoffmann FS, Kuhn PH, et al. gamma-Secretase directly sheds the survival 
receptor BCMA from plasma cells. Nat Commun. 2015; 6:7333. 
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Hepatitis Delta Virus RNA in Serum by Consensus Real-Time PCR Indicates Different 
Patterns of Virological Response to Interferon Therapy in Chronically Infected Patients. 
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Li Y, Xu Y, Liu L, et al. Population pharmacokinetics of pomalidomide. J Clin 
Pharmacol. 2015;55(5):563-572. 
Lonial S, Lee HC, Badros A, et al. Belantamab mafodotin for relapsed or refractory 
multiple myeloma (DREAMM-2): a two-arm, randomized, open-label, phase 2 study. 
Lancet Oncol. 2020:21:207-21. 
Montes De Oca R, Bhattacharya S, Vitali N, et al. The anti-BCMA antibody-drug 
conjugate GSK2857916 drives immunogenic cell death and immune-mediated anti-tumor 
responses, and in combination with an OX40 agonist potentiates in vivo activity. 
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Nijhof IS, van de Donk NWCJ, Zweegman S, et al. Current and New Therapeutic 
Strategies for Relapsed and Refractory Multiple Myeloma: An Update. Drugs. 2018 
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Novak AJ, Darce JR, Arendt BK, et al. Expression of BCMA, TACI, and BAFF-R in 
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Ozaki S, Handa H, Murkami H, et al. Trends of survival in patients with multiple 
myeloma in Japan: a multicenter retrospective collaborative study of the Japanese Society 
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Papay JI, Clines D, Rafi R, et al. Drug-induced liver injury following positive drug 
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Tai YT, Anderson KC. Targeting B-cell maturation antigen in multiple myeloma. 
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Tai YT, Li XF, Breitkreutz I, et al. Role of B-cell-activating factor in adhesion and 
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Res. 2006;66(13):6675-82. 
Tai YT, Mayes PA, Acharya C, et al. Novel anti-B-cell maturation antigen antibody-drug 
conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood. 
2014;123:3128-38. 
Trudel S, Lendvai N, Popat R, et al. Targeting B-cell maturation antigen with 
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Signature Page for RPS-CLIN-050928 v1.0
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PPD

SAP_001.pdf: 
Statistical Analysis Plan- Part 1 & Part 2 
Study ID:  207504
Official Title of Study: A Phase I Open-Label, Dose Escalation Study to 
Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, 
Immunogenicity and Clinical Activity of the Antibody Drug Conjugate 
GSK2857916 in Japanese Participants With Relapsed/Refractory Multiple 
Myeloma
NCT ID : NCT03828292
Date of Document of Part 1: 17 December 2021
Date of Document of Part 2: 28 April 2023


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
 
207504 
1 
Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
Title 
: Reporting and Analysis Plan for A Phase I Open-Label, 
Dose Escalation Study to Investigate the Safety, 
Tolerability, Pharmacokinetics, Pharmacodynamics, 
Immunogenicity and Clinical Activity of the Antibody Drug 
Conjugate GSK2857916 in Japanese Participants with 
Relapsed/Refractory Multiple Myeloma (Part 1) 
Compound Number  : GSK2857916 
Effective Date 
: Refer to Document Date 
Description: 
•
The purpose of this RAP is to describe the planned analyses and output to be
included in the Clinical Study Report (Part 1) for Protocol 207504.
•
This RAP is intended to describe the safety, pharmacokinetic, and efficacy
analyses required for the study (Part 1).
•
This RAP will be provided to the study team members to convey the content of the
Statistical Analysis Complete (SAC) deliverable.
RAP Author(s): 
Author 
Date 
 
14-DEC-2021
Senior Biostatistician, Biostatistics FSP, 
PAREXEL employee on behalf of 
GlaxoSmithKline K.K. 
Copyright 2021 the GlaxoSmithKline group of companies. All rights reserved. 
Unauthorised copying or use of this information is prohibited.
PPD


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
 
207504 
2 
Parexel Review Confirmations (Method: E-mail) 
Reviewer 
Date 
 
15-DEC-2021
Senior Data Management Lead, 
Parexel International 
 
15-DEC-2021
Principal Statistical Programmer, 
Statistical Programming FSP,  
Parexel International 
 
15-DEC-2021
Medical Writer, 
Medical Writing Services, 
Parexel International 
PPD
PPD
PPD


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
 
207504 
3 
GSK Review Confirmations (Method: E-mail) 
Reviewer 
Date 
 
15-DEC-2021
Principal Statistician, Biostatistics, Japan 
Medical and Development,  
GlaxoSmithKline K.K. 
 
16-DEC-2021
Study Accountable Person, Clinical 
Development (Oncology), Oncology Medical 
and Development, Japan Medical and 
Development,  
GlaxoSmithKline K.K. 
 
15-DEC-2021
Programmer, Clinical Programming, 
Biostatistics, Japan Medical and Development, 
GlaxoSmithKline K.K. 
 
15-DEC-2021
Manager, Clinical Pharmacology Asian Hub 
RD Clinical Pharmacology Modeling & 
Simulation, 
GlaxoSmithKline K.K. 
GSK Clinical Statistics and Clinical Programming Line Approvals 
(Method: E-mail) 
Approver 
Date 
 
17-DEC-2021
Department Manager, Clinical Programming, 
Biostatistics, Japan Medical and Development 
GlaxoSmithKline K.K. 
 
17-DEC-2021
 Biostatistics, Japan Medical and 
Development, 
GlaxoSmithKline K.K. 
PPD
PPD
PPD
PPD
PPD
PPD
PPD


 
CONFIDENTIAL 
 
 
 
 
207504 
4 
 
TABLE OF CONTENTS 
PAGE 
1. 
INTRODUCTION ...................................................................................................... 7 
1.1. 
RAP Amendments ........................................................................................ 8 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION .................................................. 8 
2.1. 
Study Objective(s) and Endpoint(s)............................................................... 8 
2.2. 
Study Design .............................................................................................. 10 
2.3. 
Statistical Hypotheses / Statistical Analyses ............................................... 11 
3. 
PLANNED ANALYSES .......................................................................................... 12 
3.1. 
Interim Analyses ......................................................................................... 12 
3.1.1. 
Dose Escalation Reviews ............................................................ 12 
3.1.1.1. 
Displays to Be Created for Dose Escalation 
Review ....................................................................... 13 
3.2. 
Primary Analyses ........................................................................................ 13 
4. 
ANALYSIS POPULATIONS ................................................................................... 15 
4.1. 
Protocol Deviations ..................................................................................... 15 
5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 17 
5.1. 
Study Treatment & Sub-group Display Descriptors ..................................... 17 
5.2. 
Baseline Definitions .................................................................................... 17 
5.2.1. 
Change from baseline .................................................................. 17 
5.3. 
Multicenter Studies ..................................................................................... 18 
5.4. 
Examination of Covariates, Other Strata and Subgroups ............................ 18 
5.4.1. 
Covariates and Other Strata ........................................................ 18 
5.4.2. 
Examination of Subgroups ........................................................... 18 
5.5. 
Multiple Comparisons and Multiplicity ......................................................... 18 
5.6. 
Other Considerations for Data Analyses and Data Handling 
Conventions ................................................................................................ 18 
6. 
STUDY POPULATION ANALYSES ....................................................................... 19 
6.1. 
Overview of Planned Study Population Analyses ........................................ 19 
6.2. 
Disposition of Subjects ................................................................................ 19 
6.3. 
Demographic and Baseline Characteristics ................................................. 19 
6.4. 
Extent of Exposure ..................................................................................... 20 
6.5. 
Concomitant Medications ............................................................................ 21 
7. 
EFFICACY ANALYSES .......................................................................................... 23 
7.1. 
Primary Efficacy Analyses .......................................................................... 23 
7.2. 
Secondary Efficacy Analyses ...................................................................... 23 
7.2.1. 
Endpoint / Variables ..................................................................... 23 
7.2.1.1. 
Unconfirmed and Confirmed Responses .................... 23 
7.2.1.2. 
Best Overall Response (BOR) .................................... 25 
7.2.1.3. 
Overall Response Rate (ORR) ................................... 25 
7.2.1.4. 
Clinical Benefit Rate (CBR) ........................................ 25 
7.2.2. 
Summary Measure for ORR and CBR ......................................... 25 
7.2.3. 
Population of Interest ................................................................... 25 


 
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7.2.4. 
Statistical Analyses / Methods ..................................................... 25 
8. 
SAFETY ANALYSES ............................................................................................. 26 
8.1. 
Adverse Events Analyses ........................................................................... 26 
8.2. 
Adverse Events of Special Interest Analyses .............................................. 27 
8.3. 
Deaths and Serious Adverse Events ........................................................... 28 
8.4. 
Adverse Events Leading to Discontinuation and Dose Modification 
of Study Treatment ..................................................................................... 29 
8.5. 
Clinical Laboratory Analyses ....................................................................... 29 
8.5.1. 
Analyses of Liver Function Tests (LFT) ........................................ 32 
8.5.2. 
Analyses of Disease Evaluation ................................................... 33 
8.5.3. 
Analyses of eGFR ........................................................................ 33 
8.6. 
Other Safety Analyses ................................................................................ 33 
8.6.1. 
Performance Status ..................................................................... 33 
8.6.2. 
ECG ............................................................................................. 33 
8.6.3. 
LVEF ........................................................................................... 34 
8.6.4. 
Ocular Exams .............................................................................. 34 
8.6.5. 
Vital Signs .................................................................................... 36 
8.6.6. 
Anti-Drug Antibody ....................................................................... 37 
8.6.7. 
Pregnancies ................................................................................. 37 
9. 
PHARMACOKINETIC ANALYSES ......................................................................... 38 
9.1. 
Endpoint / Variables .................................................................................... 38 
9.1.1. 
Drug Concentration Measures ..................................................... 38 
9.1.2. 
Derived Pharmacokinetic Parameters .......................................... 38 
9.2. 
Population of Interest .................................................................................. 39 
9.3. 
Statistical Analyses / Methods .................................................................... 39 
9.3.1. 
Assessment of Accumulation Ratio .............................................. 39 
12. PHARMACOKINETIC / PHARMACODYNAMIC ANALYSES ................................. 42 
13. REFERENCES ....................................................................................................... 43 
14. APPENDICES ........................................................................................................ 44 
14.1. 
Appendix 1: Protocol Deviation Management and Definitions for Per 
Protocol Population ..................................................................................... 44 
14.1.1. 
Exclusions from Per Protocol Population ..................................... 44 
14.2. 
Appendix 2: Schedule of Activities .............................................................. 45 
14.3. 
Appendix 3: Assessment Windows ............................................................. 46 
14.3.1. 
Definitions of Assessment Windows for Analyses ........................ 46 
14.4. 
Appendix 4: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................ 47 
14.4.1. 
Study Phases .............................................................................. 47 
14.4.1.1. Study Phases for Concomitant Medication and 
Blood and Blood Supportive Care Product ................. 47 
14.4.2. 
Treatment Emergent Flag for Adverse Events ............................. 49 
14.5. 
Appendix 5: Data Display Standards & Handling Conventions .................... 50 
14.5.1. 
Reporting Process ....................................................................... 50 
14.5.2. 
Reporting Standards .................................................................... 50 
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14.5.3. 
Reporting Standards for Pharmacokinetic .................................... 51 
14.5.4. 
Reporting Standards for Pharmacodynamic ................................. 52 
14.6. 
Appendix 6: Derived and Transformed Data ............................................... 53 
14.6.1. 
General ........................................................................................ 53 
14.6.2. 
Study Population .......................................................................... 53 
14.6.3. 
Safety .......................................................................................... 53 
14.7. 
Appendix 7: Reporting Standards for Missing Data ..................................... 54 
14.7.1. 
Premature Withdrawals ................................................................ 54 
14.7.2. 
Handling of Missing Data ............................................................. 54 
14.7.2.1. Handling of Missing and Partial Dates ........................ 54 
14.8. 
Appendix 8: Values of Potential Clinical Importance ................................... 56 
14.8.1. 
Laboratory Values ........................................................................ 56 
14.8.2. 
ECG ............................................................................................. 56 
14.8.3. 
Vital Signs .................................................................................... 56 
14.9. 
Appendix 9: Abbreviations & Trademarks ................................................... 57 
14.9.1. 
Abbreviations ............................................................................... 57 
14.9.2. 
Trademarks ................................................................................. 57 
14.10. Appendix 10: List of Data Displays.............................................................. 58 
14.10.1. Data Display Numbering .............................................................. 58 
14.10.2. Mock Example Shell Referencing ................................................ 58 
14.10.3. Deliverables ................................................................................. 58 
14.10.4. Study Population Tables .............................................................. 59 
14.10.5. Study Population Figures ............................................................. 65 
14.10.6. Efficacy Tables ............................................................................ 65 
14.10.7. Safety Tables ............................................................................... 66 
14.10.8. Safety Figures ............................................................................. 88 
14.10.14. ICH Listings ............................................................................... 101 
14.10.15. Non-ICH Listings ........................................................................ 106 
14.11. Appendix 11: Example Mock Shells for Data Displays .............................. 108 
14.12. Appendix 12: International Myeloma Working Group Uniform 
Response Criteria for Multiple Myeloma ................................................... 109 
 
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1. 
INTRODUCTION 
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Study Report for Protocol: 2018N369488_05 (Dated: 12-NOV-
2021). This RAP focuses on the analysis plan for monotherapy (Part 1), and the RAP 
focused on the analysis plan for combination therapy (Part 2) will be prepared separately. 
Revision Chronology: 
2018N369488_00 
25-JUL-2018 
Original 
2018N369488_01 
07-DEC-2018 
Amendment No. 1. Action taken for the response to inquiries 
from Pharmaceuticals and Medical Devices Agency (PMDA) 
(dated 27 NOV 2018) to the initial clinical trial notification. 
Added chest X-ray imaging. Added the dosing interval 
between the first and subsequent participants in each dose 
cohort and information that the dose-escalation will be 
determined considering all available information on AEs 
occurring in the DLT observation period. Clarified inclusion 
and exclusion criteria. Clarified use of growth factors as 
prohibited medication. Added timing and volume of blood 
collection for pharmacodynamic and pharmacokinetic 
analyses. 
2018N369488_02 
05-APR-2019 
Amendment No. 2. Amendment to address feedback from 
investigators, clarification of study assessments and 
procedures, and administrative changes. Revised Schedule 
of Activities. Revised inclusion and exclusion criteria. 
Incorporated GSK Scale for Corneal Events Associated with 
GSK2857916, instructions for grading, and dose 
modification guidelines. Added IMWG criteria. 
2018N369488_03 
01-JUL-2020 
Amendment No. 3. Amendment to add combination therapy 
cohorts of GSK2857916 with bortezomib and 
dexamethasone (Part 2 Arm A) or with pomalidomide and 
dexamethasone (Part 2 Arm B). Additional changes were 
incorporated which align with program revisions and/or 
updates based on data from the primary analysis of the 
Phase II study 205678 (DREAMM-2). Revised Schedule of 
Activities. Updated PK and PD of GSK2857916. 
Modifications corresponding to adding the combination 
cohorts of Part 2. Added interim analysis for Part 1 and Part 
2. 
2018N369488_04 
15-JAN-2021 
Amendment No. 4. Amendment to address feedback from 
investigators, to clarify study assessments and procedures, 
and to reflect administrative changes. Revised Schedule of 
Activities and Inclusion/Exclusion criteria. Clarified dosing 
and dose modifications for Part 2 cohorts. 
2018N369488_05 
12-NOV-2021 
Amendment No. 5. Amendment to clarify the timing and 
purpose of analyses. 


 
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1.1. 
RAP Amendments 
Revision chronology:  
RAP Section 
Amendment Details 
238106 RAP 20210318 Part 1 1.0 
238106 RAP 20211214 Part 1 1.0 Amendment 
RAP Authors 
• 
To update the RAP Author 
GSK Review 
Confirmations 
• 
To update the department name 
Section 1. 
• 
To update Revision Chronology for Protocol 
Section 1.1. 
• 
To add Revision chronology for RAP Amendments 
Section 2.2. 
• 
To clarify interim analysis 
Section 3.1. 
• 
To clarify interim analysis 
Section 3.2. 
• 
To clarify primary analysis and final analysis 
Section 6.2. 
• 
To remove the completed study treatment from the summary of study 
treatment status 
Section 6.5. 
• 
To add the derivation for the duration of exposure that was on 
prophylactic steroid eye drop use 
Section 7.2.2. 
• 
To remove the summary of unconfirmed ORR and CBR 
Section 8.2. 
• 
To add the description of additional analysis for corneal event 
Section 8.5. 
• 
To remove the supporting listing with subject level details for urinalysis 
Section 14.7.2.1. 
• 
To change the name of the element (from Medical History to Disease 
Characteristics) appropriately 
Section 14.9.1. 
• 
To add one abbreviation 
Section 14.10. 
• 
To change the title description appropriately (e.g., the removal of 
“Intact” from “Intact ADC” in the displays titles, typo correction) 
Section 14.10.1. 
• 
To change the data display numbering 
Section 14.10.7. 
• 
To add tables for corneal events 
• 
To amend IDSL example numbers 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
2.1. 
Study Objective(s) and Endpoint(s) 
Objectives 
Endpoints 
Primary Objectives 
Primary Endpoints 
• 
To evaluate safety, tolerability of 
GSK2857916 in Japanese participants 
RRMM. 
• 
Number of participants with DLTs 
• 
Adverse events (AEs) and changes in clinical signs and 
laboratory parameters. 
Secondary Objectives 
Secondary Endpoints 
• 
To evaluate pharmacokinetic (PK) profile 
of GSK2857916 and cysteine 
maleimidocaproyl monomethyl auristatin F 
• 
GSK2857916 and cys-mcMMAF PK parameters following IV 
single and repeat dose administration as data permit (e.g., 


 
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Objectives 
Endpoints 
(cys-mcMMAF) after IV single and repeat 
dose administration in Japanese 
participants with RRMM. 
AUCs, Cmax, tmax, CL, Vss, t½ [single dose], Ceoi, Ctrough, 
and Rac (Ceoi and Ctrough) [repeat dose]). 
• 
To assess anti-drug antibody (ADA) 
formation after IV single and repeat dose 
administration of GSK2857916. 
• 
ADA incidence and titers after IV single and repeat dosing of 
GSK2857916. 
• 
To investigate the initial anti-tumor activity 
of GSK2857916 in Japanese participants 
with RRMM. 
• 
Clinical activity measured as Overall Response Rate (ORR) 
and Clinical Benefit Rate (CBR) which are defined as follows: 
o 
ORR: the percentage of participants achieving 
confirmed partial response or better (≥PR) 
o 
CBR: the percentage of participants with minimal 
response (MR) or better 
CCI


 
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2.2. 
Study Design 
Overview of Study Design and Key Features 
 
Design 
Features 
• 
This is a Phase 1, open label, dose escalation study to investigate safety, 
tolerability, pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and 
clinical activity of GSK2857916 when given as monotherapy on a once every 21 
days schedule (Part 1), or given in combination with Bor/Dex on a once every 21 
days schedule (Part 2 Arm A) or with Pom/Dex on a once every 28 days schedule 
(Part 2 Arm B). The study will consist of 2 parts. Part 1 is a dose escalation phase 
to evaluate the safety and tolerability of up to 2 dose levels of GSK2857916 
monotherapy. Part 2 of the study will evaluate the safety and tolerability of 1 dose 
level of GSK2857916 in combination with 2 SoC regimens: Part 2 Arm A – 
GSK2857916 with Bor/Dex, and Part 2 Arm B – GSK2857916 with Pom/Dex.  
• 
The dose escalation model is based on 3 + 3 design. The maximum number of 
participants will be up to 12. The GSK2857916 will be IV administered over 30 min 
infusion once every 3 weeks (21 days = 1 cycle) or every 4 weeks (28 days = 1 
cycle). The initial anti tumor activity of GSK2857916 based on response 
assessment criteria as defined by International Myeloma Working Group (IMWG) 
2016 will also be assessed during the study [Kumar, 2016]. 
Dosing 
• 
In Part 1, GSK2857916 is to be IV administered, via an infusion pump on Day 1 of 
each cycle over 30 minutes. Premedication is not required prior to infusion unless 
deemed medically necessary by the investigator, in which case it should be 
administered according to institutional recommendations. 
• 
In Part 2, GSK2857916 is to be IV administered via an infusion pump. Arm A will 
receive 2.5 mg/kg on Day 1 of each cycle, once every 3 weeks. In addition, Arm A 
will receive 1.3 mg/m2 Bortezomib via subcutaneous injection on Day 1, Day 4, Day 
8, Day 11 Q3W for 8 cycles and 20 mg Dexamethasone orally on Day 1, Day 2, 
Day 4, Day 5, Day 8, Day 9, Day 11, and Day 12, Q3W for 8 cycles. Arm B will 
receive 2.5 mg/kg on Day 1 of Cycle 1 and 1.9 mg/kg on Cycle 2 Day 1 and 
beyond, once every 4 weeks. In addition, Arm B will receive 4 mg orally daily on 
Days 1-21, Q4W and 40 mg Dexamethasone orally per day on Day 1, Day 8, Day 
15, and Day 22 Q4W. 
Time & 
Events 
• 
Refer to Protocol Section 1.3, Tables 1-3 for the schedule of activities relating to 
Part 1 and Part 2.  


 
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Overview of Study Design and Key Features 
Treatment 
Assignment 
• 
This is open-label study and consists of two parts (Part 1, Part 2). There are two 
cohorts (2.5 mg/kg and 3.4 mg/kg) in Part 1 and one cohort for each arm in Part 2 
(2.5 mg/kg with Bor/Dex for Arm A, 2.5 mg/kg at C1D1 and 1.9 mg/kg at C2D1 with 
Pom/Dex for Arm B). 
Interim 
Analysis 
• 
In Part 1, available safety data will be reviewed after the completion of DLT 
evaluation period to determine if a dose-escalation is appropriate. Additionally, PK 
data will be reviewed after the completion of DLT evaluation period to assess PK 
similarity between Japanese and overseas populations. 
• 
In Part 2, available safety data will be reviewed after the completion of DLT 
evaluation period within each arm to determine if the combination dose regimen is 
tolerable. An interim analysis may be conducted when the last participant within any 
arm in Part 2 has completed at least one cycle of the combination treatment to 
evaluate safety, efficacy and PK profiles. 
 
2.3. 
Statistical Hypotheses / Statistical Analyses 
No specific statistical hypotheses are being tested in this study. 


 
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3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
In Part 1, available safety data will be reviewed after the completion of the DLT 
evaluation period to determine if a dose-escalation is appropriate. Additionally, PK data 
will be reviewed after the completion of the DLT evaluation period to assess PK 
similarity between Japanese and overseas populations.  
In Part 2, available safety data will be reviewed after the completion of DLT evaluation 
period per each arm to determine if the combination dose regimen is tolerable. An interim 
analysis may be conducted when the last participant within any arm in Part 2 has 
completed at least one cycle of the combination treatment to support a regulatory 
submission. 
3.1.1. 
Dose Escalation Reviews 
Dose escalation meetings will be held to discuss dose escalation decisions after all 
participants (3 or 6 participants following a 3+3 dose-escalation procedure) in the initial 
dosing cohort complete the DLT evaluation period of the first 21 days of intervention. 
3 + 3 Dose Escalation: Dose-escalation will follow a 3 + 3 dose-escalation procedure as 
shown in Table 1. Evaluation of available safety data from at least 3 participants who 
have completed a minimum of 21 days (1 cycle: 21 days) is required to start the next dose 
cohort. Refer to Table 1 for more details. Dose levels to be tested in the study are 
provided in Table 2, Table 3, and Table 4. 
GSK may consult with safety and efficacy evaluation committee as needed. Safety and 
efficacy evaluation committee will propose GSK necessity of additional participant. 


 
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Table 1 
3 + 3 Dose-Escalation Guidelines 
Number of Participants with DLT at a Given 
Dose Level 
Action 
0 out of 3 participants 
Escalate to next dose level 
1 out of 3 participants 
Accrue 3 additional evaluable participants at 
current dose level for a total of 6 evaluable 
participants 
• 
If 0 of the additional 3 participants 
experience a dose-limiting toxicity (DLT), 
proceed to next dose level. 
• 
If 1 or more participants experience a 
DLT, the dose-escalation is stopped 
1 out of 6 participants 
Escalate to next dose level 
2 or more participants in a dosing cohort (up to 6 
participants) 
Dose-escalation will be stopped. 
Table 2 
Dose Levels for Part 1 
Dose Level 
GSK2857916 (mg/kg) 
0, starting dose 
2.5 
1 
3.4 
Table 3 
Dose Levels for Part 2 Arm A 
Dose Level 
GSK2857916 (mg/kg) 
0, starting dose 
2.5 
Table 4 
Dose Levels for Part 2 Arm B 
Dose Level 
GSK2857916 (mg/kg) 
0, starting dose 
2.5 (C1) and 1.9 (C2+) 
 
3.1.1.1. 
Displays to Be Created for Dose Escalation Review 
For the dose escalation meeting, data listings will be provided by DML in Excel 
spreadsheets based on the enrolled population. Details of the planned displays are 
presented in Dose Escalation Plan. 
3.2. 
Primary Analyses 
A primary analysis will be conducted to evaluate safety, efficacy and PK profiles by the 
data cut-off performed after both EOT and the completion of AE and SAE collection 
(i.e., 70 days after the last dose of study treatment) for last participant in Part 1. 
A primary analysis will be conducted per arm to evaluate safety, efficacy and PK profiles 
by the data cut-off performed after both EOT and the completion of AE and SAE 
collections (i.e., 70 days after the last dose of study treatment) for last participant in Part 
2. 


 
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The later of the primary analyses for Arm A and Arm B in Part 2 will be the final 
analysis for the entire study. 
 


 
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4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
Screened 
• All participants who were screened for eligibility 
• Study Population 
Enrolled 
• All participants who passed screening and 
entered the study. 
• Note screening failures (who never passed 
screening even if rescreened) and subjects 
screened but never enrolled into the study are 
excluded from the Enrolled population as they 
did not enter the study. 
• Study Population 
All Treated 
• All eligible subjects who receive at least 1 dose 
of study treatment. An incorrect treatment 
schedule or drug administration or an early 
termination of treatment will not result in 
exclusion of subjects from this population. 
• Study Population 
• Safety 
• Efficacy 
• Immunogenicity 
DLT Evaluable 
• All subjects fulfilling the ‘All Treated’ population 
criteria and having completed a minimum of 21 
days or experienced a DLT before 21 days. 
Subjects who have been withdrawn from the 
study for reasons other than toxicity but prior to 
the 21-day DLT observation period are not 
included in this population 
• Summary of DLT 
Pharamacokinetic 
(PK) 
• All subjects in the ‘All Treated’ population who 
had at least 1 non-missing PK assessment 
(Non-quantifiable ([NQ] values will be 
considered as non-missing values).  
• PK 
Pharmacodynamic 
(PD) 
• All subjects in the ‘All Treated’ population from 
whom at least one PD sample was obtained, 
analysed, and was measurable. 
• PD 
 
4.1. 
Protocol Deviations 
Important protocol deviations related to study inclusion/exclusion criteria, conduct of the 
trial, patient management, or patient assessment will be summarised and all protocol 
deviations, including both major and minor, will be listed. The classification of important 
protocol deviations includes AE/SAE, disallowed devices, disallowed medications, 
inclusion/exclusion criteria, informed consent, IP administration/study treatment, 
procedures/tests, and withdrawal criteria. The protocol deviation terms are detailed in the 
Protocol Deviation Specification. 
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Specification. 
o Data will be reviewed prior to database lock to ensure all important deviations are 
captured and categorised on the protocol deviations dataset. 
o This dataset will be the basis for the summaries and listings of protocol 
deviations. 


 
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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. 
There is no Per-Protocol Population for this study. Protocol deviations will not be used to 
determine membership in any particular study population for this study. 


 
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5. 
CONSIDERATIONS FOR DATA ANALYSES AND DATA 
HANDLING CONVENTIONS 
5.1. 
Study Treatment & Sub-group Display Descriptors 
This is a single-arm, dose escalation study of GSK2857916. In the data displays 
GSK2857916 will be abbreviated as GSK916. Data will be listed and summarised per the 
GSK reporting standards whenever applicable.  
5.2. 
Baseline Definitions 
For all endpoints (except as noted in baseline definitions) the baseline value will be the 
latest pre-dose assessment within 21 days prior to first dose with a non-missing value, 
including those from unscheduled visits. If time is not collected, Day 1 assessments are 
assumed to be taken prior to first dose and used as baseline. For laboratory data, baseline 
will be the latest non-missing pre-dose value. For PD assessments, only the Cycle 1 Day 
1 pre-dose measurement will be used as baseline. If there are multiple assessments on the 
same day, the mean will be used as the baseline value. 
Unless otherwise stated, if baseline data is missing no derivation will be performed and 
baseline will be set to missing. 
Parameter 
Study Assessments Considered as 
Baseline 
Baseline Used in 
Data Display 
Screening 
(within 21 days 
prior to first dose) 
Day 1 (Pre-Dose) 
Efficacy 
Disease assessment 
X 
 
Screening visit 
Safety 
Laboratory 
X 
X 
Latest up to Day 1 
Vital Signs  
X 
X 
Latest up to Day 1 
ECG 
X 
X 
Latest up to Day 1 
 
5.2.1. 
Change from baseline 
Change from baseline is calculated as: 
• 
For records occurring after baseline: (visit value) – baseline value. 
Percent change from baseline is calculated as: 
• 
For records occurring after baseline: ((change from baseline) / baseline value) * 100 
If either the baseline or visit value is missing, the change from baseline and/or percent 
change from baseline is set to missing as well. 


 
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5.3. 
Multicenter Studies 
Data from all participating centres will be pooled prior to analysis. 
It is anticipated that subject accrual will be spread thinly across centres and summaries of 
data by centre would be unlikely to be informative and will not, therefore, be provided. 
5.4. 
Examination of Covariates, Other Strata and Subgroups 
5.4.1. 
Covariates and Other Strata 
All analyses are descriptive or unadjusted. No analyses are planned to adjust for any 
covariate and prognostic factor. 
5.4.2. 
Examination of Subgroups 
No subgroup analysis will be performed. 
5.5. 
Multiple Comparisons and Multiplicity 
No formal statistical comparison will be performed; therefore, no adjustments for 
multiple comparisons or multiplicity are planned. 
5.6. 
Other Considerations for Data Analyses and Data Handling 
Conventions 
Other considerations for data analyses and data handling conventions are outlined in the 
appendices: 
Section 
Component 
14.3 
Appendix 3: Assessment Windows 
14.4 
Appendix 4: Study Phases and Treatment Emergent Adverse Events 
14.5 
Appendix 5: Data Display Standards & Handling Conventions 
14.6 
Appendix 6: Derived and Transformed Data 
14.7 
Appendix 7: Reporting Standards for Missing Data 
14.8 
Appendix 8: Values of Potential Clinical Importance 
 


 
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6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Study Population Analyses 
The study population analyses will be based on All Treated population, unless otherwise 
specified. 
Study population analyses including analyses of subject’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
anti-cancer therapies, and exposure and treatment modification will be based on GSK 
Core Data Standards. Details of the planned displays are presented in Appendix 10: List 
of Data Displays. The study population analyses will also be performed by dose (cohort) 
where necessary. 
6.2. 
Disposition of Subjects 
A summary of the number of subjects in each of the analysis populations described in 
Section 4 will be provided. In addition, a summary of screening status and reasons for 
screen failure will be provided using all screened population. A separate summary for 
exclusions from each study population will be displayed. A listing of subjects excluded 
from analysis populations will also be provided. 
 
A summary of subject status and reasons for study withdrawal will be provided. This 
display will show the number and percentage of subjects who withdrew from the study, 
including primary reasons for study withdrawal. Reasons for study withdrawal will be 
presented in the order they are displayed in the eCRF. 
 
A summary of study treatment status will be provided. This display will show the number 
and percentage of subjects who discontinued study treatment and a summary of the 
primary reasons for discontinuation of study treatment. Reasons for study treatment 
discontinuation will be presented in the order they are displayed in the eCRF. A listing of 
study treatment discontinuation will be generated. The listing will include last dose date 
and reasons for study treatment discontinuation. 
6.3. 
Demographic and Baseline Characteristics 
The demographic characteristics (e.g., age, race, ethnicity, sex, baseline height, baseline 
body weight and baseline BMI calculated as body weight in kilograms divided by 
squared height in m2) will be summarised and listed. Age, height, weight, and BMI will 
be summarised using the mean, standard deviation, minimum, median, and maximum. 
The count and percentage will be computed for sex and ethnicity. 
 
Race and racial combinations as well as age ranges (Adult (18-64 years), >=65-84 years, 
>=85 years; <18 years, 18-<65 years, 65-<75 years, >=75 years) will also be summarised 
and listed. 
 
Disease characteristics at initial diagnosis (e.g. time since initial diagnosis in years, stage 
at initial diagnosis, date of initial diagnosis) and screening will be listed. 


 
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Separate summaries of disease characteristics at initial diagnosis and screening will be 
provided. Disease characteristics for multiple myeloma subjects at screening, including 
stage, lines of prior therapy regimens, type of multiple myeloma, myeloma light chain 
and myeloma immunoglobulin will be summarised and listed.  
Medical conditions present at screening will be listed and will be summarised by past and 
current. 
 
Genetic characteristics for multiple myeloma subjects at screening will be summarised 
and listed. Cytogenetic risk for multiple myeloma subjects at screening will be 
summarised. A subject is considered as having high cytogenetic risk if the subject has 
any of the following cytogenetics: t(4;14), 17p13del, t(14;16). 
 
Substance use, including smoking history and alcohol use, will be listed.  
 
Prior and follow-up anti-cancer therapy will be coded using the GSK Drug code 
dictionary then summarised by type of therapy and listed. A listing of prior anti-cancer 
therapy will show the relationship between ATC Level 1 and verbatim text. A summary 
of the best response to the most recent prior anti-cancer therapy will be provided. A 
summary of the number of prior anti-cancer therapy regimens will also be produced. 
 
Anti-cancer radiotherapy will be listed. Prior cancer and non-cancer related surgeries will 
be summarised. Prior, on treatment, and follow-up cancer and non-cancer related 
surgeries will be listed. A summary and listing of Stem Cell Transplant will be provided. 
6.4. 
Extent of Exposure 
Extent of exposure to GSK2857916 will be summarised. 
 
The number of cycles administered to study treatment will be summarised with mean, 
median, standard deviation, minimum, and maximum. The number and percentages of 
subjects who received a given number of cycles (<=4, >4 cycles) will be reported. Note 
that the cycle will not be counted when the administration is interrupted/delayed. 
 
Cumulative actual dose (sum of dose at each cycle) and dose intensity per cycle 
(mg/kg/cycle) will be summarised using mean, median, standard deviation, minimum, 
and maximum by overall, as well as dose delivered by cycle. The dose intensity (mg/kg/3 
weeks), which is calculated as the cumulative actual dose (mg/kg) divided by expected 
duration of exposure in 3 weeks (Last Dose date – First Dose date + 21)/21), will also be 
summarised. A by-subject summary listing of data on exposure to all study treatments 
will be produced. 
 
Dose reductions will be summarised by number of reductions and reasons for reductions. 
Dose delays will be summarised by number of delays, reasons for the delays, and delay 
duration (days). The number and percentage of the delays for duration intervals of 1-21, 
22-42, and >42 days will be computed. Time to first delay will be summarised; first delay 
is defined as the first dose delay or first dose restarted after skipped dosing. Primary 
reasons for dose reductions and dose delays will also be summarised by overall. 
 


 
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Duration of delays is defined as period from the expected start date of dose to actual start 
date of current dose. Calculation: (actual start date of current dose - expected start date of 
dose). Expected start date of dose = actual start date of previous dose + 21. 
 
Incomplete infusions and infusion interruptions will be summarised by number and 
reason for incomplete or interrupted infusion. 
 
The summaries of dose modifications will be provided. All the dose reductions, infusion 
interruptions, incomplete infusions and dose delays will be listed. 
 
The duration of exposure to study treatment (from first day to last day of treatment) will 
be calculated and summarised using mean, median, standard deviation, minimum, and 
maximum. A swimmer plot of duration of treatment including best response (PR, VGPR, 
CR, sCR, MR, SD, PD) and study status will be provided, where PR, VGPR, CR, sCR, 
MR, SD, and PD stand for partial response, very good partial response, complete 
response, stringent complete response, minimal response, stable disease, and progressive 
disease, respectively.  
6.5. 
Concomitant Medications 
Concomitant medications will be coded using GSK Drug coding dictionary, summarised, 
and listed. The summary of concomitant medications will show the number and 
percentage of subjects taking concomitant medications by Ingredient. Multi-ingredient 
products will be summarised by their separate ingredients rather than as a combination of 
ingredients. Anatomical Therapeutic Chemical (ATC) classification Level 1 (Body 
System) information will be included in the dataset created but will not appear on the 
listing or summary. 
 
In the summary of concomitant medications, each subject is counted once within each 
unique ingredient. For example, if a subject takes Amoxycillin on two separate occasions, 
the subject is counted only once under the ingredient “Amoxycillin”. In the summary of 
concomitant medications, the ingredients will be summarised by the base only, using 
GSK Drug coding dictionary. Note: In order to be considered a concomitant medication, 
the concomitant medication must have been taken at some point during the on-treatment 
window. 
 
Prophylactic medication for infusion-related reactions and prophylactic topical eye 
medications will be summarised by drug class and drug name and eye medications will 
be listed. In addition, the percentage of duration of exposure that was on prophylactic 
steroid eye drop use will also be summarised as below. 
 
100*((Total number of days during treatment period on which subject exposed to 
concomitant medications identified as Steroid Eye Drops)/(Duration of treatment period)) 
 
Blood products or blood supportive care products with onset date within the on-treatment 
window will be included in the summary tables and listings. The frequency and 
percentage of subjects using these products after the start of study treatment will be 


 
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provided. Supporting listings will also be provided. Administration of on-treatment stem 
cell mobilization products will also be provided in a listing. 
 
Prior medications will be listed. 


 
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7. 
EFFICACY ANALYSES 
7.1. 
Primary Efficacy Analyses 
No primary efficacy analysis is planned in the study. 
7.2. 
Secondary Efficacy Analyses 
The secondary efficacy analyses will be performed by dose (cohort). 
7.2.1. 
Endpoint / Variables 
7.2.1.1. 
Unconfirmed and Confirmed Responses 
The hierarchy of response classifications from high to low is as follows: sCR, CR, 
VGPR, PR, MR, SD, PD, and NE. Response was assessed according to the IMWG 
Response Criteria [Kumar, 2016] (See Appendix 12: International Myeloma Working 
Group Uniform Response Criteria for Multiple Myeloma). 
The definitions and details to derive confirmed response are outlined below. For 
confirmed response derivations, only responses assessments from the start of treatment 
up to the start of new anti-cancer therapy will be considered. 
Unconfirmed Response (Without confirmation) 
Response assessments as provided by the investigator. 
Confirmed Response (With confirmation) 
The derivation of confirmed response shall be based on the algorithm specified in Table 
5. 
Table 5 
Response confirmation algorithm 
# Response at 
the First Time 
Point 
Response at Subsequent Disease 
Assessment1 
Confirmed 
Response at the 
First Time Point 
Date of 
Confirmed 
Response 
1 sCR 
sCR 
sCR 
First Time Point 
2 sCR 
CR 
CR 
First Time Point 
3 CR 
sCR/CR 
4 sCR/CR 
VGPR 
VGPR 
First Time Point 
5 VGPR 
sCR/CR/VGPR 
6 sCR/CR/VGP
R 
PR 
PR 
First Time Point 
7 PR 
sCR/CR/VGPR/PR 
8 sCR/CR/VGP
R/PR 
MR 
MR 
First Time Point 
9 MR 
sCR/CR/VGPR/PR/MR 
10 sCR/CR/VGP
R/PR/MR 
SD 
SD 
First Time Point 


 
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11 sCR/CR/VGP
R/PR/MR 
PD (any reason) 
 
OR 
No subsequent disease assessment: 
subject died or discontinued study 
or started new anti-cancer therapy 
before further adequate disease 
assessment 
NE 
First Time Point 
12 PD (due to 
reasons other 
than imaging, 
i.e., 
plasmacytoma 
or bone lesion) 
PD (any reason) including PD after 
initiation of new anti-cancer therapy 
 
OR 
No subsequent disease assessment: 
subject died due to PD before further 
adequate disease assessment 
(including death due to PD after 
initiation of new anti-cancer therapy) 
PD 
First Time Point 
13 PD (due to 
reasons other 
than imaging, 
i.e., 
plasmacytoma 
or bone lesion) 
sCR/CR/VGPR/PR/MR/SD 
 
OR 
No subsequent disease assessment: 
subject died due to reasons other 
than PD before further adequate 
disease assessment 
 
OR 
No subsequent disease assessment: 
subject discontinued study before 
further adequate disease assessment4 
NE 
First Time Point 
14 sCR/CR/VGP
R/PR/MR/PD 
(due to 
reasons other 
than imaging, 
i.e., 
plasmacytoma 
or bone lesion) 
No subsequent disease assessment: 
subject has not died, discontinued from 
study or (except for PD) started new 
anti-cancer therapy; but as yet has no 
further adequate disease assessments 
Unconfirmed 
sCR/CR/VGPR/PR/M
R/PD. 
 
Will be categorized 
as NE for final ORR 
analysis. 
First Time Point 
15 SD2 
Any 
 
OR 
No subsequent disease assessment 
SD 
First Time Point 
16 PD due to  
imaging 
(plasmacytom
a or bone 
lesion)3 
Any 
 
OR 
No subsequent disease assessment 
PD 
First Time Point 
17 NE or missing 
Any 
 
OR 
No subsequent disease assessment 
NE 
First Time Point 
1. Subsequent disease assessment is defined as the next adequate (not missing or NE) disease 
assessment following the first timepoint before (or on the same date of) start of new anti-cancer 


 
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therapy except for confirmation of PD, for which PD or death due to PD after new anti-cancer 
therapy are considered for confirmation of PD. No minimal time interval is required for the 
subsequent disease assessment, but a different sample is required for confirmation. 
2. SD does not need to be confirmed. 
3. PD due to imaging (i.e., plasmacytoma or bone lesion) does not need to be confirmed. 
4. Where criteria are not mutually exclusive, take the first that applies. 
 
7.2.1.2. 
Best Overall Response (BOR) 
Best Overall Response (Best response) will be derived from confirmed responses. 
7.2.1.3. 
Overall Response Rate (ORR) 
ORR is defined as the percentage of participants with a confirmed PR or better (i.e. PR, 
VGPR, CR and sCR) of best response, according to the IMWG Response Criteria 
[Kumar, 2016]. The number and percentage of participants with best overall response 
(BOR) in the following response categories will be summarised by dose level: sCR, CR, 
VGPR, PR, overall response (sCR+CR+VGPR+PR), minimal response (MR), stable 
disease (SD), progressive disease (PD), and not evaluable (NE). 
7.2.1.4. 
Clinical Benefit Rate (CBR) 
CBR is defined as the percentage of participants with a confirmed MR or better (i.e. MR, 
PR, VGPR, CR and sCR) of best response, according to the IMWG Response Criteria 
[Kumar, 2016]. 
7.2.2. 
Summary Measure for ORR and CBR 
Summary of confirmed ORR and CBR will be provided. A two-sided exact 95% CI for 
ORR and CBR will also be provided. Participants with unknown or missing response will 
be treated as non-responders, i.e., these participants will be included in the denominator 
when calculating percentages of response. 
7.2.3. 
Population of Interest  
The analyses for ORR and CBR will be based on the All Treated population, unless 
otherwise specified. 
7.2.4. 
Statistical Analyses / Methods 
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK data standards and statistical principles. 
Unless otherwise specified, endpoints / variables defined in Section 7.2.1 will be 
summarised using descriptive statistics, graphically presented (where appropriate), and 
listed. Listings of investigator assessed responses, extramedullary disease evaluation, 
disease assessment scan, and skeletal survey will be provided. 


 
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8. 
SAFETY ANALYSES 
The safety analyses will be based on the All Treated population, unless otherwise 
specified. The safety analyses will also be performed by dose (cohort) where necessary. 
The safety analyses associated with Covid-19 will also be performed. 
8.1. 
Adverse Events Analyses 
Adverse events analyses including the analysis of adverse events (AEs), Serious (SAEs), 
treatment emergent AEs, and other significant AEs will be based on GSK Core Data 
Standards. Details of the planned analysis are provided in Appendix 10: List of Data 
Displays. Adverse events analyses will include On-treatment AEs unless otherwise 
specified. Dose limiting toxicity (DLT) will also be summarised and listed according to 
GSK Oncology Data Standards.  
AEs aside from corneal events associated with GSK2857916 will be graded by the 
investigator according to the National Cancer Institute - Common Toxicity Criteria for 
Adverse Events (NCI-CTCAE) v4.03. AEs will be coded to the Preferred Term (PT) 
level using the Medical Dictionary for Regulatory Affairs (MedDRA). Only AEs graded 
by NCI-CTCAE will be summarised unless otherwise specified. 
An overview summary of AEs, including counts and percentages of subjects with any 
AE, AEs related to GSK2857916, Grade 3/4 AEs, Grade 3/4 AEs related to 
GSK2857916, AEs leading to dose reduction of GSK2857916, AEs leading to dose delay 
of GSK2857916, AEs leading to incomplete infusion, AEs leading to infusion 
interruption, AEs leading to permanent discontinuation of GSK2857916, any SAEs, 
SAEs related to GSK2857916, fatal SAEs, and fatal SAEs related to GSK2857916 will 
be produced. 
A summary of non-serious AEs that occurred in greater than or equal to 2 subjects will be 
reported. This summary will contain the number and percentage of subjects with the 
event and the number of occurrences of the events. The summary table will be displayed 
by System Organ Class (SOC) and Preferred Term (PT). 
The relationship between MedDRA SOC, PT, and Verbatim Text will be displayed. 
A summary of number and percentage of subjects with any AEs by maximum grade will 
be produced separately by both SOC and PT and by PT only; however ocular related AEs 
(corneal, keratopathy, microcyst, haze, opacity) by maximum grade will be summarised 
separately because the GSK grading scale is used for ocular related AEs. AEs will be 
sorted by SOC (by PT) in descending order of total incidence. The summary will use the 
following algorithms for counting the subject: 
• 
Preferred term row: Subjects experiencing the same AE preferred term several 
times with different grades will only be counted once with the maximum grade. 
• 
Any event row: Each subject with at least one AE will be counted only once at the 
maximum grade no matter how many events they have. 


 
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In addition, the frequency and percentage of AEs (all grades) will be summarised and 
displayed in descending order of total incidence by PT.  
Summary of study treatment-related AEs will be provided. A study treatment-related AE 
is defined as an AE for which the investigator classifies the relationship to study 
treatment as “Yes”. A worst case scenario approach will be taken to handle missing 
relatedness data, i.e. the summary table will include events with the relationship to study 
treatment as ‘Yes’ or missing. The summary tables by maximum grade will be displayed 
in descending order of total incidence by PT.  
All AEs and treatment emergent AEs will be listed. Additionally, a listing of subject IDs 
for each individual AE will be produced. 
A summary of the number of subjects with suspected, probable, and confirmed COVID-
19 infections will be provided. Additionally, the exposure adjusted incidence rate of all 
adverse events and adverse events occurring in >2 subjects pre, during, and post COVID-
19 pandemic will be summarised. An adverse event will be defined as occurring during a 
time block if the start date is within the start and end date of the time block. The 
calculation for exposure adjusted incidence rate is the following: 
Exposure adjusted incidence rate (rate/100 PY) = (number of subjects with the adverse 
event during the time block/total exposure duration across all subjects)*100 
where exposure duration for each subject is calculated as: 
• (treatment stop date1 – treatment start date2 + 1)/365.25 for subjects who do not 
experience the event 
• (start date of AE – treatment start date2 + 1)/365.25 for subjects that do 
experience the event 
1 minimum of 70 days after ending study therapy, last contact date, death, or end of time 
block.  
2 or start date of time block, whichever occurs later. 
The details of the planned displays are provided in Appendix 10: List of Data Displays. 
8.2. 
Adverse Events of Special Interest Analyses 
Adverse events of special interest (AESI) for GSK2857916 are corneal events, 
thrombocytopenia, and infusion related reactions. Severity of corneal events associated 
with GSK2857916 and related ophthalmic exam findings or visual acuity will be graded 
using GSK scale. The severity of other AESI will be graded via CTCAE version 4.03. A 
comprehensive list of MedDRA terms based on the safety review team (SRT) will be 
used to identify each type of event. 
Summaries of the number and percentage of subjects with these events will be provided 
for each type of event separately by preferred term and maximum grade. The time of 
onset and duration of first occurrence of each type of event will be summarised using the 
summary statistics mean, standard deviation, median, minimum value, and maximum. 


 
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The number and percentage of subjects who have time of onset of first occurrence (1-21, 
22-42, 43-63, >63 days for CTCAE grading and 1-21, 22-42, 43-63, 64-105, and >105 
for GSK scale grading) will be summarised. The number and percentage of subjects who 
have duration of first occurrence (1-21, 22-42, >42 days) will be summarised. 
 
The summary of event characteristics will also be provided, including number of subjects 
with any event, number of events, number of subjects with any event that is serious, 
number of subjects with any event that is related to study treatment, number of 
occurrences (One, Two, Three or more), maximum grade, and the action taken for the 
event. The percentage will be calculated in two ways, one with number of subjects with 
event as the denominator and the other with total number of subjects as the denominator.  
The worst-case approach will be applied at subject level for the maximum grade, i.e. a 
subject will only be counted once as the worst case from all the events experienced by the 
subject. For action taken to an event, a subject will be counted once under each action, 
e.g. if a subject has an event leading to both study treatment discontinuation and dose 
reduction, the subject will be counted once under both actions. 
 
Corneal events (GSK Scale) by grade and visit, corneal event (GSK Scale) overview and 
action taken with study treatment for corneal events (GSK Scale) by visit will be 
summarized. Also, corneal events (CTCAE Scale) overview will be summarized. 
All AEs of special interest will be listed separately. The details of the planned displays 
are provided in Appendix 10: List of Data Displays. 
8.3. 
Deaths and Serious Adverse Events 
In the event that a subject has withdrawn consent, no data after the withdrawal of consent 
date from this subject including death is supposed to appear in the database, which should 
be part of the data cleaning process. All deaths will be summarised based on the number 
and percentage of subjects. This summary will classify subjects by primary cause of 
death. A supportive listing will be generated to provide subject-specific details on 
subjects who died.  
All SAEs will be tabulated based on the number and percentage of subjects who 
experienced the event. The frequency and percentage of SAEs will be summarised in 
descending order of total incidence by SOC and PT. Separate summaries will also be 
provided for study treatment-related SAEs. A study treatment-related SAE is defined as 
an SAE for which the investigator classifies the relationship to study treatment as “Yes”. 
A worst case scenario approach will be taken to handle missing data, i.e. the summary 
table will include events with the relationship to study treatment as ‘Yes’ or missing.  
SAEs are included in the listing of all adverse events. Separate supportive listings with 
subject-level details will be generated for 
• 
Fatal SAEs  
• 
Non-fatal SAEs 


 
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8.4. 
Adverse Events Leading to Discontinuation and Dose 
Modification of Study Treatment 
The following categories of AEs and AESIs will be summarised separately in descending 
order of total incidence by PT only and separate supportive listings will be generated with 
subject level details for those subjects: 
• 
AEs Leading to Permanent Discontinuation of GSK2857916 
• 
AEs Leading to Dose Delays 
• 
AEs Leading to Dose Reductions 
Also, the following supportive listings will be generated with subject level details for 
those subjects: 
• 
AEs Leading to Infusion interruptions 
• 
AEs Leading to Incomplete infusions 
8.5. 
Clinical Laboratory Analyses 
Laboratory evaluations including the analyses of Chemistry laboratory tests, Hematology 
laboratory tests, Urinalysis, and liver function tests will be based on GSK Core Data 
Standards. The details of the planned displays are in Appendix 10: List of Data Displays. 
Clinical Laboratory Tests are listed in Table 6. 


 
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Table 6 
 List of Clinical Laboratory Tests 
 
 
Hematology1 
Platelet Count  
RBC Indices: 
Automated WBC Differential: 
Red blood cell (RBC) 
Count 
Mean corpuscular volume (MCV) 
Neutrophils 
White blood cell (WBC) 
Count (absolute)  
Mean corpuscular hemoglobin (MCH) 
Lymphocytes 
Reticulocyte Count 
Mean corpuscular hemoglobin concentration 
(MCHC) 
Monocytes 
Hemoglobin 
 
Eosinophils 
Hematocrit 
 
Basophils 
Clinical Chemistry1 
Blood urea nitrogen 
(BUN) 
Potassium 
Aspartate 
aminotransferase (AST) 
Total and direct bilirubin 
Creatinine   
Chloride 
Alanine 
aminotransferase (ALT) 
Uric Acid 
Glucose 
Spot urine (albumin / 
creatinine ratio) 
Gamma glutamyl 
transferase (GGT) 
Albumin  
Sodium  
Calcium  
Alkaline phosphatase 
(ALP) 
Total Protein  
Magnesium  
Phosphorous  
Creatine kinase (CK) 
Lactate dehydrogenase (LDH) 
Estimated Glomerular 
filtration rate (eGFR) 
 
 
 
Urine1 
Routine Urine Dipstick (Urinalysis required if blood or protein is detected by dipstick) 
Specific gravity 
pH, glucose, protein, blood and ketones by dipstick 
Microscopic examination (if blood or protein is abnormal) 
Other Safety 
C-reactive protein (CRP)1 
Troponin I or T4 
B-type natriuretic peptide (BNP)4 


 
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Table 6 
List of Clinical Laboratory Tests (cont.) 
PK/ADA  
Pharmacokinetics (PK)2 
Anti-Drug Antibodies (ADA)2, 3 
Optional Testing 
Genetics2 
Disease Evaluation Laboratory Tests 
Urine Protein 
Electrophoresis 
(UPEP)1 
urine Immunofixation1 
24-hour urine 
collection for M-
protein1 
Calcium corrected for 
albumin (serum)
1 
Serum Protein 
Electrophoresis 
(SPEP)1 
Serum M-protein 
calculation1 
Serum 
Immunofixation1 
Beta2 macroglobulin1 
Serum Kappa, lambda 
free LC, FLC ratio1 
IgG, IgA, IgM. 
IgD and IgE only in 
participants with IgD or IgE 
myeloma 
  
 
Soluble BCMA 
(sBCMA) (Serum)2 
 
 
1. To be performed at local laboratory.   
  
3. Not needed at screening 
4. If not available from local laboratory, it can be performed at central laboratory. 
5. FISH testing at least for: t(4;14), t(14;16), 17p13del. BM samples from within 60 days prior to first dose are 
acceptable for FISH analysis. 
 
Laboratory grades will be reported using the National Cancer Institute-Common 
Terminology Criteria for Adverse Events (NCI-CTCAE) v4.03. 
Summary of change from baseline by scheduled visits using mean, median, standard 
deviation, minimum, and maximum will be provided. Count data will be used for 
automated WBC differential. 
Summaries of worst-case grade increase from baseline grade will be provided for all the 
lab tests that are gradable by CTCAE v4.03. These summaries will display the number 
and percentage of subjects with a maximum post-baseline grade increasing from their 
baseline grade. Any increase in grade from baseline will be summarised along with any 
increase to a maximum grade of 3 and any increase to a maximum grade of 4. 
Missing baseline grade will be assumed as grade 0. For laboratory tests that are graded 
for both low and high values, summaries will be done separately and labeled by direction, 
e.g. sodium will be summarised as hyponatremia and hypernatremia. 
CCI
CCI


 
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For lab tests that are not gradable by CTCAE v4.03, summaries of worst case changes 
from baseline with respect to normal range will be generated. Decreases to low, changes 
to normal or no changes from baseline, and increases to high will be summarised for the 
worst case post-baseline. If a subject has a decrease to low and an increase to high during 
the same time interval, then the subject is counted in both the “Decrease to Low” 
categories and the “Increase to High” categories.  
Separate summary tables for haematology, chemistry, and urinalysis laboratory tests will 
be produced. 
A supporting listing of laboratory data for subjects with any value of potential clinical 
importance will be provided. A separate listing of laboratory data with character values 
will also be provided. 
Detailed derivation of baseline assessment is specified in Section 5.2. 
Unless otherwise specified, the denominator in percentage calculation at each scheduled 
visit will be based on the number of subjects with non-missing value at each particular 
visit. 
A summary of worst case urinalysis results post-baseline relative to baseline will be 
generated. 
For lab tests that can be graded, values of grade 1 or above are defined as values of 
potential clinical concern. For lab test values that cannot be graded, values out of the 
normal range are defined as values of potential clinical concern.  
8.5.1. 
Analyses of Liver Function Tests (LFT) 
Summaries of hepatobiliary laboratory events including possible Hy’s law cases will be 
provided in addition to what has been described above.  
Possible Hy’s law cases are defined as any elevated ALT≥3×ULN, total 
bilirubin≥2×ULN and ALP<2×ULN/missing. Total bilirubin≥2×ULN can be within 28 
days following the ALT elevation and if direct bilirubin is available on the same day, it 
must be ≥ 35% of total bilirubin. ALP<2xULN/missing means the criteria is satisfied 
unless the ALP is ≥2xULN at any time of bilirubin elevation within the 28 days window.  
LFT patient profiles plots for subjects experiencing an ALT, AST, or total bilirubin of 
toxicity grade 2 or above will be produced. 
A scatter plot of maximum total bilirubin versus maximum ALT will be generated. Also, 
a scatter plot of maximum vs baseline for ALT will be produced. 
A Summary of Liver Monitoring/Stopping Event Reporting will be provided. The 
medical conditions data for subjects with liver stopping events will be listed. The 
substance use data for subjects with liver stopping events will be listed. 


 
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8.5.2. 
Analyses of Disease Evaluation 
Summaries of disease evaluation changes from baseline as well as disease evaluation 
worst case change from baseline will be provided. 
8.5.3. 
Analyses of eGFR 
Summaries of eGFR, changes from baseline in eGFR, as well as eGFR worst case 
changes from baseline will be provided. A supporting listing of subjects with values 
outside of normal range will be provided. 
8.6. 
Other Safety Analyses 
The analyses of non-laboratory safety test results including ECGs and vital signs will be 
based on GSK Core Data Standards, unless otherwise specified. Performance status 
(ECOG) will be summarised and listed and LVEF will be listed based on GSK Oncology 
Data Standard. The details of the planned displays are presented in Appendix 10: List of 
Data Displays. 
8.6.1. 
Performance Status 
ECOG performance status will be summarised at baseline and post-baseline scheduled 
visits. Summaries will use frequency and percentage of subjects at each planned 
assessment time. A summary of change from baseline by scheduled visits will be 
performed, as well as the worst-case post-baseline and the best case post-baseline 
changes during the study (improved, no change, deteriorated). 
A supporting listing will also be provided. 
8.6.2. 
ECG 
12-lead ECGs will be obtained using an ECG machine that automatically calculates the 
heart rate and measures PR, RR interval, QRS, QT and QTcF intervals. Baseline QTcF 
value is determined by Day 1 pre-dose QTcF result (either a single result or the mean of 
triplicate results). If these are not available, the screening ECG results should be used.  
The QTc values based on Fridericia formula will be rounded to the integer and the values 
will be categorized into the following ranges: Grade 0 (<450), Grade 1 (450-480), Grade 
2 (481-500), and Grade 3 (≥501).  
The QTc will be based on the collected value using Fridericia formula. The ECG results, 
increase in QTcF, and amount of increase from baseline value will be summarised. 
Listings of abnormal ECG findings and a listing of ECG values including Potential 
Clinical Importance will be provided. Potential clinical significance ranges are provided 
as follows: 
 
 


 
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ECG Parameter 
Units 
Clinical Concern Range  
Low          Upper 
Absolute 
QTc Interval 
msec 
             >481 
PR Interval 
msec 
<110         >220 
RR Interval 
msec 
<60         >120 
QRS Interval 
msec 
<75          >110 
Change from 
baseline 
QTc Interval 
msec 
             >30 
8.6.3. 
LVEF 
Absolute change from baseline in LVEF will be summarised by worst case post-baseline 
only. Only the post-baseline assessments that used the same method (ECHO) as the 
baseline assessments will be used to derive the change from baseline. The change from 
baseline will be categorized as follows: 
• No change or any increase 
• Any decrease 
• >0-<10 decrease 
• 10-19 decrease 
• >=20 decrease 
• >=10 decrease and >= LLN 
• >=10 decrease and < LLN 
• >=20 decrease and >= LLN 
• >=20 decrease and < LLN 
LVEF results will also be listed with subject level details including absolute change from 
baseline. 
8.6.4. 
Ocular Exams 
Ophthalmic exams are scheduled at screening, during the study, and follow-up period. 
The ocular findings from ophthalmic exams will be analysed as described below. 
 
1. From baseline to EOT visit, the following analysis will be 
performed: 
 
a. Best corrected visual acuity (BCVA): BCVA (logMAR score) at baseline, 
EOT visit, and last follow-up visit as well as worst and most frequent 
category (definite worsen, possible worsen, and no change/improved) of 
change from baseline will be summarised by eye (R/L) and subject (worse 
eye and better eye). BCVA for subjects with corneal finding will also be 
provided. The logMAR score is calculated as: 
 
logMAR score = -1 * (log10(Landolt ring value)) 
 
b. Intraocular Pressure (IOP): summary table of number (%) of subjects with 
IOP ≥ 22mm Hg anytime post-baseline. 


 
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c. Pupillary Exam: shift table (Normal to Abnormal) from baseline to worst 
post-baseline by subject (worse eye) 
d. Extraocular Muscle Movement: shift table (Full Intact: Yes to No) from 
baseline to worst post-baseline by eye (R/L) and subject (worse eye) 
e. External Exam: shift table (Ptosis: No to Yes) from baseline to worst post-
baseline by eye (R/L) and subject (worse eye) 
f. Lids/Lashes/Lacrimal System: shift table (Blepharitis/MGD: No to Yes) 
from baseline to worst post-baseline by eye (R/L) and subject (worse eye) 
g. Conjunctival Exam: 
i. 
shift table and summary table (Chemosis: Absent to Present; 
Bulbar Conjunctiva White and Quiet: Yes to No; Palpebral 
Conjunctiva within normal limits: Yes to No) from baseline to 
worst post-baseline by eye (R/L) and subject (worse eye) 
h. Sclera: shift table (Scleritis: No to Yes) from baseline to worst 
postbaseline by eye (R/L) and subject (worse eye) 
i. Corneal Exam: 
i. 
Corneal epithelium findings: 
1. Shift table from baseline to worst post-baseline by eye (R/L) 
and subject (worse eye) for Corneal epithelium (Normal to 
Abnormal) 
2. Summary and shift tables for Microcystic edema (No to Yes), 
Microcystic without edema (Yes/No), Subepithelial haze (No 
to Yes), Corneal neovascularization (No to Yes), Stroma 
(Normal to Abnormal), Active opacity (No to Yes), and Active 
edema (No to Yes). 
3. For punctate keratopathy, summary table of worst grade and 
most frequent grade across ocular exams by eye (R/L) and 
subject (worse eye) 
ii. 
Corneal endothelium findings: 
1. Shift table from baseline to worst post-baseline by eye 
(R/L) and subject (worse eye) for Corneal endothelium 
(Normal to Abnormal) 
2. Summary table by eye (R/L) and subject (worse eye) for 
presence of Descemet's folds and Endothelial lesion at any 
post-baseline ocular exam. 
j. Slit Lamp Exam: 
i. 
Shift table from baseline to worst post-baseline by eye (R/L) 
and subject (worse eye) for Anterior Chamber: Deep/Quiet (Yes 
to No); Iris: Flat, round and reactive (Yes to No); and Lens: 
Clear (Yes to No). 
ii. 
Summary tables of presence of iris findings ('Transillumination 
defect', 'Nodules', or 'Neovascularization') at any post-baseline 
ocular exam. 
iii. 
Shift table from baseline to worst post-baseline by eye (R/L) 
and subject (worse eye) for Nuclear sclerosis (No to Yes), 
Cortical cataract (No to Yes), and Posterior subcapsular cataract 
(No to Yes) 
iv. 
Summary tables of grade change in Cataract 


 
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k. FUNDUS Photograph: Shift table from baseline to worst post-baseline by 
eye (R/L) and subject (worse eye) for Vitreous normal in appearance (Yes 
to No), PVD (No to Yes), Vitreous cell (No to Yes), Vitreous haze (No to 
Yes), Optic nerve normal in appearance (Yes to No), and Retina normal in 
appearance (Yes to No). 
 
2. From EOT visit to last follow-up visit: To assess the change in corneal findings after 
discontinuation of study treatment, among eyes and subjects (worse eye) with exam 
finding at EOT visit worse than baseline, the following analyses will be performed. 
 
a. Summary of change (worsening, no change, improvement) from EOT to 
last follow-up visit based on categories defined below by eye (R/L) and 
subject (worse eye) 
b. Summary of number (%) of eyes and subjects (worse eye) that resolve 
(improve to baseline level or better based on categories defined below), 
and descriptive summary of time from EOT visit to resolution among 
eyes and subjects (worse eye) that resolved 
 
The parameters included in above analyses are: 
 
1. BCVA change from baseline in log MAR scale (< 0.12, ≥ 0.12 to < 0.3, ≥ 0.3) 
2. IOP (≥ 22mm Hg, <22mm Hg) 
3. Corneal epithelium (Normal/Abnormal), Punctate Keratopathy (None/Mild 
/Moderate/Severe), Microcystic edema (No/Yes), Microcystic without edema 
(No/Yes), Subepithelial haze (No to Yes), Corneal neovascularization (No to 
Yes), Stroma (Normal/Abnormal); Active opacity (No/Yes); Active edema 
(No/Yes) 
4. Corneal endothelium (Normal/Abnormal), Descemet's folds (No/Yes), 
Endothelial lesion (No/Yes) 
 
All summary and shift tables will be provided by eye (R/L) and worse eye or better eye. 
If both eyes are diagnosed as abnormal, subject is counted as abnormal (yes, present, or 
others).  
The ocular exam results are listed for the data related summary tables only. The details of 
the planned displays are provided in Appendix 10: List of Data Displays.  
8.6.5. 
Vital Signs 
Values of vital signs as well as the change from baseline will be summarised by 
scheduled visit using mean, median, standard deviation, minimum and maximum.  
In addition, vital sign values will be categorized as follows: 
• 
Systolic BP (mmHg):  
Grade 0 (<120), Grade 1 (120-139), Grade 2 (140-159) and Grade 3 (≥160) 
• 
Diastolic BP (mmHg):  
Grade 0 (<80), Grade 1 (80-89), Grade 2 (90-99), and Grade 3 (≥100) 


 
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• 
Heart rate (beats/min):  
<60, 60-100, and >100 
• 
Temperature (°C):  
≤35, >35-<38, ≥38 
Summaries of worst-case changes in vital signs from the baseline with respect to the 
categories defined above will be performed. The vital signs data will be listed. 
8.6.6. 
Anti-Drug Antibody  
For each subject, the anti-GSK2857916 (drug) binding antibody results and titers, and 
ADC and total antibody concentration will be listed for each assessment time point. The 
frequency and percentage of subjects with positive and negative anti-drug antibody will 
be summarised for each assessment and overall for each subject by dose cohort. The 
conclusive results will be based on the total antibody concentration. 
8.6.7. 
Pregnancies 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy for medical reasons will be recorded 
as an AE or SAE as described in the protocol. If subjects become pregnant while on the 
study, the information will be included in the narratives and no separate table or listing 
will be produced. 


 
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9. 
PHARMACOKINETIC ANALYSES 
9.1. 
Endpoint / Variables 
9.1.1. 
Drug Concentration Measures 
Refer to Appendix 5: Data Display Standards & Handling Conventions (Section 14.5.3 
Reporting Standards for Pharmacokinetic) 
9.1.2. 
Derived Pharmacokinetic Parameters 
Pharmacokinetic parameters will be calculated by standard non-compartmental analysis 
according to current working practices and using the currently supported version of 
WinNonlin. The parameters are listed in the following table: 
 
Parameter Parameter Description 
AUC(0-t) 
Area under the concentration-time curve from time zero to the time of the last 
quantifiable concentration (C(t)) will be calculated using the linear trapezoidal rule 
for each incremental trapezoid and the log trapezoidal rule for each decremental 
trapezoid 
AUC(0-τ) 
Area under the concentration-time curve during the dosing interval 
AUC(0-
∞) 
Area under the concentration-time curve extrapolated to infinity will be calculated 
as:  
AUC = AUC(0-t) + C(t) / lambda_z  
Cmax 
Maximum observed concentration, determined directly from the concentration-time 
data for each cycle.  For cys-mcMMAF, Cmax will not be derived when only 
predose and EOI samples were collected. 
tmax 
Time to reach Cmax, determined directly from the concentration-time data for each 
cycle 
t½ 
Apparent terminal half-life will be calculated as:  
t½ = ln(2) / lambda_z  
tlast 
Time of last observed quantifiable concentration  
CL 
Clearance  
Vss 
Volume of distribution at steady state  
λz, 
lambda_z 
Terminal phase rate constant  
 
All calculations of non-compartmental parameters will be based on actual sampling 
times. From the plasma concentration-time data, the following GSK2857916 (intact 
ADC, total antibody) and cys-mcMMAF PK parameters will be determined as data 
permit, for each dose of GSK2857916 and for each participant:  
1) After single dose: area under the plasma concentration-time curve (AUC(0-t), 
AUC(0-tau) and/or AUC(0-∞)), maximum observed plasma concentration 
(Cmax), time to Cmax (tmax), last time point where the concentration is above 
the limit of quantification (tlast), systemic clearance (CL), volume of distribution 


 
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at steady state (Vss), terminal phase elimination rate constant (λz), terminal phase 
half-life (t½).  
2) After repeat dose: concentration at end of infusion (Ceoi) after Cycles 3, 6, 9, and 
12 and concentration pre-dose (Ctrough) prior to Cycles 3, 6, 9, and 12 for 
accumulation ratio analysis. 
9.2. 
Population of Interest  
The secondary pharmacokinetic analyses will be based on the Pharmacokinetic 
population, unless otherwise specified. 
9.3. 
Statistical Analyses / Methods 
GSK2857916 (intact ADC and total antibody) and cys-mcMMAF concentration-time 
data will be listed for each participant and summarised by descriptive statistics at each 
time point by dose (cohort). Linear and semi-logarithmic individual plasma 
concentration-time profiles and mean and median profiles (when applicable) by 
GSK2857916 dose will be plotted for GSK2857916 (intact ADC and total antibody) and 
cys-mcMMAF. 
Pharmacokinetic parameters will be listed and summarised descriptively (mean, standard 
deviation, median, minimum, maximum, geometric mean, and the standard deviation of 
log-transformed parameters, CV% and 95% CI of log-transformed parameters) by dose 
cohort.  
9.3.1. 
Assessment of Accumulation Ratio 
To assess the extent of accumulation following GSK2857916 repeat dosing, the observed 
accumulation ratio (R0) for GSK2857916 intact ADC, total antibody, and cys-mcMMAF 
will be determined as a ratio of Ceoi at cycles 3, 6, 9, and 12 to Ceoi at Cycle 1 and as a 
ratio of Ctrough at Cycles 2, 5, 8, and 11 to Ctrough at Cycle 1. 
Subjects must receive the same dose as Cycle 1 without delay and receive the same dose 
for the previous 3 cycles relative to the cycle of interest to be included in this analysis 
(i.e. with dosing delays of ≤3 days).  
R0(Ceoi) = Ceoi(Cx) / Ceoi(C1); x=3, 6, 9, 12 
R0(Ctrough) = Ctrough(Cx) / Ctrough*(C1); x=2, 5, 8, 11 
Ctrough(Cx)=Pre-dose at Cycle(x+1) 
Ctrough*(C1)=Pre-dose at Cycle 2 Day 1 (trough of C1) 
Accumulation ratio of Ceoi and Ctrough will be summarised using descriptive statistics 
by planned initial dose level, graphically presented (where appropriate), and listed.  
Additionally, geometric mean and 95% CI will be calculated by taking the exponential 
for the mean and 95% CI of the difference in log transformed concentration between the 
visit and Cycle 1 Day 1. These parameters will be summarized and plotted. 
Details of the planned displays are provided in Appendix 10: List of Data Displays and 
will be based on GSK Data Standards and statistical principles. 


 
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10. 
POPULATION PHARMACOKINETIC (POPPK) 
ANALYSES 
The primary goal of this analysis is to characterize the population pharmacokinetics of 
GSK2857916 and associated analytes after intravenous of GSK2857916 in participants 
with multiple myeloma, as data permit. The influence of subject demographics, baseline 
characteristics, including disease activity, and co-medication on the pharmacokinetics of 
GSK2857916 in this population may be investigated. The individual subject PK 
parameters may be estimated and documented for the purposes of any subsequent 
exposure-response (PK/PD) analyses. The analysis may be performed by CPMS and 
reported separately. 


 
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13. 
REFERENCES 
Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group 
consensus criteria for response and minimal residual disease assessment in multiple 
myeloma. The Lancet Oncology. 2016;17: e328-e346. 


 
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14. 
APPENDICES 
14.1. 
Appendix 1: Protocol Deviation Management and Definitions 
for Per Protocol Population 
14.1.1. 
Exclusions from Per Protocol Population 
This study does not have a per protocol population. 
 
 


 
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14.2. 
Appendix 2: Schedule of Activities 
Refer to Protocol Section 1.3, Schedule of Activities (SoA). 


 
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14.3. 
Appendix 3: Assessment Windows 
14.3.1. 
Definitions of Assessment Windows for Analyses 
No assessment window will be applied. 


 
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14.4. 
Appendix 4: Study Phases and Treatment Emergent 
Adverse Events 
14.4.1. 
Study Phases 
Assessments and events will be classified according to the time of occurrence relative to 
date/time of first dose of study treatment. 
Study Phase 
Definition 
Pre-Treatment  
Date ≤ Study Treatment Start Date 
On-Treatment 
Study Treatment Start Date < Date 
On-Treatment AEs 
Study Treatment Start Date < Date ≤ Study Treatment Stop Date + 70 days 
 
For assessment or event on the first dosing day, whether it is Pre-Treatment or On-
Treatment should be based on time if available. If time is not available, the first dosing 
day (Day 1) is considered Pre-Treatment for ECOG, ECG, vital signs, liver events, lab 
tests, cardiac scan, and other safety domains, and On-Treatment for adverse events and 
concomitant medications. 
 
14.4.1.1. 
Study Phases for Concomitant Medication and Blood and Blood 
Supportive Care Product 
Concomitant Medication and Blood and Blood Supportive Care and Stem Cell 
Mobilization Product start and end dates will be assigned to study time periods in relation 
to first dose of study treatment as defined below. The start date references time flag 
variables and end date reference time flag variables will be added to the concomitant 
medications and blood and blood supportive products datasets, respectively. 
 
• Start relative to treatment: Assign to 'BEFORE' if start date is prior to study 
treatment start date or if subject has not taken any study treatment or (start date is 
missing and end date is before study treatment start date). Else assign to 
'DURING' if the start date falls into the on-treatment period as defined above or if 
subject is ongoing (not all study treatment discontinuation records completed) or 
start date is missing. Else assign to 'AFTER' if start date is after the last study day.  
• End relative to treatment: Assign to 'BEFORE' if end date is prior to study 
treatment start date or if subject has not taken any study treatment. Else assign to 
'DURING' if start date falls into the on-treatment period or if subject is ongoing 
(not all study treatment discontinuation records completed) or (end date is missing 
and start relative to treatment not 'AFTER'). Else assign to 'AFTER' if start date is 
after the last study day or (end date is missing and start relative to 
treatment='AFTER'). 
 
Only on-treatment blood and blood supportive care and stem cell mobilization products 
that start after the start of study treatment are included in the Blood Products and Blood 
Supportive Care Product and Stem Cell Mobilization Products summaries. Therefore, for 
summary tables, include blood and blood supportive care product records where start 
relative to treatment in ('DURING') and end relative to treatment in ('DURING', 
'AFTER'). All data will be reported in listings. 


 
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Concomitant medication starts relative to treatment and ends relative to treatment flags 
are used to select data to include in the Concomitant Medication summaries as follows: 
 
• Summary of Concomitant Medications: This summary will contain medications 
including those with start date prior to study treatment start date and continue 
(missing end date or end date after study treatment start date) on therapy. Note that 
any medications with start date and end date prior to study treatment start date will be 
excluded. In addition, any medication that was started during post-therapy will be 
excluded. Include concomitant medication records where start relative to treatment in 
('BEFORE', 'DURING') and end relative to treatment in ('DURING', 'AFTER'). 
 


 
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14.4.2. 
Treatment Emergent Flag for Adverse Events 
Flag 
Definition 
Treatment 
Emergent 
• 
Study Treatment Start Date <= AE Start Date <= Start of Anti-cancer Therapy  
• 
AE Start Date is missing. 
 
NOTES:  
• 
Time of study treatment dosing and start/stop time of AEs should be considered, if collected. 
 


 
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14.5. 
Appendix 5: Data Display Standards & Handling 
Conventions 
14.5.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software will be used. 
Reporting Area 
HARP Server 
: US1SALX00259 
HARP Compound 
: arprod\gsk2857916\mid207504 
Analysis Datasets  
• 
Analysis datasets are “analysis-ready” datasets, i.e., analysis datasets that have a structure and 
content that allows statistical analysis to be performed with minimal programming, as sorting of the 
observations or the selection of the appropriate records from the analysis dataset. No complex data 
manipulations such as transformations or transpositions are required to perform the supported 
analysis. Analysis datasets will be created according to CDISC standards using ADaM IG 1.1 
specifications (where available) following PMDA-specific CDISC requirements wherever applicable, 
and data will be listed and summarised according to GSK Integrated Data Standards Library (IDSL) 
reporting standards. Formatting for dates, times, and decimal places will follow GSK standards 
except where specified. 
 
Generation of RTF Files 
• 
RTF files will be generated for all tables. 
14.5.2. 
Reporting Standards 
General 
• 
The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location: 
https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx): 
• 
4.03 to 4.23: General Principles 
• 
5.01 to 5.08: Principles Related to Data Listings 
• 
6.01 to 6.11: Principles Related to Summary Tables 
• 
7.01 to 7.13: Principles Related to Graphics  
• 
Do not include subject level listings in the main body of the GSK Clinical Study Report. All subject 
level listings should be located in the modular appendices as ICH or non-ICH listings 
Formats 
• 
GSK IDSL Statistical Principles (5.03 & 6.06.3) for decimal places (DP’s) will be adopted for 
reporting of data based on the raw data collected, unless otherwise stated. 
• 
Numeric data will be reported at the precision collected on the eCRF. 
• 
The reported precision from non eCRF sources will follow the IDSL statistical principles but may be 
adjusted to a clinically interpretable number of DP’s.  
Planned and Actual Time 
• 
Reporting for tables, figures, and formal statistical analyses: 
• 
Planned time relative to dosing will be used in figures, summaries, statistical analyses and 
calculation of any derived parameters, unless otherwise stated. 
• 
The impact of any major deviation from the planned assessment times and/or scheduled visit 
days on the analyses and interpretation of the results will be assessed as appropriate. 


 
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• 
Reporting for Data Listings:  
• 
Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1). 
• 
Unscheduled or unplanned readings will be presented within the subject’s listings.  
Unscheduled Visits 
• 
Unscheduled visits will not be included in summary tables and/or figures. For by planned time 
analysis, unscheduled visits will not be included. For worst-case analysis, unscheduled visits will be 
included 
• 
All unscheduled visits will be included in listings. 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• 
Refer to IDSL Statistical Principals 7.01 to 7.13. 
14.5.3. 
Reporting Standards for Pharmacokinetic 
Pharmacokinetic Concentration Data 
PC Windows Non-
Linear (WNL) File 
PC WNL file (CSV format) for the non-compartmental analysis by Clinical 
Pharmacology Modelling and Simulation function will be created according to 
SOP_00000314000: Non-Compartmental Analysis of Clinical Pharmacokinetic Data 
Note: Concentration values will be imputed as per GUI_51487 
Descriptive Summary 
Statistics, Graphical 
Displays and Listings 
Refer to IDSL PK Display Standards. 
Refer to IDSL Statistical Principle 6.06.1. 
Note: Concentration values will be imputed as per GUI_51487 for descriptive 
summary statistics/analysis and summarised graphical displays only.  
 
 
 
 
Pharmacokinetic Parameter Derivation 
PK Parameter to be 
Derived by 
Programmer 
The following PK parameters will be derived by the Programmer:  
• 
Ceoi and Ctrough 
• 
Accumulation ratios based on Cycles 1, 3, 6, 9 and 12 for Ceoi and Cycles 1, 
2, 5, 8, and 11 for Ctrough  
Pharmacokinetic Parameter Data 
Is NQ impacted PK 
Parameters Rule 
Being Followed 
Yes, refer to Standards for Handling NQ Impacted PK Parameters. 
NR at pre-dose 
NR (No Report) at pre-dose will be imputed as 0 for PK parameter derivation 
(GSK2857916 (ADC, Total Antibody)). 
Descriptive Summary 
Statistics, Graphical 
Displays and Listings 
Refer to IDSL PK Display Standards. 
 
 
 


 
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14.5.4. 
Reporting Standards for Pharmacodynamic 
Pharmacodynamic Parameter Data 
NQ 
NQ values for both 
 and complexed 
 will be imputed as each LLQ 
value. 
 
 
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14.6. 
Appendix 6: Derived and Transformed Data 
14.6.1. 
General 
Multiple Measurements at One Analysis Time Point 
• 
Mean of the measurements will be calculated and used in any derivation of summary statistics but if 
listed, all data will be presented. 
• 
Participants having both High and Low values for Normal Ranges at any post-baseline visit for 
safety parameters will be counted in both the High and Low categories of “Any visit post-baseline” 
row of related summary tables. This will also be applicable to relevant Potential Clinical Importance 
summary tables. 
Study Day 
• 
Calculated as the number of days from First Dose Date: 
• 
Ref Date = Missing      → Study Day = Missing  
• 
Ref Date < First Dose Date → Study Day = Ref Date – First Dose Date 
• 
Ref Data ≥ First Dose Date → Study Day = Ref Date – (First Dose Date) + 1     
 
14.6.2. 
Study Population 
Extent of Exposure 
• 
Number of days of exposure to study drug will be calculated based on the formula:   
Duration of Exposure in Days = min(Last Dose Date+20, Death date) – First Dose Date + 1 
• 
Participants who were randomized but did not report a treatment start date will be categorised as 
having zero days of exposure.  
• 
The cumulative dose will be based on the formula: 
Cumulative Dose (mg/kg) = Sum of Dose at Each Cycle 
• 
Dose intensity will be calculated based on the formula: 
Dose intensity (mg/kg/3 week) = Cumulative Dose/((Last Dose date – First Dose date +21)/21). 
14.6.3. 
Safety 
DLT 
DLT 
See Protocol Section 4.1.1. 
 
Adverse Events 
AE’S of Special Interest 
• 
Thrombocytopenia 
• 
Infusion-Related Reactions 
• 
Corneal events 
 
Ocular Exams 
Most frequent 
• 
The category that presents at the greatest number among all post-baseline visits will be designated 
as the most frequent. The worst category is chosen if more than one category is the mode.  
Best corrected visual acuity (BCVA) score 
• 
Partial BCVA score with trailing letter “p” is transformed to numeric value by removing the letter “p”. 


 
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14.7. 
Appendix 7: Reporting Standards for Missing Data 
14.7.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• 
Subject study completion (i.e. as specified in the protocol) was defined as ”A participant 
will be considered to have completed the study if he or she has received at least one 
dose of the study treatment and, has died or is still in follow-up when the study is 
closed, and has not withdrawn consent from study participation.”.  
• 
Participants who have been withdrawn from the study for reasons other than toxicity but 
prior to completion of DLT observation period will be replaced. 
• 
All available data from participants who were withdrawn from the study will be listed and 
all available planned data will be included in summary tables and figures, unless 
otherwise specified.  
14.7.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• 
Missing data occurs when any requested data is not provided, leading to blank fields on 
the collection instrument: 
o These data will be indicated using a “blank” in subject listing displays. Unless all 
data for a specific visit are missing in which case the data is excluded from the 
table.  
o Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such. 
Outliers 
• 
Any participants excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report. 
Responder 
Analysis 
• 
For endpoints which determine the percentage of responders, subjects with 
unknown/not evaluable or missing response will be assumed to be non-responders and 
will be included in the denominator when calculating the percentages. 
14.7.2.1. 
Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in subject listing displays. 
• 
Imputed partial dates will not be used to derive study day, duration (e.g. duration of 
adverse events), or elapsed time variables. In addition, imputed dates are not used for 
deriving the last contact date in the overall survival analysis dataset. 
• 
Imputed dates will not be displayed in listings. However, where necessary, display 
macros may impute dates as temporary variables for the purpose of sorting data in 
listings only. In addition, partial dates may be imputed for ‘slotting’ data to study time 
Adverse 
Events 
• 
The eCRF allows for the possibility of partial dates (i.e. only month and year) to be 
recorded for AE start and end dates; that is, the day of the month may be missing. In 
such a case, the following conventions will be applied for calculating the time to onset 
and the duration of the event: 
o Missing Start Day: First of the month will be used unless this is before the start 
date of study treatment; in this case the study treatment start date will be used and 
hence the event is considered On-treatment as per Appendix 4: Study Phases and 
Treatment Emergent Adverse Events. 


 
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Element 
Reporting Detail 
o Missing Stop Day: Last day of the month will be used, unless this is after the stop 
date of study treatment; in this case the study treatment stop date will be used. 
• 
Completely missing start or end dates will remain missing, with no imputation applied. 
Consequently, time to onset and duration of such events will be missing. 
• 
Completely or partially missing end dates will remain missing, with no imputation 
applied. Consequently, duration of such events will be missing 
Concomitant 
Medications/ 
Disease 
Characteristics 
• 
Partial dates for any concomitant medications recorded in the CRF will be imputed 
using the following convention: 
o If the partial date is a start date, a '01' will be used for the day and 'Jan' will be 
used for the month. 
o If the partial date is a stop date, a '28/29/30/31' will be used for the day (dependent 
on the month and year) and 'Dec' will be used for the month. 
• 
The recorded partial date will be displayed in listings. 
 


 
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14.8. 
Appendix 8: Values of Potential Clinical Importance 
14.8.1. 
Laboratory Values 
Reference ranges for all laboratory parameters collected throughout the study are 
provided by the laboratory. A laboratory value that is outside the reference range is 
considered either high abnormal (value above the upper limit of the reference range) or 
low abnormal (value below the lower limit of the reference range). Note: a high abnormal 
or low abnormal laboratory value is not necessarily of clinical concern. The laboratory 
reference ranges will be provided on the listings of laboratory data. Clinical laboratory 
test results outside of the reference range will be flagged in the listings. 
 
To identify laboratory values of potential clinical importance, National Cancer Institute 
Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03) will be used to 
assign grades to the relevant laboratory parameters. NCI-CTCAE v4.03 can be found at 
http://ctep.cancer.gov/reporting/ctc.html. 
 
For laboratory data which are not listed in the NCI CTCAE v4.03, a summary of values 
outside the normal range will be provided. 
14.8.2. 
ECG 
For ECG, the most updated IDSL standard up to the RAP effective date will be followed. 
14.8.3. 
Vital Signs 
For vital signs, the most updated IDSL standard up to the RAP effective date will be 
followed. 
 


 
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14.9. 
Appendix 9: Abbreviations & Trademarks 
14.9.1. 
Abbreviations 
Abbreviation 
Description 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
BOR 
Best Overall Response 
CDISC 
Clinical Data Interchange Standards Consortium 
CPMS 
Clinical Pharmacology Modelling & Simulation 
CR 
Complete Response 
DBF 
Database Freeze 
DP 
Decimal Places 
eCRF 
Electronic Case Record Form 
EOT 
End of Treatment 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Clinical Results Disclosure Requirements 
GSK 
GlaxoSmithKline 
ICH 
International Conference on Harmonization 
IDSL 
Integrated Data Standards Library 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PopPK 
Population PK 
PR 
Partial Response 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
QTcB 
Bazett’s QT Interval Corrected for Heart Rate 
RAP 
Reporting & Analysis Plan 
SAC 
Statistical Analysis Complete 
sCR 
Stringent Complete Response 
SDSP 
Study Data Standardization Plan 
SOP 
Standard Operation Procedure 
vGPR 
Very Good Partial Response 
14.9.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
None 
 
WinNonlin 
 
 
SAS 
 
 


 
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14.10. 
Appendix 10: List of Data Displays 
14.10.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.1 to 1.35 
1.1 to 1.1 
Efficacy 
2.1 to 2.1 
- 
Safety 
3.1 to 3.111 
3.1 to 3.3 
Pharmacokinetic 
4.1 to 4.12 
4.1 to 4.33 
Population Pharmacokinetic (PopPK) 
- 
- 
Pharmacodynamic and / or Biomarker 
6.1 to 6.6 
6.1 to 6.12 
Pharmacokinetic / Pharmacodynamic 
- 
7.1 to 7.12 
Section 
Listings 
ICH Listings 
1 to 54 
Other Listings 
55 to 79 
 
14.10.2. 
Mock Example Shell Referencing 
Non IDSL specifications will be referenced as indicated and if required example mock-up 
displays provided in a separate document detailing each mock shell for each display. 
Section 
Figure 
Table 
Listing 
Study Population 
POP_Fn 
POP_Tn 
POP_Ln 
Efficacy 
EFF_Fn 
EFF_Tn 
EFF_Ln 
Safety 
SAFE_Fn 
SAFE_Tn 
SAFE_Ln 
Pharmacokinetic 
PK_Fn 
PK_Tn 
PK_Ln 
Population Pharmacokinetic (PopPK) 
POPPK_Fn 
POPPK_Tn 
POPPK_Ln 
Pharmacodynamic and / or Biomarker 
PD_Fn 
PD_Tn 
PD_Ln 
Pharmacokinetic / Pharmacodynamic 
PKPD_Fn 
PKPD_Tn 
PK/PD_Ln 
NOTES:  
• 
Non-Standard displays are indicated in the ‘IDSL / Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’ 
 
14.10.3. 
Deliverables 
Delivery  
Description 
SAC 
Statistical Analysis Complete (Part 1) 
 


 
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14.10.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable  
Subject Disposition 
1.1. 
All Treated 
ES8 
Summary of Subject Status and Reason for Study Withdrawal 
(Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
1.2. 
All Treated 
SD4 
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
1.3. 
All Screened 
ES6 
Summary of Screening Status and Reasons for Screen Failure 
(Part 1) 
 
SAC 
Protocol Deviation 
1.4. 
All Treated 
DV1 
Summary of Important Protocol Deviations (Part 1) 
Only include ‘Any important protocol 
deviation’ 
Summarize: by ascending dose 
level, Total 
SAC 
1.5. 
All Treated 
IE1 
Summary of Inclusion/Exclusion Criteria Deviations (Part 1) 
Summarize: by ascending dose 
level, Total  
SAC 
Population Analysed 
1.6. 
All Screened 
SP1 
Summary of Study Populations (Part 1) 
All screened, All treated, DLT 
evaluable population, PK 
population, PD population 
SAC 
1.7. 
All Screened 
SP2A  
Summary of Exclusions from the Analysis Population (Part 1) 
IDSL  
Summarize: by ascending dose 
level, Total  
SAC 
Demographic and Baseline Characteristics 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable  
1.8. 
All Treated 
DM1 
Summary of Demographic Characteristics (Part 1) 
ICH E3, FDAAA, EudraCT 
Summarize age ranges as <18, 18 
to <65, 65 to <75, >=75 
Summarize: by ascending dose 
level, Total 
SAC 
1.9. 
All Treated 
DM5 
Summary of Race and Racial Combinations (Part 1) 
ICH E3, FDA, FDAAA, EudraCT 
Summarize: by ascending dose 
level, Total 
SAC 
1.10. 
All Treated 
DM11 
Summary of Age Ranges (Part 1) 
EudraCT 
Summarize: by ascending dose 
level, Total 
SAC 
1.11. 
All Treated 
DC1 
Summary of Disease Characteristics at Initial Diagnosis (Part 1) 
Summarize: by ascending dose 
level, Total 
Summarize time since initial 
diagnosis in years and stage at 
initial diagnosis  
SAC 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable  
1.12. 
All Treated 
DC2 
Summary of Disease Characteristics at Screening (Part 1) 
Summarize: by ascending dose 
level, Total.  Summarize stage, 
lines of therapy completed at 
screening (1-10 lines, More than 10 
lines, Missing), Type of multiple 
myeloma (Nonsecretory, Secretory, 
Missing), Myeloma Light chain 
(Kappa Light Chain, Lambda Light 
Chain, Missing), Myeloma 
immunoglobulin (IgA, IgD, IgE, IgG, 
IgM Other, Missing), Extramedullary 
Disease, Lytic bone lesions 
SAC 
Prior and Concomitant Medications 
1.13. 
All Treated 
MH1 
Summary of Past Medical Conditions (Part 1) 
ICH E3  
Summarize: by ascending dose 
level, Total 
SAC 
1.14. 
All Treated 
MH1 
Summary of Current Medical Conditions (Part 1) 
ICH E3  
Summarize: by ascending dose 
level, Total 
SAC 
1.15. 
All Treated 
MH1 
Summary of Genetic Characteristics and Cytogenetic Risk (Part 
1) 
ICH E3  
Summarize: by ascending dose 
level, Total 
SAC 
1.16. 
All Treated 
CM8 
Summary of Concomitant Medications (Part 1) 
ICH E3 
Summarize: by ascending dose 
level, Total 
SAC 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable  
1.17. 
All Treated 
CM1 
Summary of Prophylactic Medication for Infusion-Related 
Reactions by Drug Class and Drug Name (Part 1) 
Medication will be identified based 
on verbatim term, and the drug 
class will be based on the 
medication group in the excel file 
provided by Clinical. Summarize: by 
ascending dose level, Total 
SAC 
1.18. 
All Treated 
CM1 
Summary of Eye Medications by Drug Class and Drug Name 
(Part 1) 
Medication will be identified based 
on verbatim term, and the drug 
class will be based on the 
medication group in the excel file 
provided by Clinical. Summarize: by 
ascending dose level, Total 
SAC 
1.19. 
All Treated 
[Non-Standard] 
POP_T1 
Summary of Percentage of Duration of Exposure on Steroid Eye 
Drop Use (Part 1) 
See 205678 RAP T1.0170 (Mock-
up POP_T1) (“Prophylactic eye 
drops” will be ticked in the CM 
dataset and ATC4 will be identified 
as S01BA). 
SAC 
1.20. 
All Treated 
BP1A 
Summary of Blood Products on Treatment (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
1.21. 
All Treated 
BP1C 
Summary of Blood Supportive Care Products on Treatment (Part 
1) 
Summarize: by ascending dose 
level, Total 
SAC 
1.22. 
All Treated 
BP1A 
Summary of Prior Stem Cell Transplant (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
Anti-Cancer Therapies 
1.23. 
All Treated 
[Non-Standard] 
POP_T2 
Summary of Prior Anti-Cancer Therapy by Drug Class of Agents 
(Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable  
1.24. 
All Treated 
CM8 
Summary of Prior Dictionary Coded Anti-Cancer Therapy (Part 
1) 
Summarize: by ascending dose 
level, Total 
SAC 
1.25. 
All Treated 
AC3 
Summary of Number of Prior Anti-Cancer Therapy Regimens 
(Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
1.26. 
All Treated 
RE1A 
Summary of Best Response to Most Recent Prior Anti-Cancer 
Therapy (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
1.27. 
All Treated 
[Non-Standard] 
POP_T2 
Summary of Follow-up Anti-Cancer Therapy by Drug Class of 
Agents (Part 1) 
Summarize: by ascending dose 
level, Total  
SAC 
1.28. 
All Treated 
CM8 
Summary of Follow-up Dictionary Coded Anti-Cancer Therapy 
(Part 1) 
Summarize: by ascending dose 
level, Total  
SAC 
1.29. 
All Treated 
OSP2 
Summary of Prior Cancer and Non-Cancer Related Surgical 
Procedure (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
Exposure and Treatment Modification 
1.30. 
All Treated 
OEX5 
Summary of Exposure (Part 1) 
Summarize: by ascending dose 
level, Total 
# of cycles; Cumulative actual dose 
(mg/kg): sum of dose at each cycle; 
dose intensity per cycle 
(mg/kg/cycle);dose intensity 
(mg/kg/3 weeks) = cumulative 
actual dose / (Last Dose date – First 
Dose date + 21)/21) 
SAC 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example Shell Title  
Programming Notes 
Deliverable  
1.31. 
All Treated 
OEX6 
Summary of Actual Dose Delivered by Cycle (Part 1) 
Actual dose delivered by cycle 
(mg/kg/cycle) summarised by 
ascending dose level, no Total 
needed, and by each cycle 
SAC 
1.32. 
All Treated 
ODMOD1 
Summary of Dose Reductions (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
1.33. 
All Treated 
ODMOD3 
Summary of Duration of Delay and Time to First Dose Delay 
(Part 1) 
Summarize: by ascending dose 
level, Total 
Duration of delays = (actual start 
date of current dose - expected start 
date of dose). Expected start date 
of dose = actual start date of 
previous dose + 21 
Duration of delays: 1-21 days, 22-
42 days, >42 days 
First delay: first dose delay or first 
dose restarted after skipped dosing 
SAC 
1.34. 
All Treated 
ODMOD8 
Summary of Incomplete Infusions (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
1.35. 
All Treated 
ODMOD9 
Summary of Infusion Interruptions (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
 


 
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14.10.5. 
Study Population Figures 
Study Population: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Exposure and Treatment Modification 
1.1 
All Treated 
OEX12 
Swimmer Plot of Duration Treatment (Part 1) 
Occurrences of onset PR, VGPR, 
CR, sCR, PD, and Study status 
SAC 
14.10.6. 
Efficacy Tables 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Overall Response Rate (ORR) and Clinical Benefit Rate (CBR) 
2.1.  
All Treated 
RE1A 
Summary of Overall Response and Clinical Benefit Rate (With 
Confirmation) per IMWG Response Criteria by Dose Level (Part 
1) 
Summarize: by ascending dose 
level, Total 
Unknown or missing response will 
be treated as no response, i.e. such 
subjects will be included in the 
denominator when calculating the 
rates 
Response confirmation algorithm is 
in Table 5 
Best Response will be summarised. 
ORR and CBR will be summarised 
with 95% CI. 
SAC 
 


 
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14.10.7. 
Safety Tables 
Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Dose Limiting Toxicity (DLT) 
3.1.  
All Treated 
AE19 
Summary of Dose-Limiting Toxicities during the 
Determinative Period (Part 1) 
Summarize: by ascending dose 
level, Total 
Add a footnote “The determinative 
period is the first 21 days of 
intervention” 
SAC 
Adverse Events (AEs) 
3.2.  
All Treated 
AE13 
Adverse Event Overview (Part 1) 
Summarize: by ascending dose 
level, Total 
Include # and % of pts with any 
AE, related AE, Grade 3/4, Grade 
3/4 related, dose reduction, dose 
delays, incomplete infusions, 
infusion interruptions, trt discon’t, 
SAE, related SAE, fatal, related 
fatal 
SAC 
3.3.  
All Treated 
AE15 
Summary of Common (>=2 subjects) Non-serious Adverse 
Events by System Organ Class and Preferred Term (Number 
of Participant and Occurrences) (Part 1) 
FDAAA, EudraCT 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.4.  
All Treated 
OAE07 
Summary of All Adverse Events by Preferred Term and 
Maximum Grade (Part 1) 
Summarize: by ascending dose 
level, Total 
Preferred term row: A subject with 
the same term multiple grades will 
be counted once with the 
maximum grade. 
Any event row: each subject with 
at least one AE will be counted 
only once at the maximum grade 
Similar to T3.0030 in BMA117159 
SAC 
3.5.  
All Treated 
OAE01 
Summary of All Adverse Events by System Organ Class, 
Preferred Term, and Maximum Grade (Part 1) 
Summarize: by ascending dose 
level, Total 
Preferred term row: A subject with 
the same term multiple grades will 
be counted once with the 
maximum grade. 
Any event row: each subject with 
at least one AE will be counted 
only once at the maximum grade 
See T3.0030 in BMA117159 
SAC 
3.6.  
All Treated 
OAE01 
Summary of Study Treatment-related Adverse Events by 
System Organ Class, Preferred Term, and Maximum Grade 
(Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.7.  
All Treated 
AE3 
Summary of Non-Serious Study Treatment-Related Adverse 
Events by Overall Frequency (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.8.  
All Treated 
DTH1A 
Summary of Deaths (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.9.  
All Treated 
AE3 
Summary of Adverse Events by Preferred Term (Part 1) 
 
SAC 
3.10. 
 
All Treated 
AE3 
Summary of Adverse Events Leading to Permanent 
Discontinuation of GSK2857916 by Preferred Term (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.11. 
 
All Treated 
AE3 
Summary of Adverse Events Leading to Dose Reduction of 
GSK2857916 by Preferred Term (Part 1) 
 
SAC 
3.12. 
 
All Treated 
AE3 
Summary of Adverse Events Leading to Dose Delay of 
GSK2857916 by Preferred Term (Part 1) 
 
SAC 
3.13. 
 
All Treated 
OAE07 
Summary of Treatment Emergent Adverse Events by 
Preferred Term and Maximum Grade (Part 1) 
 
SAC 
Serious and Other Significant Adverse Events 
3.14. 
 
All Treated 
AE16 
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of Subjects and Occurrences) 
(Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.15. 
 
All Treated 
AE3 
Summary Study Treatment-related Serious Adverse Events in 
Descending Order of Total Incidence by Preferred Term (Part 
1) 
 
SAC 
AEs of Special Interest 
3.16. 
 
All Treated 
OAE01 
Summary of All Corneal Events (CTCAE) by Maximum Grade 
Events in Descending Order of Total Incidence by System 
Organ Class and Preferred Term (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.17. 
 
All Treated 
ESI1 
Summary of Characteristics of Corneal Events (CTCAE) (Part 
1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.18. 
 
All Treated 
ESI1 
Summary of Characteristics of Corneal Events (GSK Scale) 
(Part 1) 
Summarize: by ascending dose 
level, Total 
Use information in Ocular grading 
form 
SAC 
3.19. 
 
All Treated 
ESI2B 
Summary of Onset and Duration of the First Occurrence of 
Corneal Events (CTCAE) (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.20. 
 
All Treated 
ESI2B 
Summary of Onset and Duration of the First Occurrence of 
Corneal Events (GSK scale) of Grade 2 or Above (Part 1) 
Summarize: by ascending dose 
level, Total 
Use information in Ocular grading 
form 
SAC 
3.21. 
 
All Treated 
AE3 
Summary of Corneal Events Leading to Permanent 
Discontinuation of GSK2857916 (CTCAE) (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.22. 
 
All Treated 
AE3 
Summary of Corneal Events Leading to Dose Reductions 
(CTCAE) (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.23. 
 
All Treated 
AE3 
Summary of Corneal Events Leading to Dose Delays 
(CTCAE) (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.24. 
 
All Treated 
OAE07 
Summary of Thrombocytopenia by Maximum Grade Events in 
Descending Order of Total Incidence by Preferred Term (Part 
1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.25. 
 
All Treated 
ESI1 
Summary of Characteristics of Thrombocytopenia (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.26. 
 
All Treated 
ESI2B 
Summary of Onset and Duration of the First Occurrence of 
Thrombocytopenia (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.27. 
 
All Treated 
OAE07 
Summary of Infusion-Related Reactions by Maximum Grade 
Events in Descending Order of Total Incidence by Preferred 
Term (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.28. 
 
All Treated 
ESI1 
Summary of Characteristics of Infusion-Related Reactions 
(Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.29. 
 
All Treated 
ESI2B 
Summary of Onset and Duration of the First Occurrence of 
Infusion-Related Reactions (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
Laboratory: Chemistry 
3.30. 
 
All Treated 
LB1 
Summary of Chemistry Changes from Baseline (Part 1) 
ICH E3 
Summarize: by ascending dose 
level, Total 
SAC 
3.31. 
 
All Treated 
LB1 
Summary of Chemistry at Scheduled Visits (Part 1) 
ICH E3 
Summarize: by ascending dose 
level, Total 
SAC 
3.32. 
 
All Treated 
OLB9A 
Summary of Chemistry Worst Case Grade Change from 
Baseline (Part 1) 
Summarize: by ascending dose 
level, Total 
For lab tests that are graded by 
CTCAE v4.03;  
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.33. 
 
All Treated 
OLB11A 
Summary of Chemistry Worst Case Changes from Baseline 
with Respect to the Normal Range (Part 1) 
Summarize: by ascending dose 
level, Total 
Decreases to low, changes to 
normal or no changes from 
baseline, and increases to high will 
be summarised for the worst case 
post-baseline. If a subject has a 
decrease to low and an increase to 
high during the same time interval, 
then the subject is counted in both 
the “Decrease to Low” categories 
and the “Increase to High” 
categories. 
SAC 
Laboratory: Hematology 
3.34. 
 
All Treated 
LB1 
Summary of Hematology Changes from Baseline (Part 1) 
ICH E3 
Summarize: by ascending dose 
level, Total 
SAC 
3.35. 
 
All Treated 
LB1 
Summary of Hematology at Scheduled Visits (Part 1) 
ICH E3 
Summarize: by ascending dose 
level, Total 
SAC 
3.36. 
 
All Treated 
OLB9A 
Summary of Hematology Worst Case Grade Change from 
Baseline (Part 1) 
For lab tests that are graded by 
CTCAE v4.03;  
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.37. 
 
All Treated 
OLB11A 
Summary of Hematology Worst Case Changes from Baseline 
with Respect to the Normal Range (Part 1) 
Summarize: by ascending dose 
level, Total 
For lab tests that are not gradable 
by CTCAE v4.03. 
Decreases to low, changes to 
normal or no changes from 
baseline, and increases to high will 
be summarised for the worst case 
post-baseline. If a subject has a 
decrease to low and an increase to 
high during the same time interval, 
then the subject is counted in both 
the “Decrease to Low” categories 
and the “Increase to High” 
categories. 
SAC 
Laboratory: Disease Evaluation 
3.38. 
 
All Treated 
LB1 
Summary of Disease Evaluation Changes from Baseline (Part 
1) 
ICH E3 
Summarize: by ascending dose 
level, Total 
Include: CACRALB, IGA, IGD, 
IGE, IGG, IGM, KLCLLC, 
KAPPALC, LMBDLC, MCPROT, 
MCPROTZ, MCPRT24Z 
(ELECTROPHORESIS), 
MCPRT24Z (IMMUNOFIXATI ON 
ELECTROPHORESIS) 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.39. 
 
All Treated 
OLB11A 
Summary of Disease Evaluation Worst Case Changes from 
Baseline with Respect to the Normal Range (Part 1) 
Summarize: by ascending dose 
level, Total 
Decreases to low, changes to 
normal or no changes from 
baseline, and increases to high will 
be summarised for the worst case 
post-baseline. If a subject has a 
decrease to low and an increase to 
high during the same time interval, 
then the subject is counted in both 
the “Decrease to Low” categories 
and the “Increase to High” 
categories. 
SAC 
Laboratory: Urinalysis 
3.40. 
  All Treated 
LB1 
Summary of Urine Concentration Changes from Baseline 
(Part 1) 
ICH E3 
Summarize: by ascending dose 
level, Total 
SAC 
3.41. 
  All Treated 
LB1 
Summary of Urine Concentration at Scheduled Visits (Part 1) 
ICH E3 
Summarize: by ascending dose 
level, Total 
SAC 
3.42. 
 
All Treated 
UR1 
Summary of the Worst Case Urinalysis Results (Discrete or 
Character Values) Post-Baseline Relative to Baseline (Part 1) 
ICH E3 
Summarize: by ascending dose 
level, Total 
SAC 
Laboratory: Hepatobiliary (Liver) 
3.43. 
  All Treated 
LIVER1 
Summary of Liver Monitoring/Stopping Event Reporting (Part 
1) 
Summarize: by ascending dose 
level, Total 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.44. 
 
All Treated 
LIVER10 
Summary Hepatobiliary Laboratory Abnormalities Including 
Possible Hy’s Law Case (Part 1) 
Summarize: by ascending dose 
level, Total 
Possible Hy’s law cases are 
defined as any elevated 
ALT≥3×ULN, total bilirubin≥2×ULN 
and ALP<2×ULN/missing. Total 
bilirubin≥2×ULN can be within 28 
days following the ALT elevation 
and if direct bilirubin is available on 
the same day, it must be ≥ 35% of 
total bilirubin. ALP<2xULN/missing 
means the criteria is satisfied 
unless the ALP is ≥2xULN at any 
time of bilirubin elevation within the 
28 day window 
SAC 
Laboratory: Others 
3.45. 
 
All Treated 
LB1 
Summary of eGFR Changes from Baseline (Part 1) 
ICH E3 
Summarize: by ascending dose 
level, Total 
SAC 
3.46. 
 
All Treated 
LB1 
Summary of eGFR at Scheduled Visits (Part 1) 
ICH E3 
Summarize: by ascending dose 
level, Total 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.47. 
 
All Treated 
OLB11A 
Summary of eGFR Worst Case Changes from Baseline with 
Respect to the Normal Range (Part 1) 
Summarize: by ascending dose 
level, Total 
For lab tests that are not gradable 
by CTCAE v4.03. 
Decreases to low, changes to 
normal or no changes from 
baseline, and increases to high will 
be summarised for the worst case 
post-baseline. If a subject has a 
decrease to low and an increase to 
high during the same time interval, 
then the subject is counted in both 
the “Decrease to Low” categories 
and the “Increase to High” 
categories. 
SAC 
Performance Status 
3.48. 
 
All Treated 
PS1A 
Summary of ECOG Performance Status at Baseline and 
Post-baseline Scheduled Visits (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.49. 
 
All Treated 
PS3A 
Summary of Change in ECOG Performance Status from 
Baseline by Scheduled Visits and the Worst and Best Case 
Post-Baseline Changes During Study (Part 1) 
Summarize: by ascending dose 
level, Total 
Categories are Improved, no 
change, deteriorated. 
 SAC 
ECG 
3.50. 
 
All Treated 
EG1 
Summary of ECG Findings (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.51. 
 
All Treated 
EG2 
Summary of Change from Baseline in ECG Values (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 


 
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No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.52. 
 
All Treated 
OECG1B 
Summary of Increases in QTcF (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.53. 
 
All Treated 
OECG2B 
Summary of Amount of Increase from Baseline Value in 
QTcF (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.54. 
 
All Treated 
OLVEF1A 
Summary of Left Ventricular Ejection Fraction Change from 
Baseline (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
Vital Signs and Body Weight 
3.55. 
 
All Treated 
VS1 
Summary of Vital Signs by Scheduled Visit (Part 1) 
ICH E3 
Includes Baseline values 
SAC 
3.56. 
 
All Treated 
VS1 
Summary of Change from Baseline in Vital Signs by 
Scheduled Visit (Part 1) 
ICH E3 
Includes Baseline values 
SAC 
3.57. 
 
All Treated 
OVT1B 
Summary of Worst Case Changes from Baseline in Heart 
Rate (Part 1) 
ICH E3 
SAC 
3.58. 
 
All Treated 
OVT2B 
Summary of Worst Case Increase from Baseline in Systolic 
Blood Pressure (Part 1) 
ICH E3 
SAC 
3.59. 
 
All Treated 
OVT2B 
Summary of Worst Case Increase from Baseline in Diastolic 
Blood Pressure (Part 1) 
ICH E3 
SAC 
3.60. 
 
All Treated 
OVT1B 
Summary of Worst Case Changes from Baseline in 
Temperature (Part 1) 
ICH E3 
SAC 
Anti-Drug Antibody 
3.61. 
 
All Treated 
[Non-Standard] 
SAFE_T1 
Summary of Human Anti-GSK2857916 Antibodies (ADA) 
Over Time (Part 1) 
 
SAC 
3.62. 
 
All Treated 
[Non-Standard] 
SAFE_T2 
Summary of Human Anti-GSK2857916 Antibodies (ADA) 
(Part 1) 
ICH E3 
Summarize overall at post-baseline 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Ocular findings during on-treatment period (from Baseline to End of Treatment) 
3.63. 
 
All Treated 
[Non-Standard] 
SAFE_T3 
Summary of Best Corrected Visual Acuity Test (BCVA) 
Scores (logMAR score) (Part 1) 
Summarize: by ascending dose 
level, Total 
Use table 3.0501 from BMA117159 
as template. Following “worst 
change from baseline’; add 
summary of change (category) for 
‘Most frequent change from 
baseline’.   
SAC 
3.64. 
 
All Treated 
[Non-Standard] 
SAFE_T3 
Summary of Best Corrected Visual Acuity Test (BCVA) 
Scores (logMAR score) due to Corneal Finding (Part 1) 
Summarize: by ascending dose 
level, Total 
Use table 3.0501 from BMA117159 
study as template. Following “worst 
change from baseline’; add 
summary of change (category) for 
‘Most frequent change from 
baseline’.   
SAC 
3.65. 
 
All Treated 
[Non-Standard] 
SAFE_T4 
Number (%) of Subjects with Intraocular Pressure (IOP) >= 
22mm Hg Anytime Post-baseline (Part 1) 
Summarize: by ascending dose 
level, Total 
SAC 
3.66. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Pupillary Exam Findings from Baseline to Worst Post-
Baseline (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (L/R) and 
subject (worse eye) 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.67. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Extraocular Muscle Movement from Baseline to Worst 
Post-Baseline (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (L/R) and 
subject (worse eye) 
SAC 
3.68. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Ptosis from Baseline to Worst Post-Baseline (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (L/R) and 
subject (worse eye) 
SAC 
3.69. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Blepharitis/MGD from Baseline to Worst Post-
Baseline (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (L/R) and 
subject (worse eye) 
SAC 
3.70. 
 
All Treated 
 
[Non-Standard] 
SAFE-T5 
Shift in Conjunctival Exam Findings for Chemosis from 
Baseline to Worst Post-Baseline (Part 1) 
Summarize: by ascending dose 
level, Total 
Create shift table for each of 3 
findings: Chemosis 
(Absent/Present); 
By eye (L/R) and subject (worse 
eye) 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.71. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Conjunctival Exam Findings for Bulbar and Palpebral 
Conjunctiva from Baseline to Worst Post-Baseline (Part 1) 
Summarize: by ascending dose 
level, Total 
Create shift table for each of 3 
findings: Bulbar Conjunctiva White 
and Quiet: (Yes/No); Palpebral 
Conjunctiva within normal limits 
(Yes/No); 
By eye (L/R) and subject (worse 
eye) 
SAC 
3.72. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Scleritis from Baseline to Worst Post-Baseline (Part 1) 
By eye (L/R) and subject (both 
eyes in same ocular exam) 
SAC 
3.73. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Corneal Epithelium Findings from Baseline to Worst 
Post-Baseline (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (L/R 
SAC 
3.74. 
 
All Treated 
[Non-Standard] 
SAFE_T6 
Summary of Findings for Punctate Keratopathy (Part 1) 
Summarize: by ascending dose 
level, Total, across ocular exams, 
and by eye (L/R).  
SAC 
3.75. 
 
All Treated 
[Non-Standard] 
SAFE_T6 
Summary for Findings Related to Microcystic Edema (Part 1) 
Summarize: by ascending dose 
level, Total, across ocular exams, 
and by eye (L/R).  
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.76. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Findings Related to Microcystic Edema from Baseline 
to Worst Post-Baseline (Part 1) 
 
SAC 
3.77. 
 
All Treated 
[Non-Standard] 
SAFE_T6 
Summary for Findings Related to Microcystic without Edema 
(Part 1) 
Summarize: by ascending dose 
level, Total, across ocular exams, 
and by eye (L/R).  
SAC 
3.78. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Findings Related to Microcystic without Edema from 
Baseline to Worst Post-Baseline (Part 1) 
 
SAC 
3.79. 
 
All Treated 
[Non-Standard] 
SAFE_T6 
Summary for Findings Related to Subepithelial Haze (Part 1) 
Summarize: by ascending dose 
level, Total, across ocular exams, 
and by eye (L/R).  
SAC 
3.80. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Findings Related to Subepithelial Haze from Baseline 
to Worst Post-Baseline (Part 1) 
 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.81. 
 
All Treated 
[Non-Standard] 
SAFE_T6 
Summary for Findings Related to Corneal Neovascularization 
(Part 1) 
Summarize: by ascending dose 
level, Total, across ocular exams, 
and by eye (L/R).  
SAC 
3.82. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Findings Related to Corneal Neovascularization from 
Baseline to Worst Post-Baseline (Part 1) 
 
SAC 
3.83. 
 
All Treated 
[Non-Standard] 
SAFE_T6 
Summary for Findings Related to Stroma (Part 1) 
 
Summarize: by ascending dose 
level, Total, across ocular exams, 
and by eye (L/R). 
SAC 
3.84. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Findings Related to Stroma from Baseline to Worst 
Post-Baseline (Part 1) 
 
SAC 
3.85. 
 
All Treated 
[Non-Standard] 
SAFE_T6 
Summary for Findings Related to Active Opacity (Part 1) 
Summarize: by ascending dose 
level, Total, across ocular exams, 
and by eye (L/R). See section 
8.6.4 and mock shell document for 
details. 
SAC 


 
CONFIDENTIAL 
 
 
 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.86. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Findings Related to Active Opacity from Baseline to 
Worst Post-Baseline (Part 1) 
 
SAC 
3.87. 
 
All Treated 
[Non-Standard] 
SAFE_T6 
Summary for Findings Related to Active Edema (Part 1) 
Summarize: by ascending dose 
level, Total, across ocular exams, 
and by eye (L/R). See section 
8.6.4 and mock shell document for 
details. 
SAC 
3.88. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Findings Related to Active Edema from Baseline to 
Worst Post-Baseline (Part 1) 
 
SAC 
3.89. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Corneal Endothelium Findings from Baseline to Worst 
Post-Baseline (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (L/R).  
SAC 
3.90. 
 
All Treated 
[Non-Standard] 
SAFE_T4 
Summary for Descemet's Folds Findings (Part 1) 
Summarize: by ascending dose 
level, Total, 
Among eyes with Corneal 
endothelium = Abnormal in at least 
one post-baseline ocular exam. 
See section 8.6.4 and mock shell 
document for details. 
SAC 


 
CONFIDENTIAL 
 
 
 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.91. 
 
All Treated 
[Non-Standard] 
SAFE_T6 
Summary for Endothelial Lesion Findings (Part 1) 
Summarize: by ascending dose 
level, Total, across ocular exams, 
and by eye (L/R). See section 
8.6.4 and mock shell document for 
details. 
SAC 
3.92. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Slit Lamp Exam Findings from Baseline to Worst 
Post-Baseline (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (L/R). See 
section 8.6.4 and mock shell 
document for details. 
SAC 
3.93. 
 
All Treated 
[Non-Standard] 
SAFE_T4 
Number (%) of Eye with Iris Findings at Any Time Post-
Baseline (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (L/R). 
Summary tables for number (%) of 
eyes with 'Transillumination 
defect', 'Nodules', or 
'Neovascularization' at any post-
baseline ocular exam 
SAC 
3.94. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Cataracts from Baseline to Worst Post-Baseline (Part 
1) 
Summarize: by ascending dose 
level, Total, By eye (L/R). See 
section 8.6.4 and mock shell 
document for details. 
SAC 
3.95. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Summary of Grade Change in Cataract from Baseline to 
Post-Baseline (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (L/R). See 
section 8.6.4 and mock shell 
document for details. 
SAC 


 
CONFIDENTIAL 
 
 
 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.96. 
 
All Treated 
[Non-Standard] 
SAFE_T5 
Shift in Findings from FUNDUS Photograph from Baseline to 
Worst Post-Baseline (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (L/R). See 
section 8.6.4 and mock shell 
document for details. 
SAC 
Ocular findings during Follow-up period (from EOT to Last Follow-up Visit) 
3.97. 
 
All Treated 
[Non-Standard] 
SAFE_T3 
Summary of Change (Worsening, No Change, Improvement) 
in Best Corrected Visual Acuity (BCVA) from EOT Visit to 
Last Follow-Up Visit (Part 1) 
Summarize: by ascending dose 
level, Total 
See section 8.6.4 Ocular Exams 
and mock shell for details 
SAC 
3.98. 
 
All Treated 
[Non-Standard] 
SAFE_T3 
Summary of Change (Worsening, No Change, Improvement) 
in Intraocular Pressure (IOP) from EOT Visit to Last Follow-
Up Visit (Part 1) 
Summarize: by ascending dose 
level, Total 
See section 8.6.4 Ocular Exams 
and mock shell for details 
SAC 
3.99. 
 
All Treated 
[Non-Standard] 
SAFE_T6 
Summary of Change (Worsening, No Change, Improvement) 
in Corneal Epithelium Findings from EOT Visit to Last Follow-
Up Visit (Part 1) 
Summarize: by ascending dose 
level, Total 
See section 8.6.4 Ocular Exams 
and mock shell for details 
SAC 
3.100.  
All Treated 
[Non-Standard] 
SAFE_T6 
Summary of Change (Worsening, No Change, Improvement) 
in Corneal Endothelium Findings from EOT Visit to Last 
Follow-Up Visit (Part 1) 
Summarize: by ascending dose 
level, Total 
See section 8.6.4 Ocular Exams 
and mock shell for details 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.101.  
All Treated 
[Non-Standard] 
SAFE_T7 
Summary of Resolution Time from EOT in Best Corrected 
Visual Acuity (BCVA) (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (R/L). 
See section 8.6.4 Ocular Exams 
and mock shell for details 
SAC 
3.102.  
All Treated 
[Non-Standard] 
SAFE_T7 
Summary of Resolution Time from EOT in Intraocular 
Pressure (IOP) (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (R/L). 
See section 8.6.4 Ocular Exams 
and mock shell for details 
SAC 
3.103.  
All Treated 
[Non-Standard] 
SAFE_T7 
Summary of Resolution Time from EOT in Corneal Epithelium 
Findings (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (R/L).  
See section 8.6.4 and mock shell 
document for details 
SAC 
3.104.  
All Treated 
[Non-Standard] 
SAFE_T7 
Summary of Resolution Time from EOT in Corneal 
Endothelium (Part 1) 
Summarize: by ascending dose 
level, Total, By eye (R/L).  
See section 8.6.4 and mock shell 
document for details 
SAC 
COVID-19 
3.105.  
Screened 
PAN1 
Summary of COVID-19 Assessment for Subjects with 
COVID-19 Adverse Events (Part 1) 
 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.106.  
Screened 
PAN10A 
Summary of Exposure Adjusted Incidence Rates of Adverse 
Events Over Time (Part 1) 
 
SAC 
3.107.  
Screened 
PAN11 
Summary of Exposure Adjusted Incidence Rates for Common 
Adverse Events (Part 1) 
Include footnote: 
Note: Common adverse events 
include those occurring in >2 
subjects. 
SAC 
Additional Tables for Corneal Events 
3.108.  
All Treated 
[Non-Standard] 
SAFE_T8 
Summary of Corneal Events (GSK Scale) by Grade and Visit 
(Part 1) 
See Section 8.6.4 and mock shell 
document for details 
SAC 
3.109.  
All Treated 
AE13 
Corneal Event (GSK Scale) Overview (Part 1) 
See Section 8.6.4 and mock shell 
document for details 
SAC 
3.110.  
All Treated 
[Non-Standard] 
SAFE_T9 
Summary of Action Taken with Study Treatment for Corneal 
Events (GSK Scale) by Visit (Part 1) 
Summarize: by ascending dose 
level, Total.  
See Section 8.6.4 and mock shell 
document for details 
SAC 


 
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Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
3.111.  
All Treated 
AE13 
Corneal Event (CTCAE) Overview (Part 1) 
See Section 8.6.4 and mock shell 
document for details 
SAC 
 


 
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14.10.8. 
Safety Figures 
Safety: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Laboratory 
3.1.  
All Treated 
LB11 
Liver Function Tests Patient Profiles Plot for Subjects with 
ALT/AST/Total Bilirubin of Toxicity Grade 2 or Above (Part 1) 
 
SAC 
3.2.  
All Treated 
LIVER14 
Scatter Plot of Maximum vs. Baseline for ALT (Part 1) 
 
SAC 
3.3.  
All Treated 
LIVER9 
Scatter Plot of Maximum ALT vs. Maximum Total Bilirubin (Part 
1) 
 
SAC 
 
 


 
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14.10.9. 
Pharmacokinetic Tables 
Pharmacokinetic: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Drug Concentration Measure 
4.1.  
PK 
PK01 
Summary of Plasma GSK2857916 (ADC) PK Concentration-
Time Data (Part 1) 
By dose level 
SAC 
4.2.  
PK 
PK01 
Summary of Plasma GSK2857916 (Total Antibody) PK 
Concentration-Time Data (Part 1) 
By dose level 
SAC 
4.3.  
PK 
PK01 
Summary of Plasma cys-mcMMAF PK Concentration-Time 
Data (Part 1) 
By dose level 
SAC 
4.4.  
PK 
PK13 
Listing of Derived GSK2857916 (ADC) PK Parameters 
(Untransformed) (Part 1) 
 
SAC 
4.5.  
PK 
PK13 
Listing of Derived GSK2857916 (Total Antibody) PK 
Parameters (Untransformed) (Part 1) 
 
SAC 
4.6.  
PK 
PK13 
Listing of Derived cys-mcMMAF PK Parameters 
(Untransformed) (Part 1) 
 
SAC 
Pharmacokinetic Parameters 
4.7.  
PK 
PK06 
Summary of Derived GSK2857916 (ADC) PK Parameters (Part 
1) 
By dose level  
PK06 with both transformed and 
untransformed values.  
SAC 
4.8.  
PK 
PK06 
Summary of Derived GSK2857916 (Total Antibody) PK 
Parameters (Part 1) 
By dose level  
PK06 with both transformed and 
untransformed values.  
SAC 
4.9.  
PK 
PK06 
Summary of Derived cys-mcMMAF PK Parameter (Part 1) 
By dose level  
PK06 with both transformed and 
untransformed values. 
SAC 


 
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Pharmacokinetic: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Accumulation Ratio 
4.10. 
PK 
PK05 
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (ADC) (Part 1) 
By dose level  
Include R(Ctrough) and R(Ceoi) 
with 95%CI, SD log and %CVb in 
one table.  
SAC 
4.11. 
PK 
PK05 
Summary of Results of Accumulation Ratio Assessment for 
GSK2857916 (Total Antibody) (Part 1) 
By dose level  
Include R(Ctrough) and R(Ceoi) 
with 95%CI, SD log and %CVb in 
one table.  
SAC 
4.12. 
PK 
PK05 
Summary of Results of Accumulation Ratio Assessment for 
cys-mcMMAF (Part 1) 
By dose level  
Include R(Ctrough) and R(Ceoi) 
with 95%CI, SD log and %CVb in 
one table.  
SAC 


 
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14.10.10. Pharmacokinetic Figures 
Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Drug Concentration Measure 
4.1.  
PK 
PK17 
Individual Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) by Dose (Part 1) 
 
SAC 
4.2.  
PK 
PK17 
Individual Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 1) 
 
SAC 
4.3.  
PK 
PK17 
Individual Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) by Dose – Cycle 1 (Part 1) 
 
SAC 
4.4.  
PK 
PK17 
Individual Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log)– Cycle 1 (Part 1) 
 
SAC 
4.5.  
PK 
PK17 
Individual Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) by Dose (Part 
1) 
 
SAC 
4.6.  
PK 
PK17 
Individual Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 1) 
 
SAC 
4.7.  
PK 
PK17 
Individual Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) by Dose – 
Cycle 1 (Part 1) 
 
SAC 
4.8.  
PK 
PK17 
Individual Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) – Cycle 1 
(Part 1) 
 
SAC 
4.9.  
PK 
PK17 
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) by Dose (Part 1) 
 
SAC 


 
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Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
4.10. 
PK 
PK17 
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) by Dose - Limit the Maximum 
Concentration Value of 3000 (Part 1) 
Maximum value of vertical axis is 
3000. 
SAC 
4.11. 
PK 
PK17 
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) (Part 1) 
 
SAC 
4.12. 
PK 
PK17 
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) - Limit the Maximum Concentration 
Value of 3000 (Part 1) 
Maximum value of vertical axis is 
3000. 
SAC 
4.13. 
PK 
PK17 
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) by Dose – Cycle 1 (Part 1) 
 
SAC 
4.14. 
PK 
PK17 
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) by Dose – Cycle 1, Limit the Maximum 
Concentration Value of 3000 (Part 1) 
Maximum value of vertical axis is 
3000. 
SAC 
4.15. 
PK 
PK17 
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) – Cycle 1 (Part 1) 
 
SAC 
4.16. 
PK 
PK17 
Individual Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) – Cycle 1, Limit the Maximum 
Concentration Value of 3000 (Part 1) 
Maximum value of vertical axis is 
3000. 
SAC 
4.17. 
PK 
PK17 
Mean (+SD) Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) (Part 1) 
 
SAC 
4.18. 
PK 
PK17 
Mean (+SD) Plasma GSK2857916 (ADC) Concentration-Time 
Plots (Linear and Semi-Log) – Cycle 1 (Part 1) 
 
SAC 
4.19. 
PK 
PK17 
Mean (+SD) Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 1) 
 
SAC 


 
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Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
4.20. 
PK 
PK17 
Mean (+SD) Plasma GSK2857916 (Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) – Cycle 1 
(Part 1) 
 
SAC 
4.21. 
PK 
PK17 
Mean (+SD) Plasma GSK2857916 (ADC and Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 1) 
 
SAC 
4.22. 
PK 
PK17 
Mean (+SD) Plasma GSK2857916 (ADC and Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) – Cycle 1 
(Part 1) 
See similar Fig14.0190 from 
BMA117159 (Primary_01) 
SAC 
4.23. 
PK 
PK17 
Mean (+SD) Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) (Part 1) 
 
SAC 
4.24. 
PK 
PK17 
Mean (+SD) Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) – Cycle 1 (Part 1) 
 
SAC 
4.25. 
PK 
PK18 
Median Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) (Part 1) 
 
SAC 
4.26. 
PK 
PK18 
Median Plasma GSK2857916 (ADC) Concentration-Time Plots 
(Linear and Semi-Log) – Cycle 1 (Part 1) 
 
SAC 
4.27. 
PK 
PK18 
Median Plasma GSK2857916 (Total Antibody) Concentration-
Time Plots (Linear and Semi-Log) (Part 1) 
 
SAC 
4.28. 
PK 
PK18 
Median Plasma GSK2857916 (Total Antibody) Concentration-
Time Plots (Linear and Semi-Log) – Cycle 1 (Part 1) 
 
SAC 
4.29. 
PK 
PK18 
Median Plasma GSK2857916 (ADC and Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) (Part 1) 
See similar Fig14.0200 from 
BMA117159 (Primary_01) 
SAC 
4.30. 
PK 
PK18 
Median Plasma GSK2857916 (ADC and Total Antibody) 
Concentration-Time Plots (Linear and Semi-Log) – Cycle 1 
(Part 1) 
 
SAC 


 
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Pharmacokinetic: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
4.31. 
PK 
PK18 
Median Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) (Part 1) 
 
SAC 
4.32. 
PK 
PK18 
Median Plasma cys-mcMMAF Concentration-Time Plots 
(Linear and Semi-Log) – Cycle 1 (Part 1) 
 
SAC 
4.33. 
PK 
PK28 
Plot of Individual (+Geometric Mean and 95%CI) of 
Accumulation Ratios for GSK2857916 Analytes (Linear and 
Semi-Log) (Part 1) 
Plot accumulation ratios versus 
dose. 
Add a reference line at 1. 
Plot Ro(Ctrough) and Ro(Ceoi) on 
different plots. Only include 
geometric mean and 95%CI. 
Plot analytes: ADC, total antibody, 
and cys-mcMMAF on the same 
plot. 
SAC 


 
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14.10.14. ICH Listings 
ICH: Listings 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Subject Disposition 
1.  
All Treated 
ES2 
Listing of Reasons for Study Withdrawal (Part 1) 
ICH E3 
Add column for Relatedness to 
COVID-19 
SAC 
2.  
All Treated 
SD2 
Listing of Reasons for Study Treatment Discontinuation (Part 1) 
ICH E3 
The listing will include last dose 
date, and reasons for study 
treatment discontinuation. 
Add column for Relatedness to 
COVID-19 
SAC 
Protocol Deviations 
3.  
All Treated 
DV2 
Listing of Protocol Deviations (Part 1) 
Including a column “Important or 
not” 
SAC 
4.  
All Treated 
IE3 
Listing of Participants with Inclusion/Exclusion Criteria 
Deviations (Part 1) 
ICH E3 
SAC 
Populations Analysed 
5.  
All Treated 
SP3 
Listing of Participants Excluded from Any Population (Part 1) 
ICH E3 
SAC 
Demographic and Baseline Characteristics 
6.  
All Treated 
DM2 
Listing of Demographic Characteristics (Part 1) 
ICH E3 
SAC 
7.  
All Treated 
DM9 
Listing of Race (Part 1) 
ICH E3 
SAC 
Exposure and Treatment Compliance 
8.  
All Treated 
TA1 
Listing of Planned and Actual Treatments for Subjects with 
Actual Starting Dose Different from Assigned Dose (Part 1) 
ICH E3 
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ICH: Listings 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
9.  
All Treated 
OEX8A 
Listing of Exposure Data to GSK2857916 (Part 1) 
Include start and stop dates, 
scheduled and actual dose, # of 
days on study treatment; sort by 
part, disease cohort, center, and 
subject id 
SAC 
10.  
All Treated 
ODMOD12A 
Listing of Dose Delays (Part 1) 
ICH E3 
SAC 
11.  
All Treated 
ODMOD10A 
Listing of Dose Reductions (Part 1) 
ICH E3 
SAC 
12.  
All Treated 
ODMOD17A 
Listing of Infusion Interruptions (Part 1) 
ICH E3 
SAC 
13.  
All Treated 
ODMOD14A 
Listing of Incomplete Infusions (Part 1) 
ICH E3 
SAC 
14.  
All Treated 
OEX9 
Summary Listing of Overall Exposure and Dose Modifications 
(Part 1) 
 
SAC 
Dose-Limiting Toxicity 
15.  
DLT 
Evaluable 
DL3 
Listing of Dose-Limiting Toxicities during the Determinative 
Period (Part 1) 
ICH E3 
Add footnote: “The determinative 
period is the first 21 days of 
intervention” 
SAC 
Adverse Events 
16.  
All Treated 
OAE04 
Listing of Adverse Events (Part 1) 
ICH E3 
SAC 
17.  
All Treated 
OAE03 
Listing of Subject Numbers for Individual Adverse Events (Part 
1) 
ICH E3 
SAC 
18.  
All Treated 
AE2 
Listing of Relationship Between Adverse Event System Organ 
Classes, Preferred Terms, and Verbatim Text (Part 1) 
IDSL 
SAC 
19.  
All Treated 
OAE04 
Listing of Treatment Emergent Adverse Events (Part 1) 
ICH E3 
SAC 
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ICH: Listings 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
20.  
All Treated 
DTH3 
Listing of Deaths (Part 1) 
 
SAC 
21.  
All Treated 
OAE04 
Listing of Fatal Serious Adverse Events (Part 1) 
 
SAC 
22.  
All Treated 
OAE04 
Listing of Non-Fatal Serious Adverse Events (Part 1) 
 
SAC 
23.  
All Treated 
OAE04 
Listing of Adverse Events Leading to Permanent 
Discontinuation of Study Treatment (Part 1) 
Based on Action taken on AE 
SAC 
24.  
All Treated 
OAE04 
Listing of Adverse Events Leading to Dose Reductions for 
GSK2857916 (Part 1) 
 
SAC 
25.  
All Treated 
OAE04 
Listing of Adverse Events Leading to Dose Interruptions/Dose 
Delays for GSK2857916 (Part 1) 
 
SAC 
26.  
All Treated 
OAE04 
Listing of Adverse Events Leading to Infusion Interruptions for 
GSK2857916 (Part 1) 
ICH E3 
 
SAC 
27.  
All Treated 
OAE04 
Listing of Adverse Events Leading to Incomplete Infusions for 
GSK2857916 (Part 1) 
ICH E3 
 
SAC 
28.  
All Treated 
OAE04 
Listing of Corneal Events (GSK Scale) (Part 1) 
 
SAC 
29.  
All Treated 
OAE04 
Listing of Thrombocytopenia (Part 1) 
 
SAC 
30.  
All Treated 
OAE04 
Listing of Infusion Related Reactions (Part 1) 
 
SAC 
Hepatobiliary (Liver) 
31.  
All Treated 
MH2 
Listing of Medical Conditions for Participants with Liver 
Stopping Events (Part 1) 
IDSL 
SAC 
32.  
All Treated 
SU2 
Listing of Substance Use for Participants with Liver Stopping 
Events (Part 1) 
IDSL 
SAC 
All Laboratory 
33.  
All Treated 
OLB7 
Listing of All Laboratory Data for Subjects with Lab Values of 
Potential Clinical Importance (Part 1) 
ICH E3 
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ICH: Listings 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
34.  
All Treated 
UR2A 
Listing of Urinalysis Data for Subjects with Any Value of 
Potential Clinical Importance (Part 1) 
 
SAC 
35.  
All Treated 
OLB7 
Listing of eGFR for Subjects with Lab Values Outside of 
Normal Range (Part 1) 
 
SAC 
36.  
All Treated 
LB14 
Listing of Laboratory Data with Character Results (Part 1) 
 
SAC 
Performance Status 
37.  
All Treated 
PS5A 
Listing of ECOG Performance Status (Part 1) 
 
SAC 
ECG 
38.  
All Treated 
EG3 
Listing of ECG Values of Potential Clinical Importance (Part 1) 
 
SAC 
39.  
All Treated 
EG5 
Listing of Abnormal ECG Findings (Part 1) 
IDSL 
SAC 
LVEF 
40.  
All Treated 
OLVEF2A 
Listing of Left Ventricular Ejection Fraction Results (Part 1) 
 
SAC 
Vital Signs 
41.  
All Treated 
OVT7A 
Listing of All Vital Signs Data for Subjects with Any Value of 
Potential Clinical Importance (Part 1) 
IDSL 
Display ALL Vital Signs for a 
subject who experienced a value of 
potential clinical importance. 
SAC 
42.  
All Treated 
OVT7A 
Listing of All Vital Signs Data for Subjects (Part 1) 
IDSL 
SAC 
Anti-Drug Antibody 
43.  
All Treated 
ADA01 
Listing of Anti-GSK2857916 Antibody Results (Part 1) 
 
SAC 
Pharmacokinetic 
44.  
PK 
PK07 
Listing of Plasma GSK2857916 (ADC) Pharmacokinetic 
Concentration-Time Data (Part 1) 
 
SAC 


 
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ICH: Listings 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
45.  
PK 
PK07 
Listing of Plasma GSK2857916 (Total Antibody) 
Pharmacokinetic Concentration-Time Data (Part 1) 
 
SAC 
46.  
PK 
PK07 
Listing of Plasma cys-mcMMAF Pharmacokinetic 
Concentration-Time Data (Part 1) 
 
SAC 
47.  
PK 
PK15 
Listing of GSK2857916 (ADC) Accumulation Ratio (Part 1) 
 
SAC 
48. 
PK 
PK15 
Listing of GSK2857916 (Total Antibody) Accumulation Ratio 
(Part 1) 
 
SAC 
49.  
PK 
PK15 
Listing of cys-mcMMAF Accumulation Ratio (Part 1) 
 
SAC 
Efficacy 
52.  
All Treated 
RE5 
Listing of Investigator - Assessed Responses (with and without 
confirmation) per IMWG Response Criteria (Part 1) 
 
SAC 
53.  
All Treated 
RE5 
Listing of Extramedullary Disease Evaluation (Part 1) 
 
SAC 
54.  
All Treated 
RE5 
Listing of Skeletal Survey (Part 1) 
 
SAC 
 
 
 
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14.10.15. Non-ICH Listings 
Non-ICH: Listings 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Demographic and Baseline Characteristics 
55.  
All Treated 
SU2 
Listing of Substance Use (Part 1) 
 
SAC 
56.  
All Treated 
DC3 
Listing of Disease Characteristics at Initial Diagnosis (Part 1) 
 
SAC 
57.  
All Treated 
DC4 
Listing of Disease Characteristics at Screening (Part 1) 
 
SAC 
58.  
All Treated 
DC4 
Listing of Genetic Characteristics and Cytogenetic Risk (Part 1) 
 
SAC 
Prior and Concomitant Medications 
59.  
All Treated 
CM2 
Listing of Prior Medications (Part 1) 
 
SAC 
60.  
All Treated 
CM2 
Listing of Concomitant Medications (Part 1) 
 
SAC 
61.  
All Treated 
CM2 
Listing of Blood Products on Treatment (Part 1) 
 
SAC 
62.  
All Treated 
CM2 
Listing of Blood Supportive Care Products on Treatment (Part 
1) 
 
SAC 
63.  
All Treated 
CM2 
Listing of Stem Cell Mobilization Products on Treatment (Part 
1) 
 
SAC 
64.  
All Treated 
CM2 
Listing of Eye Medications (Part 1) 
 
SAC 
Medical Conditions 
65.  
All Treated 
MH2 
Listing of Prior Medical Conditions (Part 1) 
 
SAC 
66.  
All Treated 
CM2 
Listing of Current Medical-Conditions (Part 1) 
 
SAC 
Anti-Cancer Therapy 
67.  
All Treated 
AC6 
Listing of Prior Anti-Cancer Therapy (Part 1) 
 
SAC 
68.  
All Treated 
AC6 
Listing of Follow-up Anti-Cancer Therapy (Part 1) 
 
SAC 


 
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Non-ICH: Listings 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
69.  
All Treated 
AC7 
Listing of Prior, On treatment, and Follow-up Anti-Cancer 
Radiotherapy (Part 1) 
 
SAC 
70.  
All Treated 
OSP3 
Listing of Prior, On Treatment, and Follow-up Cancer and Non-
Cancer Related Surgical Procedure (Part 1) 
 
SAC 
71.  
All Treated 
OSP3 
Listing of Stem Cell Transplant (Part 1) 
 
SAC 
Ocular Exam 
72.  
All Treated 
[Non-Standard] 
SAFE_L1 
Listing of Visual Acuity Results (Part 1) 
 
SAC 
73.  
All Treated 
[Non-Standard] 
SAFE_L1 
Listing of Conjunctival Exam Results (Part 1) 
 
SAC 
74.  
All Treated 
[Non-Standard] 
SAFE_L1 
Listing of Slit Lamp Anterior Chamber, Slit Lamp Iris and Slit 
Lamp Lens Exam Results (Part 1) 
 
SAC 
75.  
All Treated 
[Non-Standard] 
SAFE_L1 
Listing of Indirect Fundoscopic Exam (Part 1) 
 
SAC 
76.  
All Treated 
[Non-Standard] 
SAFE_L1 
Listing of Pupillary Exam Results (Part 1) 
 
SAC 
77.  
All Treated 
[Non-Standard] 
SAFE_L1 
Listing of Extraocular Muscle Movement and External Exam 
Results (Part 1) 
 
SAC 
78.  
All Treated 
[Non-Standard] 
SAFE_L1 
Listing of Lids, Lashes, Lacrimal System Exam and Scleritis 
Results (Part 1) 
 
SAC 
79.  
All Treated 
[Non-Standard] 
SAFE_L1 
Listing of Corneal Results (Part 1) 
 
SAC 


 
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14.11. 
Appendix 11: Example Mock Shells for Data Displays 
Mock shells for data displays will be prepared separately from the RAP. 
 
 


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207504 
109 
 
 
14.12. 
Appendix 12: International Myeloma Working Group Uniform 
Response Criteria for Multiple Myeloma 
Response 
IMWG Criteria 
Stringent complete 
response (sCR) 
• 
Complete response as defined below plus normal FLC ratio1 and absence of clonal 
cells in bone marrow biopsy by immunohistochemistry (κ/λ ratio ≤4:1 or ≥1:2 for κ 
and λ patients, respectively, after counting ≥100 plasma cells)2 
Complete response 
(CR) 
• 
Negative immunofixation on the serum and urine and disappearance of any soft 
tissue plasmacytomas and < 5% plasma cells in bone marrow3 
Very good partial 
response (VGPR) 
• 
Serum and urine M-protein detectable by immunofixation but not on electrophoresis 
or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 h 
Partial response (PR) 
• 
≥50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by 
≥90% or to <200 mg per 24 h; 
• 
If the serum and urine M-protein are unmeasurable, a ≥50% decrease in the 
difference between involved and uninvolved FLC levels is required in place of the 
M-protein criteria; 
• 
If serum and urine M-protein are unmeasurable, and serum-free light assay is also 
unmeasurable, ≥50% reduction in plasma cells is required in place of M-protein, 
provided baseline bone marrow plasma-cell percentage was ≥30%. In addition to 
these criteria, if present at baseline, a ≥50% reduction in the size (SPD)4 of soft 
tissue plasmacytomas is also required 
Minimal response 
(MR) 
• 
≥25% but ≤49% reduction of serum M-protein and reduction in 24-h urine M-protein 
by 50–89%. In addition to the above listed criteria, if present at baseline, a ≥50% 
reduction in the size (SPD)4 of soft tissue plasmacytomas is also required 
Stable 
Disease (SD) 
• 
Not recommended for use as an indicator of response; stability of disease is best 
described by providing the time-to-progression estimates. Not meeting criteria for 
complete response, very good partial response, partial response, minimal response, 
or progressive disease 
Progressive disease 
(PD)5,6  
Any one or more of the following criteria: 
• 
Increase of 25% from lowest confirmed response value in one or more of the 
following criteria: 
    - Serum M-protein (absolute increase must be ≥0·5 g/dL); 
    - Serum M-protein increase ≥1 g/dL, if the lowest M component was ≥5 g/dL; 
    - Urine M-protein (absolute increase must be ≥200 mg/24 h); 
• 
In participants without measurable serum and urine M-protein levels, the difference 
between involved and uninvolved FLC levels (absolute increase must be >10 
mg/dL); 
• 
In participants without measurable serum and urine M-protein levels and without 
measurable involved FLC levels, bone marrow plasma-cell percentage irrespective 
of baseline status (absolute increase must be ≥10%); 
• 
Appearance of a new lesion(s), ≥50% increase from nadir in SPD4 of >1 lesion, or 
≥50% increase in the longest diameter of a previous lesion >1 cm in short axis; 
• 
≥50% increase in circulating plasma cells (minimum of 200 cells per μL) if this is the 
only measure of disease 
Relapse 
Clinical relapse requires one or more of: 


CONFIDENTIAL 
 
 
207504 
110 
 
 
 
 
 
 
 
 
 
• 
Direct indicators of increasing disease and/or end organ dysfunction (CRAB 
features) related to the underlying clonal plasma-cell proliferative disorder. It is not 
used in calculation of time to progression or progression-free survival but is listed as 
something that can be reported optionally or for use in clinical practice; 
• 
Development of new soft tissue plasmacytomas or bone lesions (osteoporotic 
fractures do not constitute progression); 
• 
Definite increase in the size of existing plasmacytomas or bone lesions. A definite 
increase is defined as a 50% (and ≥1 cm) increase as measured serially by the 
SPD§§ of the measurable lesion; 
• 
Hypercalcaemia (>11 mg/dL); 
• 
Decrease in haemoglobin of ≥2 g/dL not related to therapy or other non-myeloma-
related conditions; 
• 
Rise in serum creatinine by 2 mg/dL or more from the start of the therapy and 
attributable to myeloma; 
• 
Hyperviscosity related to serum paraprotein 
Overall Responders: PR, VGPR, CR, sCR 
Clinical Benefit Rate: Overall responders + MR 
Adapted from Kumar et.al. Lancet Oncol 2016; 17: e328–46 
1 All recommendations regarding clinical uses relating to serum FLC levels or FLC ratio are based on results obtained with 
the validated Freelite test (Binding Site, Birmingham, UK).  
2 Presence/absence of clonal cells on immunohistochemistry is based upon the κ/λ/L ratio. An abnormal κ/λ ratio by 
immunohistochemistry requires a minimum of 100 plasma cells for analysis. An abnormal ratio reflecting presence of an 
abnormal clone is κ/λ of >4:1 or <1:2.  
3 Special attention should be given to the emergence of a different monoclonal protein following treatment, especially in the 
setting of participants having achieved a conventional complete response, often related to oligoclonal reconstitution of the 
immune system. These bands typically disappear over time and in some studies have been associated with a better outcome. 
Also, appearance of monoclonal IgG κ in participants receiving monoclonal antibodies should be differentiated from the 
therapeutic antibody.  
4 Plasmacytoma measurements should be taken from the CT portion of the PET/CT, or MRI scans, or dedicated CT scans 
where applicable. For participants with only skin involvement, skin lesions should be measured with a ruler. Measurement of 
tumour size will be determined by the SPD. 
5 Positive fixation alone in a participant previously classified as achieving a complete response will not be considered 
progression. For purposes of calculating time to progression and progression-free survival, participants who have achieved a 
complete response and are MRD-negative should be evaluated using criteria listed for progressive disease. Criteria for 
relapse from a complete response or relapse from MRD should be used only when calculating disease-free survival.  
6 In the case where a value is felt to be a spurious result per physician discretion (e.g. a possible laboratory error), 
that value will not be considered when determining the lowest value. 


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
207504 
Page 1 of 45 
Information Type: 
Statistical Analysis Plan (SAP) Amendment for 
Part 2 
TITLE PAGE 
Protocol Title: 
A Phase I Open-Label, Dose Escalation Study to Investigate the 
Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, 
Immunogenicity and Clinical Activity of the Antibody Drug 
Conjugate GSK2857916 in Japanese Participants with 
Relapsed/Refractory Multiple Myeloma 
Study Number: 
207504 
Compound Number: 
GSK2857916 
Abbreviated Title: 
A Phase I open label, dose escalation study in Japanese participants 
with relapsed/refractory multiple myeloma who have failed prior 
anti-myeloma treatments. 
Acronym: 
BCMA 
Sponsor Name: GlaxoSmithKline Research & Development Limited 
Regulatory Agency Identifier Number(s): Not applicable 
SAP Author(s): 
Author 
Date 
 
26-APR-2023
Senior Biostatistician, Biostatistics FSP,  
PAREXEL employee on behalf of GlaxoSmithKline K.K. 
Copyright 2022 the GlaxoSmithKline group of companies. All rights reserved.  Unauthorised 
copying or use of this information is prohibited. 
PPD


CONFIDENTIAL 
The GlaxoSmithKline group of companies 
207504 
Page 2 of 45 
Parexel Review Confirmations (Method: E-mail) 
Reviewer 
Date 
 
27-APR-2023
Senior Data Management Lead, 
Parexel International 
 
27-APR-2023
Senior Principal Statistical Programmer, Statistical Programming 
FSP, Parexel International 
 
27-APR-2023
Medical Writer, Medical Writing Services, 
Parexel International 
GSK Review Confirmations (Method: E-mail) 
Reviewer 
Date 
 
27-APR-2023
Statistician, Biostatistics, Japan Medical and Development, 
GlaxoSmithKline K.K. 
 
27-APR-2023
Study Accountable Person, Clinical Development (Oncology), 
Oncology Medical and Development, Japan Medical and 
Development, GlaxoSmithKline K.K. 
 
27-APR-2023
Programmer, Clinical Programming, Biostatistics, Japan Medical and 
Development, GlaxoSmithKline K.K. 
 
27-APR-2023
Medical Writer, Medical Writing, Clinical Operations and Platforms, 
Japan Medical and Development, GlaxoSmithKline K.K. 
 
27-APR-2023
Clinical Pharmacology Scientist, Clinical Pharmacology Modeling & 
Simulation Japan, GlaxoSmithKline K.K. 
GSK Clinical Statistics & Clinical Programming Line Approvals 
(Method: E-mail) 
Approver 
Date 
28-APR-2023
 Dev Biostats Stats Oncology, GlaxoSmithKline 
K.K. 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
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Page 3 of 45 
TABLE OF CONTENTS 
PAGE 
1.
INTRODUCTION ...................................................................................................... 6 
1.1. 
Objectives and Endpoints ............................................................................. 6 
1.2. 
Study Design ................................................................................................ 7 
2.
STATISTICAL HYPOTHESES ................................................................................. 8 
2.1. 
Multiplicity Adjustment .................................................................................. 8 
3.
ANALYSIS SETS ..................................................................................................... 9 
4.
STATISTICAL ANALYSES ....................................................................................... 9 
4.1. 
General Considerations ................................................................................ 9 
4.1.1. 
General Methodology .................................................................. 10 
4.1.2. 
Baseline Definition ....................................................................... 10 
4.2. 
Primary Endpoints Analyses ....................................................................... 11 
4.2.1. 
Definition of Endpoints ................................................................. 11 
4.2.2. 
Main Analytical Approach ............................................................ 12 
4.3. 
Secondary Endpoints Analyses .................................................................. 15 
4.3.1. 
Pharmacokinetics ........................................................................ 15 
4.3.2. 
Safety .......................................................................................... 17 
4.3.3. 
Efficacy ........................................................................................ 18 
4.5. 
Other Safety Analyses ................................................................................ 22 
4.5.1. 
Vital Signs .................................................................................... 22 
4.5.2. 
Electrocardiograms ...................................................................... 22 
4.5.3. 
Ocular Exams .............................................................................. 23 
4.5.4. 
Left Ventricular Ejection Fraction ................................................. 23 
4.5.5. 
Other Safety Measures ................................................................ 24 
4.5.6. 
Extent of Exposure ...................................................................... 24 
4.6. 
Other Analyses ........................................................................................... 25 
4.6.1. 
Population Pharmacokinetic (POPPK) Analyses .......................... 25 
4.6.2. 
Pharmacokinetic / Pharmacodynamic Analyses ........................... 25 
4.7. 
Interim Analyses ......................................................................................... 26 
4.8. 
Planned Analyses ....................................................................................... 26 
4.9. 
Changes to Protocol Defined Analyses ....................................................... 26 
5.
SAMPLE SIZE DETERMINATION ......................................................................... 26 
6.
SUPPORTING DOCUMENTATION ....................................................................... 26 
6.1. 
Appendix 1 Study Population Analyses ....................................................... 26 
6.1.1. 
Participant Disposition ................................................................. 27 
6.1.2. 
Demographic and Baseline Characteristics .................................. 27 
6.1.3. 
Protocol Deviations ...................................................................... 28 
6.1.4. 
Prior and Concomitant Medications ............................................. 28 
6.1.5. 
Additional Analyses Due to the COVID-19 Pandemic .................. 28 
6.2. 
Appendix 2 Clinical Laboratory Tests .......................................................... 29 
6.3. 
Appendix 3 Schedule of Activities (SoA) ..................................................... 32 
CCI


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Page 4 of 45 
6.4. 
Appendix 4 Data Derivations Rule .............................................................. 33 
6.4.1. 
Criteria for Potential Clinical Importance ...................................... 33 
6.4.2. 
Study Phases .............................................................................. 33 
6.4.3. 
Study Day and Reference Dates .................................................. 34 
6.4.4. 
Assessment Window ................................................................... 35 
6.4.5. 
Treatment Emergent Flag for Adverse Events ............................. 35 
6.4.6. 
Multiple measurements at One Analysis Time Point .................... 35 
6.4.7. 
Handling of Partial Dates ............................................................. 35 
6.5. 
Appendix 5 International Myeloma Working Group Uniform 
Response Criteria for Multiple Myeloma ..................................................... 37 
6.6. 
Appendix 6 Abbreviations ........................................................................... 40 
Trademarks ................................................................................................ 43 
7.
REFERENCES ....................................................................................................... 44 


CONFIDENTIAL 
 
  
Page 5 of 45 
Version history 
SAP 
Version 
Approval 
Date 
Protocol 
Version (Date) 
on which SAP 
is Based 
Change 
Rationale 
1.0 
27-APR-
2022 
Amendment 5 
(12-NOV-2021) 
Not Applicable 
Original 
version 
Amendment 
1 
X-APR-2023 
Amendment 6 
(10-Feb-2023) 
1.Section 1.2 – To add the 
Post Analysis Continued 
Treatment (PACT) after final 
analysis data cut-off (DCO) 
2.Section 3 & 4.2.2.1 – To 
clarify the definition for the 
ratio of the actual dose to the 
planned dose in terms of the 
DLT evaluable population 
3.Section 4.3.3.2.2- To add 
the profile plot of 
GSK2857916 and response 
4.Section 4.3.1.2.2 & 4.4.1.2 – 
To add how to address the 
calculation of SD when n is 
small 
5.Section 4.3.3.2- To modify 
the confirmed response of #11 
from NE to SD based on 
global project’s policy 
change6. Section 6.1.1- To 
include “Participants who 
move to PACT” in the listing 
7.Section 6.1.2-To remove the 
description of the “Race and 
Race combination will be 
summarised” 
Changes 
followed 
the Protocol 
Amendment 
3  
 


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Page 6 of 45 
1. 
INTRODUCTION 
The purpose of this statistical analysis plan (SAP) is to describe the planned analyses to be 
included in the Clinical Study Report for Protocol:  RPS-CLIN-050928 (Dated: 10-FEB-2023).  
This SAP focuses on the analysis plan for combination therapy (Part 2). Reporting and analysis 
plan (RAP) focused on the analysis plan for monotherapy (Part 1) had been developed in a 
separate document and the analysis for Part 1 was completed on 28-JAN-2022.  
Note that in line with the guidelines, this SAP will use the term “participant”, while all data 
displays (Tables, Figures & Listings [TFL]) produced as part of the planned dry-run and 
Statistical Analysis Complete (SAC), will use the term “subject” which reflects GSK Data 
Display Standards terminology.  
1.1. 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
 
• 
To evaluate safety, tolerability of GSK2857916 
in Japanese participants RRMM. 
• 
Number of participants with drug limiting 
toxicities (DLTs) 
• 
Adverse events (AEs) and changes in clinical 
signs and laboratory parameters. 
Secondary 
 
• 
To evaluate pharmacokinetic (PK) profile of 
GSK2857916 and cysteine maleimidocaproyl 
monomethyl auristatin F (cys-mcMMAF) after 
IV single and repeat dose administration in 
Japanese participants with RRMM. 
• 
GSK2857916 and cys-mcMMAF PK 
parameters following IV single and repeat 
dose administration as data permit (e.g., 
AUCs, Cmax, tmax, CL, Vss, t½ [single 
dose], Ceoi, Ctrough, and Rac (Ceoi and 
Ctrough) [repeat dose]). 
• 
To assess anti-drug antibody (ADA) formation 
after IV single and repeat dose administration 
of GSK2857916. 
• 
ADA incidence and titers after IV single and 
repeat dosing of GSK2857916. 
• 
To investigate the initial anti-tumor activity of 
GSK2857916 in Japanese participants with 
RRMM. 
• 
Clinical activity measured as Overall 
Response Rate (ORR) and Clinical Benefit 
Rate (CBR) which are defined as follows: 
o ORR: the percentage of participants 
achieving confirmed partial response or 
better (PR) 
o CBR: the percentage of participants with 
minimal response (MR) or better 


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Objectives 
Endpoints 
1.2. 
Study Design 
Overview of Study Design and Key Features 
Design 
Features 
•
This is a Phase 1, open label study of the antibody drug conjugate GSK2857916 in
Japanese participants with relapsed/refractory multiple myeloma.
•
This study consists of 2 parts (Part 1 and Part 2).
•
Part 1 was dose escalation phase to evaluate the safety and tolerability of up to 2 dose
levels of GSK2857916 monotherapy.
•
Part 2 will evaluate the safety of tolerability of 1 dose level of GSK2857916 in combination
with 2 standard of care (SoC) regimens: Arm A – GSK2857916 with Bortezomib and
Dexamethasone (Bor/Dex), and Arm B – GSK2857916 with Pomalidomide and
Dexamethasone (Pom/Dex).
•
The dose escalation model in Part 1 was based on 3 + 3 design. The maximum number of
participants was up to 12, up to 6 participants each for 2.5 mg/kg cohort and 3.4 mg/kg
cohort. The maximum number of participants for Part 2 will be up to 12, up to 6 participants
each for Arm A and Arm B based on 3 + 3 design. If participants prematurely discontinue
during the DLT evaluation period for reasons other than toxicity, additional participants may
be enrolled as replacement participants and assigned to the same dose level at the
discretion of the Sponsor and in consultation with the investigator
•
In Part 1, GSK2857916 was given on a once every 21 days schedule. In Part 2, GSK
2857916 will be given in combination with Bor/Dex on a once every 21 days schedule (Arm
A) or with Pom/Dex on a once every 28 days schedule (Arm B).
•
The initial anti-tumor activity of GSK2857916 based on response assessment criteria as
defined by International Myeloma Working Group (IMWG) 2016 will also be assessed
during the study [Kumar, 2016].
•
A final DCO representing the end of data collection, prior to the End of Study
(EOS), is defined as 21 months post last subject first dose. Following the final DCO
date the study will move into the PACT phase and the clinical study database will
be closed to new data. Participants who are receiving study treatment may continue
to receive study treatment if they are gaining clinical benefit as assessed by the
investigator until they meet any protocol-defined treatment discontinuation criteria.
Although the clinical study database will be closed at the time of the final DCO date,
the study remains open until all participants discontinue study treatment and
complete the 70-day safety follow-up and the EOS definition is reached.
•
The EOS is defined as the date of the last visit of the last participant in the study
(e.g. last dose plus 70 days AE reporting period) or last scheduled procedure
CCI


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Overview of Study Design and Key Features 
shown in the protocol Section 1.3 Schedule of Activities for the last participant in the 
study. 
Treatment 
•
In Part 1, GSK2857916 was IV administered, via an infusion pump on Day 1 of each cycle
over 30 minutes. Premedication was not required prior to infusion unless deemed medically
necessary by the investigator, in which case it had been administered according to
institutional recommendations.
•
In Part 2, GSK2857916 is IV administered via an infusion pump. Arm A receives 2.5 mg/kg
on Day 1 of each cycle, once every 3 weeks. In addition, Arm A receives 1.3 mg/m2
Bortezomib via subcutaneous injection on Day 1, Day 4, Day 8, Day 11 once every 3 weeks
(Q3W) for 8 cycles and 20 mg Dexamethasone orally on Day 1, Day 2, Day 4, Day 5, Day
8, Day 9, Day 11, and Day 12, Q3W for 8 cycles. Arm B receives 2.5 mg/kg of
GSK2857916 on Day 1 of Cycle 1 and 1.9 mg/kg on Cycle 2 Day 1 and beyond, once every
4 weeks. In addition, Arm B receives 4 mg  Pomalidomide orally daily on Days 1-21, once
every 4 weeks (Q4W) and 40 mg Dexamethasone orally per day on Day 1, Day 8, Day 15,
and Day 22 Q4W.
Treatment 
Assignment 
•
This is an open-label study and consists of two parts (Part 1, Part 2). There are two cohorts
(2.5 mg/kg and 3.4 mg/kg) in Part 1 and one cohort for each arm in Part 2 (2.5 mg/kg with
Bor/Dex for Arm A, 2.5 mg/kg at C1D1 and 1.9 mg/kg at C2D1 with Pom/Dex for Arm B).
Time & 
Events 
•
Refer to protocol Section 1.3 Schedule of Activities
Interim 
Analysis 
•
In Part 1, available safety data was reviewed after the completion of DLT evaluation period
to determine if a dose-escalation is appropriate. Additionally, PK data was reviewed after
the completion of DLT evaluation period to assess PK similarity between Japanese and
overseas populations.
•
For Part 2, available safety data will be reviewed after the completion of DLT evaluation
period per each arm to determine if the combination dose regimen is tolerable. An interim
analysis may be conducted when the last participant within each arm in Part 2 is followed
for at least 1 cycle to evaluate safety, efficacy and PK profiles.
2.
STATISTICAL HYPOTHESES
The primary objective is to evaluate safety, tolerability of GSK2857916 in Japanese participants 
RRMM. There are no formal statistical hypotheses planned.  
2.1. 
Multiplicity Adjustment 
No formal statistical comparison will be performed; therefore, no adjustments for multiple 
comparisons or multiplicity are planned. 


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Page 9 of 45 
3. 
ANALYSIS SETS 
Analysis Set 
Definition / Criteria 
Analyses Evaluated 
Screened  
• All participants who were screened for eligibility. 
• Study 
Population 
All Treated 
 
• All participants who received at least 1 dose of study 
treatment. 
• An incorrect treatment schedule or study treatment 
administration or an early termination of treatment 
will not result in exclusion of participants from this 
population. 
• Study 
Population 
• Safety 
• Efficacy 
• Immunogenicity 
DLT Evaluable 
• All participants fulfilling the ‘All Treated’ population 
criteria and having received a complete infusion of 
GSK2857916 and at least 75% of planned doses of 
bortezomib/dexamethasone (Arm A) or 
pomalidomide/dexamethasone (Arm B) in Cycle 1. 
• 
Participants who have been withdrawn from the 
study for reasons other than toxicity but prior to the 
21-day DLT observation period (Arm A) and the 28-
day DLT observation period (Arm B) are not included 
in this population. 
• 
The ratio of the actual dose to the planned dose of 
bortezomib/dexamethasone (Arm A) or 
pomalidomide/dexamethasone (Arm B) is to be 
calculated as the average of actual dose/planned 
dose for each drug (Bortezomib and 
dexamethasone, or Pomalidomide and 
dexamethasone) administered to Cycle 1. 
• Summary of 
DLT 
Pharmacokinetic 
(PK) 
• 
All participants in the ‘All Treated’ population who 
had at least 1 non-missing PK assessment (Non-
quantifiable [NQ] values will be considered as non-
missing values). 
• PK 
Pharmacodynamic 
(PD) 
• All participants in the ‘All Treated’ population from 
whom at least one PD sample is obtained, analyzed, 
and is measurable. 
• PD 
 
4. 
STATISTICAL ANALYSES 
4.1. 
General Considerations 
Given that no formal statistical hypotheses are being tested in this study, analysis of the data 
obtained from the study will only utilize descriptive methods. 


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Page 10 of 45 
4.1.1. 
General Methodology 
Participants who prematurely withdrew from study will not be replaced. However, participants in 
Part 2 who have received less than 1 full dose of GSK2857916, or less than 75% of planned 
doses of Bor/Dex or Pom/Dex, or who have been withdrawn from the study for reasons other 
than toxicity but prior to completion of DLT observation period will be replaced. 
Part 2 result will be reported with separate outputs unless otherwise stated. Results will be 
presented for Arm A and Arm B separately. The treatment display format is specified in Output 
and Programming Specification (OPS) Section 4.2 Appendix 2 Study Treatment Group and 
Descriptions.  
Unless otherwise specified, endpoints defined in Section 1.1 will be summarized using 
descriptive statistics, listed, and graphically presented (where appropriate). Continuous data will 
be summarized using descriptive statistics: n, mean, standard deviation (std), median, minimum, 
and maximum. The loge-transformed PK parameters based on the geometric mean will be 
summarized using geometric mean, 95% confidence interval (CI) and the between-participant 
coefficient of variance (CV), %CVb. Categorical data will be summarized as the number and 
percentage of participants in each category. 
Confidence intervals will use 95% CIs unless otherwise specified. 
It is anticipated that study participant accrual will be spread thinly across centers and summaries 
of data by center would unlikely be informative and will not, therefore, be provided. 
4.1.2. 
Baseline Definition 
For all endpoints, the baseline value will be the latest pre-dose assessment within 21 days prior 
to first dose with a non-missing value, including those from unscheduled visits. If time is not 
collected, Day 1 assessment are assumed to be taken prior to first dose and used as baseline. For 
laboratory data, baseline will be the latest non-missing pre-dose value. For PD assessment, only 
the Cycle 1 Day 1 pre-dose measurement will be used as baseline. For electrocardiogram, if 
triplicate 12-lead electrocardiograms (ECGs) are collected at the last pre-dose assessment, the 
average of the three measurements will be used as baseline record. If there are multiple 
assessments on the same day, the mean will be used as the baseline value.  
Unless otherwise stated, if baseline data is missing no derivation will be performed and baseline 
will be set to missing. 
Parameter 
Study Assessments Considered as 
Baseline 
Baseline Used in 
Data Display 
Screening 
(within 21 days 
prior to first dose) 
Day 1 (Pre-Dose) 
Efficacy 
Disease assessment 
X 
Screening visit 
Safety 


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Parameter 
Study Assessments Considered as 
Baseline 
Baseline Used in 
Data Display 
Screening 
(within 21 days 
prior to first dose) 
Day 1 (Pre-Dose) 
Laboratory 
X 
X 
Latest up to Day 1 
Vital Signs 
X 
X 
Latest up to Day 1 
ECG 
X 
X 
Latest up to Day 1 
4.2. 
Primary Endpoints Analyses 
The primary safety endpoints of this study are: 
•
Number of participants with DLTs
•
AEs and changes in clinical signs and laboratory parameters.
4.2.1. 
Definition of Endpoints 
DLT is defined as any observed toxicity in the first 21 days of treatment cycle in Part 2 Arm A 
and as any observed toxicity in the first 28 days of treatment cycle in Part 2 Arm B. 
The following events occurring within the DLT reporting period (first 21 days cycle for Arm A 
or first 28 days cycle for Arm B) will be considered a DLT if its relationship to the 
investigational agent cannot be ruled out: 
Hematologic: 
•
Grade 3 or greater febrile neutropenia lasting >48 hours despite adequate treatment
•
Grade 3 is defined as absolute neutrophil count (ANC) <1000/mm3 with a single
temperature of >38.3°C or a sustained temperature of ≥38°C for more than 1 hour
•
Grade 4 is defined as ANC <1000/mm3 with a single temperature of >38.3°C or a
sustained temperature of ≥38°C for more than one hour, with life-threatening
consequences and urgent intervention indicated
•
Grade 4 thrombocytopenia <25,000/mm3 accompanied by clinically significant
bleeding.
Non-hematologic except corneal toxicity: 
•
Any Grade 3 or greater non-hematologic toxicity (other than corneal events) which
does not resolved with appropriate supportive treatment within 48 hours
•
Any Grade 3 or greater non-hematologic laboratory value if
•
The laboratory abnormality persists for >48 h despite supportive treatment
•
The abnormality leads to hospitalization
Corneal toxicity: 
•
Grade 4 per the modified corneal grading scale (See Protocol Appendix 7).
Other organ-specific toxicity: 
•
Liver toxicity meeting pre-specified GSK liver stopping criteria


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4.2.2. 
Main Analytical Approach 
The analyses described in the following sections will be performed using the All Treated analysis 
set, as defined in Section 3, unless otherwise specified. Missing data will not be imputed. Further 
analysis details are provided below.  
4.2.2.1. 
Summary of DLT 
Any participant who received a complete infusion of GSK2857916 and at least 75% of planned 
doses of Bor/Dex or Pom/Dex by the end of C1 is considered DLT-evaluable. 
The ratio of the actual dose to the planned dose of Bor/Dex or Pom/Dex is to be calculated as the 
average of actual doseplanned dosefor each drug (Bortezomib and dexamethasone, or 
Pomalidomide and dexamethasone) administered to Cycle 1(C1). That means that subject will be 
considered as DLT-evaluable when the following formula is satisfied: 
(dosing ratio (%) for Bor +  dosing ratio (%) for Dex) /2 ≧ 75%  
(dosing ratio (%) for Pom  + dosing ratio (%) for Dex) /2 ≧ 75% 
DLT will be listed according to GSK Oncology Data Standards.  
4.2.2.2. 
Adverse Events 
AEs analyses including the analysis of AEs, SAEs, treatment emergent AEs, and other 
significant AEs will be based on GSK Core Data Standards. Details of the planned analysis are 
provided in OPS Section 2.6. AEs analyses will include On-treatment AEs unless otherwise 
specified.  
AEs will be coded using the standard Medical Dictionary for Regulatory Affairs (MedDRA) 
central coding dictionary. AEs, aside from corneal events will be graded by the investigator 
according to the National Cancer Institute – Common Toxicity Criteria for Adverse Events 
(NCI-CTCAE) (Version 4.03). Only AEs graded by NCI-CTCAE will be summarized unless 
otherwise specified. 
An overview summary of AEs, including counts and percentages of participants with any AE, 
AEs related to study intervention, Grade 3/4 AEs, Grade 3/4 AEs related to study intervention, 
AEs leading to dose reduction of study intervention, AEs leading to dose delay of study 
intervention, AEs leading to incomplete infusion, AEs leading to infusion interruption, AEs 
leading to permanent discontinuation of study intervention, any SAEs, SAE related to study 
intervention, fatal SAEs, and fatal SAEs related to study intervention will be produced. AEs 
leading to permanent discontinuation of study intervention will be summarized 
The relationship between MedDRA SOC, PT, and Verbatim Text will be displayed. 
A summary of number and percentage of participants with any AEs by maximum grade will be 
produced by PT; however ocular related AEs (corneal, keratopathy, microcyst, haze, opacity) by 
maximum grade will be summarised separately because the GSK grading scale is used for ocular 


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Page 13 of 45 
related AEs. AEs will be sorted by PT in descending order of the total incidence. The following 
algorithm for counting participants will be used in the summary: 
• 
Preferred term row: Participants experiencing the same AE preferred term several times 
with different grades will only be counted once with the maximum grade. 
• 
Any event row: Each participant with at least one AE will be counted only once at the 
maximum grade no matter how many events they have. 
Study treatment-related AEs, defined as an AE for which the investigator classified the 
relationship to study treatment as “Yes” will be summarised. A worst case scenario approach 
will be taken to handle data with missing relatedness. So the summary will include events with 
the relationship to study treatment as “Yes” or missing. The summary tables will be displayed by 
maximum grade in descending order of total incidence by PT. 
All AEs and treatment emergent AEs will be listed. In addition, a listing of participant IDs for 
each individual AE will be produced. 
4.2.2.2.1. Deaths and Serious Adverse Events 
A listing of deaths will be generated to provide participant-specific details on participants who 
died. 
All SAEs are included in the listing of all AEs. Separate supportive listings with participant-level 
details will be generated for 
• 
Fatal SAEs  
• 
Non-fatal SAEs 
4.2.2.2.2. Adverse Events of Special Interest 
The following will be considered adverse events of special interest (AESI) for the purpose of 
analyses:  
• Corneal events 
• Thrombocytopenia 
• 
Infusion related reactions 
 
The severity of AESIs other than corneal events will be graded using CTCAE version 4.03. A 
comprehensive list of MedDRA terms based on the safety review team (SRT) will be used to 
identify each type of event. Severity of corneal events associated with study intervention and 
related ophthalmic exam finding or visual acuity will be graded using GSK scale. 
Summaries of the number and percentage of participants with AESIs by PT and maximum grade 
will be provided for each type of AESIs separately. The time of onset and duration of first 
occurrence of each type of AESIs will be summarised as a continuous variable. The number and 
percentage of participants who have time of onset of first occurrence (1-21, 22-42, 43-63, >63 


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Page 14 of 45 
days for CTCAE grading of Arm A and 1-21, 22-42, 43-63, 64-105 and >105 for GSK scale 
grading of Arm A; 1-28, 28-56, >56 days for CTCAE grading of Arm B and 1-28, 29-56, 57-84, 
85-112 and >112 for GSK scale grading of Arm B) will be summarised. The number and 
percentage of participants who have duration of first occurrence (1-21, 22-42, >42 days for Arm 
A, 1-28, 29-56, >56 days for Arm B) will also be summarised. 
A summary of event characteristics will be provided, including number of participants with any 
event, number of events, number of participants with any event that is serious, number of 
participants with any event that is related to study treatment, number of occurrence (One, Two, 
Three or more), maximum grade, and the action taken for the event. The percentage will be 
calculated in two ways, one with number of participants with events as the denominator and the 
other with total number of participants as the denominator. The worst-case approach will be 
applied at participant level for the maximum grade, i.e. a participant will only be counted once as 
the worst case from all the events experienced by the participant. For actions taken to an event, a 
participant will be counted once under each action, e.g. if a participant has an event leading to 
both study treatment discontinuation and dose reduction, the participant will be counted once 
under both actions. 
Corneal events will be summarized with both CTCAE scale and GSK Scale. Corneal events with 
CTCAE scale overview will be summarized, including number of participants with events 
related to study treatment, with grade 3/4 events, with grade 3/4 events related to study 
treatment, with events leading to permanent discontinuation of study treatment, with events 
leading to dose reduction, and with events leading to dose interruption/delay. The summary for 
GSK scaled corneal events includes corneal events overview (same as CTCAE scaled summary), 
summary by grade and visit, and summary of action taken with GSK2857916.  
All AESI will be listed separately. The details of the planned displays are provided in OPS 
Section 2.6, 2.12 & 2.13 (Safety Tables, ICH Listings, and Non-ICH Listings).   
4.2.2.3. 
Clinical Laboratory Data 
Clinical laboratory tests to be performed are listed in Appendix 3, including Chemistry 
laboratory test, Haematology laboratory tests, and Urinalysis. Laboratory evaluations will be 
based on GSK Core Data Standards. The details of the planned displays are provided in OPS 
Section 2.6.  
Summary of change from baseline by scheduled visits using mean, median, standard deviation, 
minimum, and maximum will be provided. Count data will be used for automated white blood 
cell (WBC) differential. Detailed derivation of baseline assessment is specified in Section 4.1.2. 
Laboratory grades will be reported using NCI-CTCAE Version 4.03. For these gradable 
laboratory tests, summaries of worst-case grade increase from baseline grade will be provided. 
These summaries will display the number and percentage of participants with a maximum post-
baseline grade increasing from their baseline grade. Any increase in grade from baseline will be 
summarized along with any increase to a maximum grade of 3 and any increase to a maximum 
grade of 4. 


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Page 15 of 45 
Missing baseline grade will be assumed as grade 0. For laboratory tests that are graded for both 
low and high values, summaries will be done separately and labelled by direction, e.g. sodium 
will be summarised as hyponatremia and hypernatremia. 
For the laboratory tests that are not gradable by CTCAE v4.03, summaries of worst-case change 
from baseline with respect to normal range will be generated. Decreases to low, changes to 
normal or no changes from baseline, and increases to high will be summarised for the worst-case 
post-baseline. If a participant has a decrease to low and an increase to high during the same time 
interval, the participant is counted in both the “Decrease to Low” categories and the “Increase to 
High” categories. 
Separate summary tables for haematology, chemistry, and urinalysis laboratory tests will be 
produced. A separate listing of laboratory data with character values will also be provided. 
A supporting listing of laboratory data for participants with any value of potential clinical 
importance will be provided. For lab tests that can be graded, values of grade 1 or above are 
defined as values of potential clinical concern. For lab test values that cannot be graded, values 
out of the normal range are defined as values of potential clinical concern. Please refer to Section 
6.4.1 for the details of values of potential clinical importance defined in this study.  
A summary of worst case urinalysis results post-baseline relative to baseline will be generated. 
Also, a supporting listing with participant level details will be provided. 
Unless otherwise specified, the denominator in percentage calculation at each scheduled visit 
will be based on the number of participants with non-missing value at each individual visit. 
4.3. 
Secondary Endpoints Analyses 
Secondary endpoints include  
• 
GSK2857916 and cys-mcMMAF PK parameters following IV single and repeat dose 
administration as data permit (e.g., AUCs, maximum observed plasma concentration 
[Cmax], time of maximum observed plasma concentration [tmax], CL, Vss, t1/2 [single 
dose], Ceoi, trough plasma concentration [Ctrough], and Rac (Ceoi and Ctrough) [repreat 
dose]). 
• 
ADA incidence and titers after IV single and repeat dosing of GSK2857916. 
• 
Clinical activity measured as ORR and CBR which are defined as follows: 
o ORR: the percentage of participants achieving confirmed partial response or better 
(≥PR) 
o CBR: the percentage of participants with MR or better 
4.3.1. 
Pharmacokinetics 
4.3.1.1. 
Definition of Endpoints 
PK parameters will be calculated by standard non-compartmental analysis according to current 
GSK Clinical Pharmacology Modelling & Simulation (CPMS) working practices and using the 
currently supported version of WinNonLin (Currently version 8.0). 


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Page 16 of 45 
Calculation of non-compartmental parameters for the analysis will be based on actual sampling 
times. GSK2857916 (intact ADC, total antibody) and cys-mcMMAF PK parameters listed in 
Table 1 will be determined from the serum concentration-time data, as data permits, for each 
dose of GSK2857916 and for each participant: 
1) After single dose: area under the plasma concentration-time curve (AUC(0-t), AUC(0-
tau) and/or AUC(0-∞)), maximum observed plasma concentration (Cmax), time to Cmax
(tmax), last time point where the concentration is above the limit of quantification (tlast),
systemic clearance (CL), volume of distribution at steady state (Vss), terminal phase
elimination rate constant (λz), terminal phase half-life (t½). Note that the pre-Cycle 2
Day 1 will be handled as the last of Cycle 1.
2) After repeat dose: concentration at end of infusion (Ceoi) after Cycles 4, 6, 9, and 12 and
concentration pre-dose (Ctrough) prior to Cycles 4, 6, 9, and 12 for accumulation ratio
analysis.
Table 1 
Derived Pharmacokinetic Parameters 
Parameter 
Parameter Description 
AUC(0-t) 
Area under the concentration-time curve from time zero to the time of the last quantifiable 
concentration (C(t)) will be calculated using the linear trapezoidal rule for each incremental 
trapezoid and the log trapezoidal rule for each decremental trapezoid 
AUC(0-τ) 
Area under the concentration-time curve during the dosing interval 
AUC(0-∞) 
Area under the concentration-time curve extrapolated to infinity will be calculated as: 
AUC = AUC(0-t) + C(t) / lambda_z 
Cmax 
Maximum observed concentration, determined directly from the concentration-time data for 
each cycle.  For cys-mcMMAF, Cmax will not be derived when only predose and End of 
Infusion (EOI) samples were collected. 
tmax 
Time to reach Cmax, determined directly from the concentration-time data 
t½ 
Apparent terminal half-life will be calculated as: 
t½ = ln(2) / lambda_z 
tlast 
Time of last observed quantifiable concentration 
CL 
Clearance 
Vss 
Volume of distribution at steady state 
λz, 
lambda_z 
Terminal phase rate constant 
4.3.1.2. 
Main Analytical Approach 
The secondary PK analyses will be based on the PK analysis set as defined in Section 3, unless 
otherwise specified. Missing data will not be imputed. 
4.3.1.2.1. Drug concentration measures 
GSK2857916 (intact ADC and total antibody) and cys-mcMMAF concentration-time data will 
be listed for each participant and summarized by descriptive statistics and each time point for 
Arm A and Arm B separately. If the difference between the number of participants with 
measurements and the number of imputations is 2 or less or if the number of participants with 
measurements is 1, SD will not be calculated. Linear and semi-logarithmic individual plasma 


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Page 17 of 45 
concentration-time profiles and mean and median profiles (when applicable) by GSK2857916 
dose will be plotted for GSK2857916 (intact ADC and total antibody) and cys-mcMMAF. 
4.3.1.2.2. Derived PK parameters 
PK parameters defined in Section 4.3.1.1will be listed and summarized descriptively with mean, 
standard deviation, median, minimum, maximum, geometric mean, and the standard deviation of 
log-transformed parameters, CV% and 95% CI of log-transformed parameters) for Arm A and 
Arm B separately. Data display specification for derived PK parameter summaries and listings 
are provided in OPS Section 2.7 & 2.8 (Pharmacokinetics Tables & Figures). 
4.3.1.2.3. Assessment of Accumulation Ratio 
To assess the extent of accumulation following GSK2857916 repeat dosing, the observed 
accumulation ratio (R0) for GSK2857916 intact ADC, total antibody, and cys-mcMMAF will be 
determined as a ratio of Ceoi at Cycles 4, 6, 9, and 12 to Ceoi at Cycle 1 and as a ratio of 
Ctrough at Cycles 3, 5, 8, and 11 to Ctrough at Cycle 1. 
Participants must receive the same dose as Cycle 1 without delay and receive the same dose for 
the previous 4 cycles relative to the cycle of interest to be included in this analysis (i.e. with 
dosing delays of ≤ 3 days). Note that receving1.9 mg/kg of GSK2857916 on Cycle 2 is not 
considered as the dose reduction from Cycle 1 for Arm B. 
R0(Ceoi) = Ceoi(Cx) / Ceoi(C1); x=4, 6, 9, 12 
R0(Ctrough) = Ctrough(Cx) / Ctrough*(C1); x=3, 5, 8, 11 
Ctrough(Cx)=Pre-dose at Cycle(x+1) 
Ctrough*(C1)=Pre-dose at Cycle 2 Day 1 (trough of C1) 
Accumulation ratio of Ceoi and Ctrough will be summarised using descriptive statistics, 
graphically presented (where appropriate), and listed for Arm A and Arm B separately.  
Additionally, geometric mean and 95% CI will be calculated by taking the exponential for the 
mean and 95% CI of the difference in log-transformed concentration between the visit and Cycle 
1 Day 1. These parameters will be summarized and plotted. 
Details of the planned displays are provided in OPS Section 2.7 & 2.8 (Pharmacokinetics Tables 
& Figures) and will be based on GSK Data Standards and statistical principles. 
4.3.2. 
Safety 
4.3.2.1. 
Definition of Endpoints 
The secondary safety endpoint is anti-GSK2857916 (drug) binding antibody. 
4.3.2.2. 
Main Analytical Approach 
For each participant, the anti-GSK2857916 (drug) binding antibody results and titers, ADC, and 
total antibody concentration will be listed for each assessment time point. The frequency and 
percentage of participants with positive and negative anti-drug antibody will be summarised for 


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each assessment and overall for each participant separately for Arm A and Arm B. The 
conclusive results will be based on the total antibody concentration. 
4.3.3. 
Efficacy 
4.3.3.1. 
Definition of Endpoints 
The secondary efficacy endpoints are ORR and CBR. ORR is defined as the percentage of 
participants with a confirmed partial response (PR) or better (i.e. PR, very good partial response 
[VGPR], complete response [CR], and stringent complete response [sCR]) of best response, 
according to the IMWG Response Criteria [Kumar, 2016]. CBR is defined as the percentage of 
participants with a confirmed MR or better (i.e. MR, PR, VGPR, CR, and sCR) of best response, 
according to the IMWG Response Criteria [Kumar, 2016]. 
4.3.3.2. 
Main Analytical Approach 
The hierarchy of response classifications from high to low is as follows: sCR, CR, VGPR, PR, 
MR, stable disease (SD), progressive disease (PD), and not evaluable (NE). Response was 
assessed according to the IMWG Response Criteria [Kumar, 2016] (See Section 6.5). 
Unconfirmed response (without confirmation) are response assessments provided by the 
investigator. Confirmed response (with confirmation) is defined and the outline in derivation 
detailed in Table 2. For confirmed response derivations, only response assessments from the start 
of treatment up to the start of new anti-cancer therapy will be considered. Best Overall Response 
(BOR) will be derived from confirmed responses.  
The analyses will be based on the All Treated analysis set as defined in Section 3, unless 
otherwise specified.  
Table 2 
Response confirmation algorithm 
# Response at 
the First Time 
Point 
Response at Subsequent Disease 
Assessment1 
Confirmed 
Response at the 
First Time Point 
Date of 
Confirmed 
Response 
1 sCR 
sCR 
sCR 
First Time Point 
2 sCR 
CR 
CR 
First Time Point 
3 CR 
sCR/CR 
4 sCR/CR 
VGPR 
VGPR 
First Time Point 
5 VGPR 
sCR/CR/VGPR 
6 sCR/CR/VGP
R 
PR 
PR 
First Time Point 
7 PR 
sCR/CR/VGPR/PR 
8 sCR/CR/VGP
R/PR 
MR 
MR 
First Time Point 
9 MR 
sCR/CR/VGPR/PR/MR 


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10 sCR/CR/VGP
R/PR/MR 
SD 
SD 
First Time Point 
11 sCR/CR/VGP
R/PR/MR 
PD (any reason) 
OR 
No subsequent disease assessment: 
participant died or discontinued 
study or started new anti-cancer 
therapy before further adequate 
disease assessment 
SD 
First Time Point 
12 PD (due to 
reasons other 
than imaging, 
i.e.,
plasmacytoma
or bone lesion)
PD (any reason) including PD after 
initiation of new anti-cancer therapy 
OR 
No subsequent disease assessment: 
participant died due to PD before 
further adequate disease assessment 
(including death due to PD after 
initiation of new anti-cancer therapy) 
PD 
First Time Point 
13 PD (due to 
reasons other 
than imaging, 
i.e.,
plasmacytoma 
or bone lesion) 
sCR/CR/VGPR/PR/MR/SD 
OR 
No subsequent disease assessment: 
participant died due to reasons other 
than PD before further adequate 
disease assessment 
OR 
No subsequent disease assessment: 
participant discontinued study before 
further adequate disease assessment 
NE 
First Time Point 
14 sCR/CR/VGP
R/PR/MR/PD 
(due to 
reasons other 
than imaging, 
i.e.,
plasmacytoma
or bone lesion) 
No subsequent disease assessment: 
participant has not died, discontinued 
from study or (except for PD) started 
new anti-cancer therapy; but as yet has 
no further adequate disease 
assessments 
Unconfirmed 
sCR/CR/VGPR/PR/M
R/PD. 
Will be categorized 
as NE for final ORR 
analysis. 
First Time Point 
15 SD 
Any 
OR 
SD 
First Time Point 


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No subsequent disease assessment 
16 PD due to 
imaging 
(plasmacytom
a or bone 
lesion)  
Any 
OR 
No subsequent disease assessment 
PD 
First Time Point 
17 NE or missing 
Any 
OR 
No subsequent disease assessment 
NE 
First Time Point 
1.
Subsequent disease assessment is defined as the next adequate (not missing or NE) disease assessment
following the first timepoint before (or on the same date of) start of new anti-cancer therapy except for
confirmation of PD, for which PD or death due to PD after new anti-cancer therapy are considered for
confirmation of PD. No minimal time interval is required for the subsequent disease assessment, but a
different sample is required for confirmation.
•
SD does not need to be confirmed.
•
PD due to imaging (i.e., plasmacytoma or bone lesion) does not need to be confirmed.
•
Where criteria are not mutually exclusive, take the first that applies.
4.3.3.2.1. Summary Measure for BOR 
Best Overall Response (BOR) will be derived from confirmed responses. The number and 
percentage of participants with BOR in the following response categories will be summarized for 
Arm A and Arm B separately: sCR, CR, VGPR, PR, overall response (sCR+CR+VGPR+PR), 
MR, SD, PD and NE. 
4.3.3.2.2. Summary Measure for ORR and CBR 
Summary of ORR and CBR will be provided with the number and percentage of participants 
included. A two-sided exact 95% CI for ORR and CBR will also be provided. Participants with 
unknown or missing response will be treated as non-responders, i.e. these participants will be 
included in the denominator when calculating percentages of response. 
In addition, A profile plot that displays the clinical response over time with the dose of 
GSK2857916 on each cycle will be produced. Listings of investigator assessed response, 
extramedullary disease evaluation, disease assessment scan, and skeletal survey will be provided. 
Details of the planned displays are provided in OPS Section 2.5, 2.6 &2.12 (Efficacy Tables, 
Efficacy Figure and ICH Listings). 
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4.5. 
Other Safety Analyses 
4.5.1. 
Vital Signs 
Vital signs analyses will be based on GSK Core Data Standard, unless otherwise specified. Vital 
sign data include blood pressure, heart rate, and temperature. 
Vital signs data will be summarised with change from baseline (see Section 4.1.2) for detailed 
baseline derivation) as continuous variables. 
In addition, vital sign values will be categorized as follows: 
•
Systolic blood pressure (mmHg):
Grade 0 (<120), Grade 1 (120-139), Grade 2 (140-159) and Grade 3 (≥160)
•
Diastolic blood pressure (mmHg):
Grade 0 (<80), Grade 1 (80-89), Grade 2 (90-99), and Grade 3 (≥100)
•
Heart rate (beats/min):
<60, 60-100, and >100
•
Temperature (°C):
≤35, >35-<38, ≥38
Summaries of worst-case changes in vital signs from baseline with respect to the categories 
defined above will be performed.  
Listings with vital signs values as well as participants with abnormalities of potential clinical 
importance and grade will be provided.  
4.5.2. 
Electrocardiograms 
ECG data analyses will be based on GSK Core Data standards, unless otherwise specified. ECG 
data will include heart rate, PR, RR interval, QRS, QT and QTcF (QTc values based on 
Fridericia formula) intervals. Baseline QTcF value is determined by Day 1 pre-dose QTcF result 
(either a single result or the mean of triplicate resulted). If Day 1 pre-dose value is not available, 
the screening ECG results should be used. QTcF values will be rounded to the integer and 
categorized into the following ranges: Grade 0 (<450), Grade 1 (450-480), Grade 2 (481-500), 
and Grade 3 (≥501) and summarized. 
The ECG results, increase in QTcF, and amount of increase from baseline value will be 
summarised. 
Listings of abnormal ECG findings and a listing of ECG values including Potential Clinical 
Importance will be provided. Potential clinical significance ranges are provided in Section 6.4.1. 
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4.5.3. 
Ocular Exams 
Ophthalmic exams are scheduled at screening, during the study, end of treatment (EOT) visit, 
and follow-up period. The ocular findings from ophthalmic exams will be analysed as described 
below. 
1. From baseline to EOT visit, the following analysis will be performed:
Best corrected visual acuity (BCVA): BCVA (logMAR score) at baseline, EOT visit, and last 
follow-up visit as well as worst and most frequent category (definite worsen, possible worsen, 
and no change/improved) of change from baseline will be summarised by eye (R/L) and 
participant (worse eye and better eye). BCVA for participants with corneal finding will also 
be provided. The logMAR score is calculated as: 
logMAR score = -1* (log10(Landolt ring value)) 
2. From EOT visit to last follow-up visit, the following analyses will be performed to assess the
change in corneal findings after discontinuation of study treatment, for participants (worse eye)
with exam finding at EOT visit worse than baseline.
a.
Summary of change (worsening, no change, improvement) from EOT to last follow-
up visit based on categories defined below by eye (R/L) and participant (worse eye).
b. Summary of number (%) of eyes and participants (worse eye) that resolve (improve
to baseline level or better based on categories defined below), and descriptive
summary of time from EOT visit to resolution among eyes and participants (worse
eye) that resolved.
The parameters included in analyses are listed below: 
1. BCVA change from baseline in log MAR scale (< 0.12, ≥ 0.12 to < 0.3, ≥ 0.3). This
parameter is included in both analyses detailed above.
2. Corneal epithelium (Normal/Abnormal), Punctate Keratopathy
(None/Mild/Moderate/Severe), Microcystic edema (No/Yes), Microcystic without edema
(No/Yes), Subepithelial haze (No to Yes), Corneal neovascularization (No to Yes),
Stroma (Normal/Abnormal), Active opacity (No/Yes), Active edema (No/Yes). These
parameters are included only in analysis a) described above.
All summary and shift tables will be provided by eye (R/L) and worse eye or better eye. If both 
eyes are diagnosed as abnormal, participant is counted as abnormal (yes, present, or others). 
The ocular exam results will be listed. The details of the planned displays are provided in OPS 
Section 2.6, 2.12, & 2.13 (Safety Tables, ICH Listings, and Non-ICH Listings). 
4.5.4. 
Left Ventricular Ejection Fraction 
Left ventricular ejection fraction (LVEF) data will be analysed based on GSK Oncology Data 
Standard. LVEF data are collected at screening and end of treatment visit. Post-baseline 


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assessments that used the same method of Echocardiogram (ECHO) as the baseline assessments 
will be used to derive the change from baseline. Absolute change from baseline in LVEF will be 
summarized by worst case post-baseline and by EOT. The change from baseline will also be 
categorized as follows: 
•
No change or any increase
•
Any decrease
o
>0-<10 decrease
o
10-19 decrease
o
≥20 decrease
o
≥10 decrease and ≥ lower limit of normal (LLN)
o
≥10 decrease and < LLN
o
≥20 decrease and ≥ LLN
o
≥20 decrease and < LLN
LVEF results will be listed with participant level details, including absolute change from 
baseline. 
4.5.5. 
Other Safety Measures 
The medical conditions data for participants with liver stopping events will be listed. The 
substance use data for participants with liver stopping events will be listed. 
Eastern Cooperative Oncology Group (ECOG) performance status is collected at baseline and 
post-baseline scheduled visits and all collected data will be listed based on GSK Oncology Data 
Standard.  
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be recorded as an AE or SAE as 
described in the protocol. If participants become pregnant while on the study, the information 
will be included in the narrative and no separate table or listing will be produced. 
The safety analyses will be based on the All Treated Analysis Set as defined in Section 3, unless 
otherwise specified. 
4.5.6. 
Extent of Exposure 
Extent of exposure to GSK2857916, bortezomib, dexamethasone, and pomalidomide will be 
summarised. 
The number of cycles administered to study treatment will be summarised with mean, median, 
standard deviation, minimum, and maximum. The number and percentages of participants who 
received a given number of cycles (<=4, >4 cycles) will be reported. Note that the cycle will not 
be counted when the administration is interrupted/delayed. 
Cumulative actual dose (sum of dose at each cycle) and dose intensity per cycle (mg/kg/cycle) 
will be summarised using mean, median, standard deviation, minimum, and maximum by 
overall. The dose intensity (mg/kg/3 weeks) for Arm A, which is calculated as the cumulative 


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actual dose (mg/kg) divided by expected duration of exposure in 3 weeks  (Last Dose date – First 
Dose date + 21)/21 and the dose intensity (mg/kg/4 weeks) for Arm B, which is calculated as the 
cumulative actual dose (mg/kg) divided by expected duration of exposure in 4 weeks  (Last Dose 
date – First Dose date + 28)/28 will also be summarised. A by-participant summary listing of 
data on exposure to all study treatments will be produced. 
Dose reductions will be summarised by number of reductions and reasons for reductions. Dose 
delays will be summarised by number of delays, reasons for the delays, and delay duration 
(days). The number and percentage of the delays for duration intervals of 1-21, 22-42, and >42 
days for Arm A, of 1-28, 29-56, and >56 days for Arm B will be computed. Time to first delay 
will be summarised; first delay is defined as the first dose delay or first dose restarted after 
skipped dosing. Primary reasons for dose reductions and dose delays will also be summarised by 
overall. 
Duration of delays for GSK2857916 is defined as period from the expected start date of dose to 
actual start date of current dose. Calculation: (actual start date of current dose - expected start 
date of dose). For Arm A, expected start date of dose = actual start date of previous dose + 21. 
For Arm B, expected start date of dose = actual start date of previous dose + 28. 
The summaries of dose modifications will be provided. All the dose reductions, infusion 
interruptions, incomplete infusions and dose delays will be listed. 
The duration of exposure to GSK2857916, bortezomib, dexamethasone, and pomalidomide(from 
first day to last day of treatment) will be calculated and summarised using mean, median, 
standard deviation, minimum, and maximum.  
4.6. 
Other Analyses 
4.6.1. 
Population Pharmacokinetic (POPPK) Analyses 
The primary goal of this analysis is to characterize the population pharmacokinetics of 
GSK2857916 and associated analytes after intravenous of GSK2857916 in participants with 
multiple myeloma, as data permit. The influence of participant demographics, baseline 
characteristics, including disease activity, and co-medication on the pharmacokinetics of 
GSK2857916 in this population may be investigated. The individual participant PK parameters 
may be estimated and documented for the purposes of any subsequent exposure-response 
(PK/PD) analyses. The analysis may be performed by GSK CPMS and reported separately. 
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4.7. 
Interim Analyses 
An interim analysis may be conducted when the last participant within any arm in Part 2 has 
completed at least one cycle of the combination treatment. 
4.8. 
Planned Analyses 
A primary analysis will be conducted by the data cut-off performed after both EOT and the 
completion of AE and SAE collection (i.e., 70 days after the last dose of study treatment). The 
later of the primary analyses for Arm A (Bor/Dex) and Arm B (Pom/Dex) in Part 2 will be the 
final analysis for the study. See Section 4.2, Section 4.3, and Section 4.4 for all planned analysis 
for this study. 
4.9. 
Changes to Protocol Defined Analyses 
There were no changes or deviations to the originally planned statistical analysis specified in the 
protocol amendment 6 (Dated:10-Feb-2023). 
5.
SAMPLE SIZE DETERMINATION
The sample size planned for this study arises from the predefined criteria for dose escalation and 
is not driven by statistical considerations. 
The maximum number of participants for Part 2 will be up to 12, up to 6 participants each for 
Arm A and Arm B based on the 3 + 3 designs. 
6.
SUPPORTING DOCUMENTATION
6.1. 
Appendix 1 Study Population Analyses 
The study population analyses will be based on All Treated analysis set as defined in Section 3, 
unless otherwise specified. The analyses will also be performed for Arm A and Arm B 
separately. 
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Study population analyses including participant disposition, protocol deviations, participant 
demographic and baseline characteristic, prior and concomitant medications, anti-cancer 
therapies, and exposure and treatment modification will be based on GSK Core Data Standards. 
Details of the planned displays are presented in OPS section 2.4. 
6.1.1. 
Participant Disposition 
A summary of the number of participants in each of the analysis sets described in Section 3 will 
be provided. In addition, a listing of participants excluded from analysis populations will also be 
provided. 
A summary of participant status and reasons 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. Reasons for study withdrawal will be presented in the 
order they are displayed in the electronic case report form (eCRF). 
A summary of study treatment status will be provided. This display will show the number and 
percentage of participants who 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. Besides, the listing will also show participants who completed the 
study and move to PACT phase. 
6.1.2. 
Demographic and Baseline Characteristics 
The demographic characteristics (e.g., age, race, ethnicity, sex, baseline height, baseline body 
weight and baseline body mass index (BMI) calculated as body weight in kilograms divided by 
squared height in m2) will be summarised and listed. Age, height, weight, and BMI will be 
summarised using the mean, standard deviation, minimum, median, and maximum. The count 
and percentage will be computed for sex and ethnicity. 
Disease characteristics at initial diagnosis (e.g. time since initial diagnosis in years, stage at 
initial diagnosis, date of initial diagnosis) and screening will be listed. 
Summary of disease characteristics at screening will be provided. Disease characteristics for 
multiple myeloma participants at screening, including stage, lines of prior therapy regimens, type 
of multiple myeloma, myeloma light chain and myeloma immunoglobulin will be summarised 
and listed.  
Prior and current medical conditions will be listed and current medical conditions will be 
summarised. 
Genetic characteristics for multiple myeloma participants at screening will be summarised and 
listed. Cytogenetic risk for multiple myeloma participants at screening will be summarised. A 
participant is considered as having high cytogenetic risk if the participant has any of the 
following cytogenetics: t(4;14), 17p13del, t(14;16). 
Substance use, including smoking history and alcohol use, will be listed. 


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Prior and follow-up anti-cancer therapy will be coded using the GSK Drug code dictionary. A 
listing of prior anti-cancer therapy will show the relationship between Anatomical Therapeutic 
Chemical (ATC) Level 1 and verbatim text.  
Anti-cancer radiotherapy will be listed. Prior, on treatment, and follow-up cancer and non-cancer 
related surgeries will also be listed. A listing of Stem Cell Transplant will be provided. 
6.1.3. 
Protocol Deviations 
Important protocol deviations related to study inclusion/exclusion criteria, conduct of the trial, 
patient management, or patient assessment will be summarised and all protocol deviations, 
including both major and minor, will be listed. The classification of important protocol 
deviations includes AE/SAE, disallowed devices, disallowed medications, inclusion/exclusion 
criteria, informed consent, IP administration/study treatment, procedures/tests, and withdrawal 
criteria. The protocol deviation terms are detailed in the Protocol Deviation Specification. 
Protocol deviations will be tracked by the study team throughout the conduct of the study in 
accordance with the Protocol Deviation Specification. 
o
Data will be reviewed prior to database lock to ensure all important deviations are
captured and categorised on the protocol deviations dataset.
o
This dataset will be the basis for the summaries and listings of protocol deviations.
A separate summary and listing of all inclusion/exclusion criteria deviations will also be 
provided. This summary will be based on data as recorded on the inclusion/exclusion page of the 
eCRF. 
There is no Per-Protocol Population for this study. Protocol deviations will not be used to 
determine membership in any particular study population for this study. 
6.1.4. 
Prior and Concomitant Medications 
Concomitant medications will be coded using GSK Drug coding dictionary and listed. ATC 
classification Level 1 (Body System) information will be included in the dataset created but will 
not appear on the listing. 
Blood products or blood supportive care products with onset date within the on-treatment 
window will be included in the listings. Administration of on-treatment stem cell mobilization 
products will also be provided in a listing. 
Prior medications will be listed. 
6.1.5. 
Additional Analyses Due to the COVID-19 Pandemic 
A standardized MedDRA Query (SMQ) will be used to identify all COVID-19 AEs. 
The number of participants with suspected, probable, and confirmed COVID-19 infections will 
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The details of the planned displays are provided in OPS Section 2.6 Safety Tables. 
6.2. 
Appendix 2 Clinical Laboratory Tests 
The tests detailed in Table 3 will be performed by the local laboratory. 
Table 3 
List of Clinical Laboratory Tests 
Hematology1 
Platelet Count 
RBC Indices: 
Automated WBC Differential: 
Red blood cell (RBC) Count 
Mean corpuscular volume (MCV) 
Neutrophils 
White blood cell (WBC) Count 
(absolute) 
Mean corpuscular hemoglobin (MCH) 
Lymphocytes 
Reticulocyte Count 
Mean corpuscular hemoglobin 
concentration (MCHC) 
Monocytes 
Hemoglobin 
Eosinophils 
Hematocrit 
Basophils 


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Table 3 
List of Clinical Laboratory Tests (cont.) 
PK/ADA  
Pharmacokinetics (PK)2 
Anti-Drug Antibodies (ADA)2, 3 
Optional Testing 
Genetics2 
Disease Evaluation Laboratory Tests 
Urine Protein Electrophoresis 
(UPEP)1 
urine Immunofixation1 
24-hour urine 
collection for M-
protein1 
Calcium corrected for albumin 
(serum)
1 
Serum Protein Electrophoresis 
(SPEP)1 
Serum M-protein 
calculation1 
Serum 
Immunofixation1 
Beta2 macroglobulin1 
Serum Kappa, lambda free light 
chain (LC), Free light chain 
(FLC) ratio1 
IgG, IgA, IgM. 
IgD and IgE only in 
participants with IgD or IgE 
myeloma 
  
 
Bone Marrow Aspiration/Biopsy 
Bone marrow for disease assessment1 
Bone marrow biopsy to confirm sCR by IHC1 
Bone marrow for FISH testing5 
1. To be performed at local laboratory.   
Clinical Chemistry1 
Blood urea nitrogen 
(BUN) 
Potassium 
Aspartate 
aminotransferase (AST) 
Total and direct bilirubin 
Creatinine   
Chloride 
Alanine 
aminotransferase (ALT) 
Uric Acid 
Glucose 
Spot urine (albumin / 
creatinine ratio) 
Gamma glutamyl 
transferase (GGT) 
Albumin  
Sodium  
Calcium  
Alkaline phosphatase 
(ALP) 
Total Protein  
Magnesium  
Phosphorous  
Creatine kinase (CK) 
Lactate dehydrogenase (LDH) 
Estimated Glomerular 
filtration rate (eGFR) 
 
 
 
Urine1 
Routine Urine Dipstick (Urinalysis required if blood or protein is detected by dipstick) 
Specific gravity 
pH, glucose, protein, blood and ketones by dipstick 
Microscopic examination (if blood or protein is abnormal) 
Other Safety 
C-reactive protein (CRP)1 
Troponin I or T4 
B-type natriuretic peptide (BNP)4 
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3. Not needed at screening
4. If not available from local laboratory, it can be performed at central laboratory.
5. FISH testing at least for: t(4;14), t(14;16), 17p13del. BM samples from within 60 days prior to first dose are acceptable for
FISH analysis.
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6.3. 
Appendix 3 Schedule of Activities (SoA) 
Prefer to Protocol Section 1.3 Table 2 and Table 3 for Schedule of Activities for Part 2. 
 
 


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6.4. 
Appendix 4 Data Derivations Rule 
6.4.1. 
Criteria for Potential Clinical Importance 
6.4.1.1. 
Laboratory Values 
Reference ranges for all laboratory parameters collected throughout the study are provided by the 
laboratory. A laboratory value that is outside the reference range is considered either high 
abnormal (value above the upper limit of the reference range) or low abnormal (value below the 
lower limit of the reference range). Note: a high abnormal or low abnormal laboratory value is 
not necessarily of clinical concern. The laboratory reference ranges will be provided on the 
listings of laboratory data. Clinical laboratory test results outside of the reference range will be 
flagged in the listings. 
To identify laboratory values of potential clinical importance, NCI-CTCAE Version 4.03 will be 
used to assign grades to the relevant laboratory parameters. NCI-CTCAE v4.03 can be found at 
http://ctep.cancer.gov/reporting/ctc.html. 
For laboratory data which are not listed in the NCI-CTCAE v4.03, a summary of values outside 
the normal range will be provided. 
6.4.1.2. 
ECG 
Potential clinical importance ranges for ECG values are listed below. 
 
ECG Parameter 
Units 
Clinical Concern Range  
Low          Upper 
Absolute 
QTc Interval 
msec 
                  >480 
Change from baseline 
QTc Interval 
msec 
                  >30 
6.4.1.3. 
Vital Signs 
For vital signs, the most updated IDSL standard up to the SAP effective date will be followed. 
6.4.2. 
Study Phases 
Assessments and events will be classified according to the time of occurrence relative to 
date/time of first dose of study treatment. 
Study Phase 
Definition 
Pre-Treatment  
Date ≤ Study Treatment Start Date 
On-Treatment 
Study Treatment Start Date < Date 
On-Treatment AEs 
Study Treatment Start Date < Date ≤ Study Treatment Stop Date + 70 days 
 
For assessment or event on the first dosing day, whether it is Pre-Treatment or On-Treatment 
should be based on time if available. If time is not available, the first dosing day (Day 1) is 
considered Pre-Treatment for ECOG, ECG, vital signs, liver events, lab tests, cardiac scan, and 
other safety domains, and On-Treatment for AEs and concomitant medications. 


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6.4.2.1. 
Study Phases for Concomitant Medication and Blood and Blood Supportive 
Care Product 
Concomitant Medication and Blood and Blood Supportive Care and Stem Cell Mobilization 
Product start and end dates will be assigned to study time periods in relation to first dose of study 
treatment as defined below. The start date references time flag variables and end date reference 
time flag variables will be added to the concomitant medications and blood and blood supportive 
products datasets, respectively. 
 
• Start relative to treatment: Assign to 'BEFORE' if start date is prior to study treatment 
start date or if participant has not taken any study treatment or (start date is missing and 
end date is before study treatment start date). Else assign to 'DURING' if the start date 
falls into the on-treatment period as defined above or if participant is ongoing (not all 
study treatment discontinuation records completed) or start date is missing. Else assign to 
'AFTER' if start date is after the last study day.  
• End relative to treatment: Assign to 'BEFORE' if end date is prior to study treatment 
start date or if participant has not taken any study treatment. Else assign to 'DURING' if 
start date falls into the on-treatment period or if participant is ongoing (not all study 
treatment discontinuation records completed) or (end date is missing and start relative to 
treatment not 'AFTER'). Else assign to 'AFTER' if start date is after the last study day or 
(end date is missing and start relative to treatment='AFTER'). 
 
Only on-treatment blood and blood supportive care and stem cell mobilization products that start 
after the start of study treatment are included in the Blood Products and Blood Supportive Care 
Product and Stem Cell Mobilization Products will be listed. Therefore, for listings include blood 
and blood supportive care product records where start relative to treatment in ('DURING') and 
end relative to treatment in ('DURING', 'AFTER').  
 
Concomitant medication starts relative to treatment and ends relative to treatment flags are used 
to select data to include in the Concomitant Medication summaries as follows: 
 
• Summary of Concomitant Medications: This summary will contain medications including 
those with start date prior to study treatment start date and continue (missing end date or end 
date after study treatment start date) on therapy. Note that any medications with start date and 
end date prior to study treatment start date will be excluded. In addition, any medication that 
was started during post-therapy will be excluded. Include concomitant medication records 
where start relative to treatment in ('BEFORE', 'DURING') and end relative to treatment in 
('DURING', 'AFTER'). 
6.4.3. 
Study Day and Reference Dates 
Study Day 
• 
Calculated as the number of days from First Dose Date: 
• 
Ref Date = Missing      → Study Day = Missing  
• 
Ref Date < First Dose Date → Study Day = Ref Date – First Dose Date 
• 
Ref Data ≥ First Dose Date → Study Day = Ref Date – (First Dose Date) + 1     


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6.4.4. 
Assessment Window  
No assessment window will be applied in this study. 
6.4.5. 
Treatment Emergent Flag for Adverse Events  
Flag 
Definition 
Treatment 
Emergent 
• 
Study Treatment Start Date <= AE Start Date <= Start of Anti-cancer Therapy  
• 
AE Start Date is missing. 
Notes: Time of study treatment dosing and start/stop time of AEs should be considered, if 
collected. 
6.4.6. 
Multiple measurements at One Analysis Time Point 
In general, mean of the measurements will be calculated and used in any derivation of summary 
statistics but if listed, all data will be presented. For example, when triplicate ECG assessments 
are taken, mean of the measurement will be calculated first and summary statistics will be based 
on the calculated mean. This will apply to both baseline and post baseline assessment. 
Participants having both high and low values for normal ranges an any post-baseline visit for 
safety parameters will be counted in both the high and low categories of “Any visit post-
baseline” row of related summary tables. This will also be applicable to relevant potential 
clinical importance summary tables. 
6.4.7. 
Handling of Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant listing displays. 
• 
Imputed partial dates will not be used to derive study day, duration (e.g. duration of 
AEs), or elapsed time variables. In addition, imputed dates are not used for deriving 
the last contact date in the overall survival analysis dataset. 
• 
Imputed dates will not be displayed in listings. However, where necessary, display 
macros may impute dates as temporary variables for the purpose of sorting data in 
listings only. In addition, partial dates may be imputed for ‘slotting’ data to study time. 
Adverse 
Events 
• 
The eCRF allows for the possibility of partial dates (i.e. only month and year) to be 
recorded for AE start and end dates; that is, the day of the month may be missing. 
Partial dates for AE recorded in the CRF will be imputed using the following 
conventions: 
Missing start day 
First of the month will be used unless this is before the start 
date of study treatment; in this case the study treatment start 
date will be used and hence the event is considered On-
treatment as per Section 6.4.5 Treatment Emergent Flag for 
Adverse Events . 
Missing start day 
and month 
No Imputation 


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Element 
Reporting Detail 
Missing end day  
A '28/29/30/31' will be used for the day (dependent on the 
month and year), unless this is after the stop date of study 
treatment; in this case the study treatment stop date will be 
used. 
Missing end day 
and month 
No Imputation 
Completely 
missing start/end 
date 
No imputation 
Concomitant 
Medications/M
edical History 
• 
Partial dates for any concomitant medications recorded in the CRF will be imputed 
using the following convention: 
 
Missing start day 
Set start date = 1st of month. 
Missing start day 
and month 
A '01' will be used for the day and 'Jan' will be used for the 
month 
Missing end day 
A '28/29/30/31' will be used for the day (dependent on the 
month and year).  
Missing end day 
and month 
A '31' will be used for the day and 'Dec' will be used for the 
month. 
Completely missing 
start/end date 
No imputation 
 
 
 


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6.5. 
Appendix 5 International Myeloma Working Group Uniform 
Response Criteria for Multiple Myeloma 
Response 
IMWG Criteria 
Stringent complete 
response (sCR) 
• 
Complete response as defined below plus normal FLC ratio1 and absence of clonal 
cells in bone marrow biopsy by immunohistochemistry (κ/λ ratio ≤4:1 or ≥1:2 for κ 
and λ patients, respectively, after counting ≥100 plasma cells)2 
Complete response 
(CR) 
• 
Negative immunofixation on the serum and urine and disappearance of any soft 
tissue plasmacytomas and < 5% plasma cells in bone marrow3 
Very good partial 
response (VGPR) 
• 
Serum and urine M-protein detectable by immunofixation but not on electrophoresis 
or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 h 
Partial response (PR) 
• 
≥50% reduction of serum M-protein plus reduction in 24 h urinary M-protein by 
≥90% or to <200 mg per 24 h; 
• 
If the serum and urine M-protein are unmeasurable, a ≥50% decrease in the 
difference between involved and uninvolved FLC levels is required in place of the 
M-protein criteria; 
• 
If serum and urine M-protein are unmeasurable, and serum-free light assay is also 
unmeasurable, ≥50% reduction in plasma cells is required in place of M-protein, 
provided baseline bone marrow plasma-cell percentage was ≥30%. In addition to 
these criteria, if present at baseline, a ≥50% reduction in the size (SPD)4 of soft 
tissue plasmacytomas is also required 
Minimal response 
(MR) 
• 
≥25% but ≤49% reduction of serum M-protein and reduction in 24-h urine M-protein 
by 50–89%. In addition to the above listed criteria, if present at baseline, a ≥50% 
reduction in the size (SPD)4 of soft tissue plasmacytomas is also required 
Stable 
Disease (SD) 
• 
Not recommended for use as an indicator of response; stability of disease is best 
described by providing the time-to-progression estimates. Not meeting criteria for 
complete response, very good partial response, partial response, minimal response, 
or progressive disease 
Progressive disease 
(PD)5,6  
Any one or more of the following criteria: 
• 
Increase of 25% from lowest confirmed response value in one or more of the 
following criteria: 
    - Serum M-protein (absolute increase must be ≥0·5 g/dL); 
    - Serum M-protein increase ≥1 g/dL, if the lowest M component was ≥5 g/dL; 
    - Urine M-protein (absolute increase must be ≥200 mg/24 h); 
• 
In participants without measurable serum and urine M-protein levels, the difference 
between involved and uninvolved FLC levels (absolute increase must be >10 
mg/dL); 
• 
In participants without measurable serum and urine M-protein levels and without 
measurable involved FLC levels, bone marrow plasma-cell percentage irrespective 
of baseline status (absolute increase must be ≥10%); 


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• 
Appearance of a new lesion(s), ≥50% increase from nadir in SPD4 of >1 lesion, or 
≥50% increase in the longest diameter of a previous lesion >1 cm in short axis; 
• 
≥50% increase in circulating plasma cells (minimum of 200 cells per μL) if this is the 
only measure of disease 
Relapse 
Clinical relapse requires one or more of: 
• 
Direct indicators of increasing disease and/or end organ dysfunction (CRAB 
features) related to the underlying clonal plasma-cell proliferative disorder. It is not 
used in calculation of time to progression or progression-free survival but is listed as 
something that can be reported optionally or for use in clinical practice; 
• 
Development of new soft tissue plasmacytomas or bone lesions (osteoporotic 
fractures do not constitute progression); 
• 
Definite increase in the size of existing plasmacytomas or bone lesions. A definite 
increase is defined as a 50% (and ≥1 cm) increase as measured serially by the 
SPD§§ of the measurable lesion; 
• 
Hypercalcaemia (>11 mg/dL); 
• 
Decrease in haemoglobin of ≥2 g/dL not related to therapy or other non-myeloma-
related conditions; 
• 
Rise in serum creatinine by 2 mg/dL or more from the start of the therapy and 
attributable to myeloma; 
• 
Hyperviscosity related to serum paraprotein 
Overall Responders: PR, VGPR, CR, sCR 
Clinical Benefit Rate: Overall responders + MR 
Adapted from Kumar et.al. Lancet Oncol 2016; 17: e328–46 
1 All recommendations regarding clinical uses relating to serum FLC levels or FLC ratio are based on results obtained with 
the validated Freelite test (Binding Site, Birmingham, UK).  
2 Presence/absence of clonal cells on immunohistochemistry is based upon the κ/λ/L ratio. An abnormal κ/λ ratio by 
immunohistochemistry requires a minimum of 100 plasma cells for analysis. An abnormal ratio reflecting presence of an 
abnormal clone is κ/λ of >4:1 or <1:2.  
3 Special attention should be given to the emergence of a different monoclonal protein following treatment, especially in the 
setting of participants having achieved a conventional complete response, often related to oligoclonal reconstitution of the 
immune system. These bands typically disappear over time and in some studies have been associated with a better outcome. 
Also, appearance of monoclonal IgG κ in participants receiving monoclonal antibodies should be differentiated from the 
therapeutic antibody.  
4 Plasmacytoma measurements should be taken from the CT portion of the PET/CT, or MRI scans, or dedicated CT scans 
where applicable. For participants with only skin involvement, skin lesions should be measured with a ruler. Measurement of 
tumour size will be determined by the SPD. 
5 Positive fixation alone in a participant previously classified as achieving a complete response will not be considered 
progression. For purposes of calculating time to progression and progression-free survival, participants who have achieved a 
complete response and are MRD-negative should be evaluated using criteria listed for progressive disease. Criteria for 
relapse from a complete response or relapse from MRD should be used only when calculating disease-free survival.  
6 In the case where a value is felt to be a spurious result per physician discretion (e.g. a possible laboratory error), 


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that value will not be considered when determining the lowest value. 


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6.6. 
Appendix 6 Abbreviations 
Abbreviation 
Description 
ADA 
Anti-drug antibody 
ADaM 
Analysis Data Model 
ADC 
Antibody Drug Conjugate 
AE 
Adverse Event 
AESI 
Adverse events of special interest 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
BCVA 
Best corrected visual acuity 
BMI 
Body mass index 
BNP 
B-type natriuretic peptide 
BOR 
Best Overall Response 
Bor/Dex 
Bortezomib and Dexamethasone 
BUN 
Blood urea nitrogen 
C1D1 
Cycle 1 Day 1 
C2D1 
Cycle 2 Day 1 
CBR 
Clinical Benefit Rate 
CDISC 
Clinical Data Interchange Standards Consortium 
CI 
Confidence Interval 
CK 
Creatine kinase 
CL 
Clearance 
Cmax 
Maximum observed plasma concentration 
CPMS 
Clinical Pharmacology Modelling & Simulation 
CR 
Complete Response 
CRP 
C-reactive protein 
Ctrough 
Trough plasma concentration 
CV 
Coefficient of Variation 
Cys-mcMMAF 
Cysteine maleimidocaproyl monomethyl auristatin F 
DBF 
Database Freeze 
DCO 
Data cut-off 
DLT 
Drug Limiting Toxicity 
ECHO 
Echocardiogram 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group  
eCRF 
Electronic Case Record Form 
eGFR 
Estimated glomerular filtration rate 
EOI 
End of Infusion 
EOT 
End of Treatment 
EOS 
End of Study 
FDA 
Food and Drug Administration 
FDAAA 
Food and Drug Administration Clinical Results Disclosure Requirements 
FLC 
Free light chain 
GGT 
Gamma glutamyl transferase 
GSK 
GlaxoSmithKline 


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Abbreviation 
Description 
ICH 
International Conference on Harmonization 
IDSL 
Integrated Data Standards Library 
IHC 
Immunohistochemistry 
IMWG 
International Myeloma Working Group 
IV 
Intravenous(ly) 
LC 
Light chain 
LDH 
Lactate dehydrogenase 
LLN 
Lower limit of normal 
LVEF 
Left ventricular ejection fraction 
MCV 
Mean corpuscular volume 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MedDRA 
Medical Dictionary for Regulatory Affairs 
MR 
Minimal Response 
NE 
Not Evaluable 
NCI-CTCAE 
the National Cancer Institute – Common Toxicity Criteria for Adverse Events 
NQ 
Non-quantifiable 
OPS 
Output and Programming Specification 
ORR 
Overall Response Rate 
PACT 
Post analysis continued treatment 
PD 
Pharmacodynamic 
PD 
Progressive Disease 
PK 
Pharmacokinetic 
Pom/Dex 
Pomalidomide and Dexamethasone 
PopPK 
Population PK 
PR 
Partial Response 
PY 
Person Year 
Q3W 
Once every 3 weeks 
Q4W 
Once every 4 weeks 
QTcF 
Frederica’s QT Interval Corrected for Heart Rate 
RAP 
Reporting & Analysis Plan 
RBC 
Red blood cells 
SAC 
Statistical Analysis Complete 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
 
 
sCR 
Stringent Complete Response 
SD 
Stable Disease 
SMQ 
Standardized MedDRA Query 
SoA 
Schedule of activities 
SoC 
Standard of Care 
SOC 
System Organ Class 
SPEP 
Serum protein electrophoresis 
SRT 
Safety review team 
T1/2 
Terminal phase half-life 
TFL 
Tables, Figures & Listings 
tlast 
Time of last quantifiable concentration 
Tmax 
Time of maximum observed plasma concentration 
CCI


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Abbreviation 
Description 
UPEP 
Urine protein electrophoresis 
VGPR 
Very Good Partial Response 
vss 
Volume of distribution at steady state 
WBC 
White blood cells 
λz 
Terminal phase elimination rate constant 
 
 
 
 


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Trademarks 
Trademarks of the GlaxoSmithKline Group 
of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
N/A 
 
WinNonlin 
 
 
 
 


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Page 44 of 45 
7. 
REFERENCES 
GlaxoSmithKline Document Number RPS-CLIN-050928 Study ID 207504. A Phase I Open-
Label, Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, 
Pharmacodynamics, Immunogenicity and Clinical Activity of the Antibody Drug Conjugate 
GSK2857916 in Japanese Participants with Relapsed/Refractory Multiple Myeloma. Report Date 
10-Feb-2023. 
Kumar S, Paiva B, Anderson KC, et al. International Myeloma Working Group consensus 
criteria for response and minimal residual disease assessment in multiple myeloma. The Lancet 
Oncology. 2016;17: e328-e346.